Clinical Review

Clinical awareness of cancers associated with Camp Lejeune water contamination exposure remains limited despite legal and policy advances. Gaps persist in early symptom recognition and timely diagnostic evaluation before a definitive cancer diagnosis among exposed personnel. This may represent missed opportunities for earlier identification of volatile organic compounds (VOCs)-related cancers and for less invasive treatment options for veterans in this high-risk population.

Federal health care practitioners (HCPs), especially those in primary care and internal medicine, are uniquely positioned to bridge this gap. By improving the recognition of symptoms, pertinent physical examination findings, and implementing a diagnostic screening panel, HCPs can support accurate diagnoses and facilitate earlier treatment to improve health and quality of life for this population.

From 1953 to 1985, as many as 1 million military personnel, civilian workers, and their families stationed at US Marine Corps Base Camp Lejeune were unknowingly exposed to toxic and carcinogenic chemicals in drinking and bathing water.¹ Three of the 8 main water sources on base were contaminated with VOCs, which are associated with multiple cancers.^1-3

The US Department of Veterans Affairs (VA) recognizes 15 conditions associated with Camp Lejeune contaminated water exposure for VA benefits, including 10 cancers: adult leukemia; aplastic anemia and other myelodysplastic syndromes (MDS); bladder, esophageal, kidney, liver, breast (male and female), and lung cancers; multiple myeloma; and non-Hodgkin lymphoma (NHL).⁴

BACKGROUND

Established in 1942, Camp Lejeune is an important Marine Corps training installation. Between 1953 and 1985, multiple on-base water systems were contaminated with VOCs, including trichloroethylene (TCE), perchloroethylene (PCE), benzene, and vinyl chloride, due to improper waste disposal and industrial runoff from on- and off-base sources.⁵ Tarawa Terrace water treatment plant (WTP) was contaminated primarily with PCE from November 1957 to February 1987. Hadnot Point WTP was contaminated with TCE from August 1953 to December 1984, along with PCE, and benzene, toluene, ethylbenzene, and xylene (BTEX). Holcomb Boulevard WTP, established in 1972, was contaminated with TCE from June 1972 to February 1985.² These contaminants entered the drinking and bathing water supply over decades, and exposure often occurred concurrently across = 1 VOC, compounding health risks.^2,3 This prolonged 32-year VOC exposure window underlies current concerns regarding long-term cancer risk among affected service members, civilian employees, and family members. Epidemiologic research has found statistically significant associations between VOC exposure and multiple cancers, neurologic conditions, and reproductive issues.⁶ Specifically, TCE is associated with higher risks of hematologic cancers, multiple myeloma, NHL, and kidney cancer.³ PCE is linked with kidney cancer, benzene with multiple myeloma and NHL, and vinyl chloride with hepatobiliary cancers.³ A cohort mortality study compared Camp Lejeune personnel with a control group at Camp Pendleton from 1972 to 1985 and found a 3-fold higher incidence or mortality rate for kidney, esophageal, and female breast cancers, leukemia, and lymphoma among exposed Camp Lejeune personnel.⁶ Notably, personnel assigned to Camp Lejeune for as little as 6 months faced up to a 6-fold increase in cancer risk; the average military assignment between 1975 and 1985 was 18 months.^3,6

Honoring America's Veterans and Caring for Camp Lejeune Families Act of 2012, the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022, the Camp Lejeune Justice Act of 2022, and the pending Ensuring Justice for Camp Lejeune Victims Act of 2025 provide health care and legal resources for personnel and families affected by Camp Lejeune’s contaminated water.^6-8 These laws acknowledge associations between exposure and specific health conditions and expanded health care, benefits, and legal recourse for affected veterans, survivors, and their families.^8,9

CANCERS LINKED TO CAMP LEJEUNE

Camp Lejeune VOC-contaminated water exposure is associated with solid tumor and hematologic cancers. Symptoms, physical examination findings, and diagnostic considerations vary by cancer type (Table 1).

Bladder Cancer

The US incidence rate of bladder cancer for both males and females is 18 per 100,000 individuals per year, with a death rate of 4.1 per 100,000 individuals per year, and a 2.1% lifetime diagnosis risk.¹⁰ Personnel exposed to VOCs at Camp Lejeune had a 9% higher risk of developing bladder cancer and a 2% increased mortality compared with an unexposed control group at Camp Pendleton.^1,7 Other bladder cancer subtypes at increased risk are papillary transitional cell carcinoma, nonpapillary transition cell carcinoma, and urothelial carcinoma.⁷ This is consistent with prior research that found PCE exposure is associated with an increased risk for bladder cancer.^3,7,11 Smoking and tobacco use remain significant risk factors for bladder cancer.¹²

Symptomatology. The most common symptom associated with bladder cancer is painless hematuria (gross or microscopic). Other often delayed symptoms include urinary frequency, urgency, or nocturia.^13,14

Diagnostics. Screening tests include urinalysis for hematuria, urine cytology, and cystoscopy with biopsy as the gold standard for diagnosis and staging.^15,16

Kidney Cancer

The US incidence rate of kidney cancer and renal pelvis cancer for both males and females is 17.5 per 100,000 individuals per year, with a death rate of 3.4 per 100,000, and a 1.8% lifetime diagnosis risk.¹⁷ Camp Lejeune personnel exposed to VOCs had a 6% increased risk of developing kidney cancer and renal pelvis cancer and a 21% higher mortality risk compared with Camp Pendleton controls.^1,7 Subtypes at risk include renal cell carcinoma and papillary carcinoma.⁷ This is consistent with prior research that found exposures to TCE and PCE are associated with a 3-fold increased risk of kidney cancer.^3,7

Symptomatology. Hematuria, flank pain, and a palpable abdominal mass are common symptoms associated with kidney cancer. In advanced stages, other symptoms may include left-sided varicocele, anemia, weight loss, fatigue, fever, and night sweats.¹⁸

Diagnostics. Screening tests include urinalysis to assess the presence of blood, complete blood count (CBC) to assess anemia, calcium (elevated), and lactate dehydrogenase (LDH), which may be elevated. Imaging strategies include abdominal computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound.¹⁹

Esophageal Cancer

The US incidence rate of esophageal cancer for both males and females is 4.2 per 100,000 individuals per year, the death rate is 3.7 per 100,000 individuals per year, and a 0.5% lifetime diagnosis risk.²⁰ VOC-exposed Camp Lejeune personnel had a 27% increased incidence and 25% increased mortality compared with the control group.^1,7 Esophageal cancer subtypes at elevated risk include squamous cell carcinoma and adenocarcinoma. This is consistent with prior research that found Camp Lejeune water exposure is associated with a 3-fold increased risk for esophageal cancer.⁷ Additional risk factors include history of smoking and alcohol use.²¹

Symptomatology. Esophageal cancer is often asymptomatic with potential symptoms that include dysphagia, hoarseness, and weight loss in advanced disease.²²

Diagnostics. Endoscopy with biopsy is the definitive method for diagnosis.²³

Liver Cancer

The US incidence rate of liver cancer and intrahepatic bile duct cancer for both males and females is 9.4 per 100,000 individuals per year, with a death rate of 6.6 per 100,000 individuals per year, and a 1.1% lifetime diagnosis risk.²⁴ VOC-exposed personnel had a 1% higher mortality than controls.¹

Symptomatology. Liver cancer is often asymptomatic and appears in late stages.²⁵ Common symptoms include right upper quadrant pain, early satiety, nausea, vomiting, loss of appetite, weight loss, ascites, jaundice, and abnormal bleeding or bruising.^25,26

Diagnostics. Diagnostic tests may include an ultrasound, CT, or MRI. Additional laboratory testing may include liver function, a-fetoprotein blood, CBC, renal function, calcium, and hepatitis panel screening for hepatitis B and C.^27,28

Lung Cancer

The US incidence rate of lung cancer for both males and females is 47.8 per 100,000 individuals per year, with a death rate of 31.5 per 100,000 individuals per year, and a 5.4% lifetime diagnosis risk.²⁹ VOC-exposed personnel had a 16% increased risk and 19% higher mortality.^1,7 Subtypes include large cell, small cell, non-small cell, squamous cell, and adenocarcinoma.⁷ Smoking is an additional risk factor.³⁰

Symptomatology. Symptoms of lung cancer include cough, shortness of breath, chest pain worse with deep breathing, unexplained weight loss, fatigue, night sweats, and recurrent fevers. Advanced stages may metastasize or spread to the liver, bones, and brain.³¹

Diagnostics. Low-dose CT and chest X-ray are used for screening.³²

Breast Cancer

The US incidence rate of female breast cancer is 130.8 per 100,000 individuals per year, with a death rate of 19.2 per 100,000 individuals per year, and a 13.0% lifetime risk of diagnosis.³³ For female VOC-exposed personnel, there was an equal risk of developing breast cancer as the control group.¹ However, exposed females at Camp Lejeune had a 23% higher mortality risk compared to the control group.⁷ Breast cancer subtypes among females include ductal carcinoma, lobular carcinoma, and ductal-lobular carcinoma.¹

The US incidence rate of male breast cancer is 1.3 per 100,000 individuals per year, with a death rate of 0.3 per 100,000 individuals per year.^34,35 The lifetime risk for males developing breast cancer is 137.7 per 100,000 and about 70 to 100 times less common in men than women.³⁶

Male personnel exposed at Camp Lejeune had a 4% increased risk for developing breast cancer compared to Camp Pendleton.⁷ However, mortality was lower in the Camp Lejeune group.¹ Although male breast cancer is rare, males at Camp Lejeune had a higher incidence, indicating a link between TCE, PCE, vinyl chloride exposures and male breast cancer.³⁷ Male breast cancer is more often diagnosed in advanced stages than female breast cancer due to the lack of awareness or absence of routine screenings.³⁸ The most common breast cancer type in males is invasive ductal carcinoma, accounting for 85% to 90% of cases; lobular carcinoma is the second most common type.³⁹

Symptomatology. In both females and males, breast cancer symptoms include painless, firm mass or lump in the breast (left breast slightly more common than right), skin changes or dimpling, nipple retraction or turning inward, and nipple discharge. Breast cancer can spread to the lymph nodes and can be appreciated in axilla or clavicular regions.⁴⁰

Diagnostics. The diagnostic evaluation for breast cancer is similar for females and males. It includes a clinical breast examination, diagnostic mammogram, and ultrasound.⁴¹ Mammograms can distinguish between gynecomastia and cancer, especially in males.⁴² A core or fine needle biopsy is needed to confirm diagnosis.⁴¹

Adult Leukemia

The US incidence rate of leukemia for both male and female was 14.4 per 100,000 individuals per year, with a death rate of 5.8 per 100,000 individuals per year, and a 1.5% lifetime diagnosis risk.⁴³

VOC-exposed personnel had a 7% higher risk of developing leukemia and a 13% increased mortality risk compared with the control group.^1,7 Subtypes of leukemia at risk included a 38% increased incidence of acute myeloid/monocytic leukemia (AML) and a 2% increased incidence of chronic lymphocytic leukemia (CLL).¹ Benzene and TCE exposures are known risk factors for AML and other leukemias.⁷ Personnel at Camp Lejeune had 3 times the incidence or mortality for leukemia, specifically AML mortality at 20%.⁷ Smoking is an additional risk factor for certain leukemias, especially AML.³⁰

Symptomatology. Symptoms associated with leukemia are often nonspecific and may include fatigue, pallor, easy bruising or bleeding (skin or gums), recurrent infections secondary to neutropenia, fever, night sweats, pain or feeling full after a small meal due to enlarged spleen or liver, and weight loss.^44,45

Diagnostics. An initial screening includes a CBC with differential, a peripheral smear to detect the presence of blast cells, as well as Auer rods in myeloid blast cells in AML or smudge cells in CLL. Confirmatory tests may include bone marrow biopsy or flow cytometry. A referral to a hematologist is recommended for any suspected leukemia.^46,47

Myelodysplastic Syndromes

Aplastic anemia and MDS are considered rare disorders.⁴⁸ Aplastic anemia is a nonmalignant bone marrow failure disorder with pancytopenia and hypocellular bone marrow due to the loss of hematopoietic stem cells.⁴⁸ MDS is a type of hematopoietic cancer where the bone marrow produces abnormal blood cells or does not make enough healthy cells.⁴⁹ This can lead to an increased risk for infection, cytopenias, neutropenia, refractory anemia, and thrombocytopenia, and progression to AML in some patients.⁴⁹

The reported US incidence of MDS from 1975 to 2013 was 6.7 per 100,000 for males and 3.7 per 100,000 for females.⁵⁰ Benzene exposure is linked to MDS and a known cause of AML.¹ VOC-exposed personnel had a 68% increased risk of developing MDS and a 2.3-fold increased mortality risk compared to controls.^1,7

Symptomatology. Some patients are asymptomatic at diagnosis.⁵¹ Symptoms related to cytopenia include fatigue, pallor, purpura, petechiae, bleeding of skin, gum, or nose, recurrent infections, fever, bone pain, loss of appetite, and weight loss.^50,51

Diagnostics. Initial workup includes a CBC with differential to assess for anemia, white blood cell and absolute neutrophil counts (low), and thrombocytopenia.⁵² A peripheral blood smear may show myeloid blast cells. A bone marrow aspiration and biopsy, flow cytometry, and cytogenetic or molecular testing may be performed. If MDS is suspected, a referral to a hematologist should be considered.⁵²

Multiple Myeloma

The US incidence rate of multiple myeloma for both males and females is 7.3 per 100,000 individuals per year, with a mortality rate of 2.9 per 100,000 individuals per year, and a 0.8% lifetime diagnosis risk.⁵³ VOC-exposed personnel had a 13% increased risk of developing multiple myeloma and an 8% increased mortality risk compared to unexposed personnel.^1,7

Symptomatology. Multiple myeloma may be asymptomatic in early stages. The most common presenting symptom is bone pain, especially in the back, hips, and long bones, due to hypercalcemia from increased reabsorption, plasma cell tumor overgrowth in the bone marrow, and lytic lesions.⁵⁴ Additional symptoms include fatigue and pallor related to anemia, leukopenia, thrombocytopenia, recurrent infections, extreme thirst, frequent urination, dehydration, confusion associated with hypercalcemia, peripheral neuropathy, loss of appetite, weight loss, and renal impairment or failure.⁵⁴

Diagnostics. Testing considerations include a CBC with a peripheral blood smear to evaluate anemia and rouleaux formation of red blood cells (seen in > 50% of patients with multiple myeloma), comprehensive metabolic panel (CMP) to assess kidney function, calcium levels (elevated), serum and urine protein electrophoresis with immunofixation to detect monoclonal protein (detected in > 80% of patients with multiple myeloma) and Bence-Jones proteins, serum free light chain assay, and a bone marrow biopsy for diagnosis.^55,56

MRI of the spine and pelvis is the most sensitive to detecting bone marrow involvement and focal lesions before lytic lesion progression occurs and for assessing spinal cord compression.⁵⁷ PET/CT is more sensitive at detecting extramedullary disease, outside of the spine, and for patients that cannot undergo MRI.⁵⁷ A whole-body low-dose CT, either alone or with PET, is more sensitive than an X-ray at detecting lytic lesions, fractures, or osteoporosis associated with multiple myeloma.⁵⁷

Non-Hodgkin Lymphoma

The US incidence rate of NHL for both males and females are 18.7 per 100,000 individuals per year, the death rate is 4.9 per 100,000 individuals per year, and a 2% lifetime diagnosis risk.⁵⁸ VOC-exposed personnel had a 1% higher risk of developing NHL and a decreased mortality risk compared to the control group.^1,7 Specific NHL subtypes with increased risk in the exposed cohort are mantle cell (26%), follicular (7%), Burkitt (53%), and marginal zone B-cell (45%).⁷

Symptomatology. NHL often presents with painless lymphadenopathy or enlarged lymph nodes involving the cervical, axillary, inguinal regions.^59,60 Other symptoms include frequent infections, unexplained bruising, weight loss, and “B symptoms,” such as fever and night sweats.^59,60 Some patients develop a mediastinal mass in the thorax, which if large may lead to cough or shortness of breath.⁵⁹

Diagnostics. The initial diagnostic workup includes CBC with differential and LDH, which may be elevated.^60,61 Imaging may begin with a chest X-ray to assess for a mediastinal mass; however, CTs of the chest, abdomen, and pelvis provide more detail to better assess for NHL. Whole body PET/CT is considered the gold standard for assessing and staging systemic involvement. If enlarged lymph nodes are present, a biopsy can confirm the subtype of NHL.^60,61

PHYSICAL EXAMINATION

A focused physical examination may aid HCPs in early detection of the cancers associated with Camp Lejeune (Table 2). The physical examination can guide diagnostic testing and imaging for further assessment and workup for VOC-related cancers.

Proposed Diagnostic Screening Panel

Primary care and internal medicine HCPs have the opportunity to improve patient health outcomes by implementing a targeted diagnostic screening panel for identified veterans previously stationed at Camp Lejeune. Early identification of cancers associated with VOCs exposure can facilitate earlier treatment interventions and improve health and quality of life outcomes. The following diagnostic screening panel outlines a potential cost-effective strategy for evaluating and detecting the 10 cancers associated with VOC exposure in Camp Lejeune water.

Baseline Screening

Implementing a diagnostic screening panel in this high-risk cohort can lead to earlier diagnosis, reduce mortality, and improve patient outcomes through early intervention, which in turn may result in less invasive treatment. This approach may also reduce health care costs by avoiding costs associated with delayed diagnosis and advanced-stage cancer care (Tables 3 and 4).

A baseline panel of tests for exposed veterans could include:

• A CBC with differential and peripheral smear to assess for anemia, leukemia, thrombocytopenia, and blast cells associated with leukemias, MDS, multiple myeloma, and NHL.^{19,46,47,52,55,56,60,61}
• CMP evaluates calcium, total protein, renal and liver renal function. Elevated test results may indicate kidney or liver cancer or multiple myeloma.^{19,27,28,55,56}
• LDH testing may reveal levels that are elevated from tissue damage or high cell turnover in kidney cancer, multiple myeloma, and NHL.^{19,55,56,60,61}
• Urinalysis with microscopy may detect hematuria, proteinuria and cellular casts in bladder and kidney cancers.^13,24,19
• Low-dose CTs of the chest, abdomen, and pelvis are recommended for early identification of any masses or lymphadenopathy in lung, kidney, liver cancers, and NHL.^{19,27,28,32,60,61}

COST EFFICIENCY

Screening Panel Cost

According to the Medicare Clinical Laboratory Fee Schedule payment cap for 2018, the mean cost for the proposed blood workup was $35 (CBC, $10; CMP, $13; LDH, $8; urinalysis, $4).⁶² Medicare procedure price schedule for 2025 includes $351 for a CT of the abdomen and pelvis with and without contrast (Current Procedural Terminology [CPT] code 74177) and $187 for a CT of the chest with and without contrast (CPT code 71270).^63,64 The total proposed diagnostic screening panel payment cost about $572.

Cancer Care Cost

The average cost for initial cancer care across all cancer sites from 2007 to 2013 was $43,516 per patient; Camp Lejeune-associated cancers ranged from $26,443 for bladder cancer to $89,947 for esophageal cancer care.⁶⁴ Further, the last year of life cost across all cancer sites averaged $109,727, and Camp Lejeune-associated cancer types ranged from $76,101 for breast cancer to $169,588 for leukemia.⁶⁵

CONCLUSIONS

From 1953 to 1985, up to 1 million military personnel, civilian workers, and their families stationed at Camp Lejeune were unknowingly exposed to toxic and carcinogenic VOCs, which are associated with = 10 cancers, including bladder, kidney, esophageal, liver, lung, breast, and hematologic malignancies.^1-4 Some veterans may be asymptomatic, whereas others present with subtle or specific symptoms that can vary by individual and the type and stage of cancer. HCPs have an opportunity to improve patient outcomes through awareness in identifying symptoms associated with Camp Lejeune water exposure and performing a thorough baseline physical examination, especially noting lymphadenopathy, unexplained weight loss, or masses, which can guide further diagnostic evaluation. Timely screening can identify cancers earlier, reducing delays in care, mitigating the cost burden associated with advanced-stage cancer treatment, improving survival outcomes, and enhancing quality of life. Primary care and internal medicine HCPs specifically play a crucial role in early recognition, physical assessment, and appropriate screening tools. A proposed panel includes CBC with differential and peripheral smear, CMP, LDH, urinalysis, and low-dose CTs of the chest, abdomen and pelvis. Implementation should be guided by clinical judgment and patient-specific risk factors. The proposed diagnostic screening panel is a small price to pay for those who served in any capacity at Camp Lejeune.

Clinical awareness of cancers associated with Camp Lejeune water contamination exposure remains limited despite legal and policy advances. Gaps persist in early symptom recognition and timely diagnostic evaluation before a definitive cancer diagnosis among exposed personnel. This may represent missed opportunities for earlier identification of volatile organic compounds (VOCs)-related cancers and for less invasive treatment options for veterans in this high-risk population.

Federal health care practitioners (HCPs), especially those in primary care and internal medicine, are uniquely positioned to bridge this gap. By improving the recognition of symptoms, pertinent physical examination findings, and implementing a diagnostic screening panel, HCPs can support accurate diagnoses and facilitate earlier treatment to improve health and quality of life for this population.

From 1953 to 1985, as many as 1 million military personnel, civilian workers, and their families stationed at US Marine Corps Base Camp Lejeune were unknowingly exposed to toxic and carcinogenic chemicals in drinking and bathing water.¹ Three of the 8 main water sources on base were contaminated with VOCs, which are associated with multiple cancers.^1-3

The US Department of Veterans Affairs (VA) recognizes 15 conditions associated with Camp Lejeune contaminated water exposure for VA benefits, including 10 cancers: adult leukemia; aplastic anemia and other myelodysplastic syndromes (MDS); bladder, esophageal, kidney, liver, breast (male and female), and lung cancers; multiple myeloma; and non-Hodgkin lymphoma (NHL).⁴

BACKGROUND

Established in 1942, Camp Lejeune is an important Marine Corps training installation. Between 1953 and 1985, multiple on-base water systems were contaminated with VOCs, including trichloroethylene (TCE), perchloroethylene (PCE), benzene, and vinyl chloride, due to improper waste disposal and industrial runoff from on- and off-base sources.⁵ Tarawa Terrace water treatment plant (WTP) was contaminated primarily with PCE from November 1957 to February 1987. Hadnot Point WTP was contaminated with TCE from August 1953 to December 1984, along with PCE, and benzene, toluene, ethylbenzene, and xylene (BTEX). Holcomb Boulevard WTP, established in 1972, was contaminated with TCE from June 1972 to February 1985.² These contaminants entered the drinking and bathing water supply over decades, and exposure often occurred concurrently across = 1 VOC, compounding health risks.^2,3 This prolonged 32-year VOC exposure window underlies current concerns regarding long-term cancer risk among affected service members, civilian employees, and family members. Epidemiologic research has found statistically significant associations between VOC exposure and multiple cancers, neurologic conditions, and reproductive issues.⁶ Specifically, TCE is associated with higher risks of hematologic cancers, multiple myeloma, NHL, and kidney cancer.³ PCE is linked with kidney cancer, benzene with multiple myeloma and NHL, and vinyl chloride with hepatobiliary cancers.³ A cohort mortality study compared Camp Lejeune personnel with a control group at Camp Pendleton from 1972 to 1985 and found a 3-fold higher incidence or mortality rate for kidney, esophageal, and female breast cancers, leukemia, and lymphoma among exposed Camp Lejeune personnel.⁶ Notably, personnel assigned to Camp Lejeune for as little as 6 months faced up to a 6-fold increase in cancer risk; the average military assignment between 1975 and 1985 was 18 months.^3,6

Honoring America's Veterans and Caring for Camp Lejeune Families Act of 2012, the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022, the Camp Lejeune Justice Act of 2022, and the pending Ensuring Justice for Camp Lejeune Victims Act of 2025 provide health care and legal resources for personnel and families affected by Camp Lejeune’s contaminated water.^6-8 These laws acknowledge associations between exposure and specific health conditions and expanded health care, benefits, and legal recourse for affected veterans, survivors, and their families.^8,9

CANCERS LINKED TO CAMP LEJEUNE

Camp Lejeune VOC-contaminated water exposure is associated with solid tumor and hematologic cancers. Symptoms, physical examination findings, and diagnostic considerations vary by cancer type (Table 1).

Bladder Cancer

The US incidence rate of bladder cancer for both males and females is 18 per 100,000 individuals per year, with a death rate of 4.1 per 100,000 individuals per year, and a 2.1% lifetime diagnosis risk.¹⁰ Personnel exposed to VOCs at Camp Lejeune had a 9% higher risk of developing bladder cancer and a 2% increased mortality compared with an unexposed control group at Camp Pendleton.^1,7 Other bladder cancer subtypes at increased risk are papillary transitional cell carcinoma, nonpapillary transition cell carcinoma, and urothelial carcinoma.⁷ This is consistent with prior research that found PCE exposure is associated with an increased risk for bladder cancer.^3,7,11 Smoking and tobacco use remain significant risk factors for bladder cancer.¹²

Symptomatology. The most common symptom associated with bladder cancer is painless hematuria (gross or microscopic). Other often delayed symptoms include urinary frequency, urgency, or nocturia.^13,14

Diagnostics. Screening tests include urinalysis for hematuria, urine cytology, and cystoscopy with biopsy as the gold standard for diagnosis and staging.^15,16

Kidney Cancer

The US incidence rate of kidney cancer and renal pelvis cancer for both males and females is 17.5 per 100,000 individuals per year, with a death rate of 3.4 per 100,000, and a 1.8% lifetime diagnosis risk.¹⁷ Camp Lejeune personnel exposed to VOCs had a 6% increased risk of developing kidney cancer and renal pelvis cancer and a 21% higher mortality risk compared with Camp Pendleton controls.^1,7 Subtypes at risk include renal cell carcinoma and papillary carcinoma.⁷ This is consistent with prior research that found exposures to TCE and PCE are associated with a 3-fold increased risk of kidney cancer.^3,7

Symptomatology. Hematuria, flank pain, and a palpable abdominal mass are common symptoms associated with kidney cancer. In advanced stages, other symptoms may include left-sided varicocele, anemia, weight loss, fatigue, fever, and night sweats.¹⁸

Diagnostics. Screening tests include urinalysis to assess the presence of blood, complete blood count (CBC) to assess anemia, calcium (elevated), and lactate dehydrogenase (LDH), which may be elevated. Imaging strategies include abdominal computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound.¹⁹

Esophageal Cancer

The US incidence rate of esophageal cancer for both males and females is 4.2 per 100,000 individuals per year, the death rate is 3.7 per 100,000 individuals per year, and a 0.5% lifetime diagnosis risk.²⁰ VOC-exposed Camp Lejeune personnel had a 27% increased incidence and 25% increased mortality compared with the control group.^1,7 Esophageal cancer subtypes at elevated risk include squamous cell carcinoma and adenocarcinoma. This is consistent with prior research that found Camp Lejeune water exposure is associated with a 3-fold increased risk for esophageal cancer.⁷ Additional risk factors include history of smoking and alcohol use.²¹

Symptomatology. Esophageal cancer is often asymptomatic with potential symptoms that include dysphagia, hoarseness, and weight loss in advanced disease.²²

Diagnostics. Endoscopy with biopsy is the definitive method for diagnosis.²³

Liver Cancer

The US incidence rate of liver cancer and intrahepatic bile duct cancer for both males and females is 9.4 per 100,000 individuals per year, with a death rate of 6.6 per 100,000 individuals per year, and a 1.1% lifetime diagnosis risk.²⁴ VOC-exposed personnel had a 1% higher mortality than controls.¹

Symptomatology. Liver cancer is often asymptomatic and appears in late stages.²⁵ Common symptoms include right upper quadrant pain, early satiety, nausea, vomiting, loss of appetite, weight loss, ascites, jaundice, and abnormal bleeding or bruising.^25,26

Diagnostics. Diagnostic tests may include an ultrasound, CT, or MRI. Additional laboratory testing may include liver function, a-fetoprotein blood, CBC, renal function, calcium, and hepatitis panel screening for hepatitis B and C.^27,28

Lung Cancer

The US incidence rate of lung cancer for both males and females is 47.8 per 100,000 individuals per year, with a death rate of 31.5 per 100,000 individuals per year, and a 5.4% lifetime diagnosis risk.²⁹ VOC-exposed personnel had a 16% increased risk and 19% higher mortality.^1,7 Subtypes include large cell, small cell, non-small cell, squamous cell, and adenocarcinoma.⁷ Smoking is an additional risk factor.³⁰

Symptomatology. Symptoms of lung cancer include cough, shortness of breath, chest pain worse with deep breathing, unexplained weight loss, fatigue, night sweats, and recurrent fevers. Advanced stages may metastasize or spread to the liver, bones, and brain.³¹

Diagnostics. Low-dose CT and chest X-ray are used for screening.³²

Breast Cancer

The US incidence rate of female breast cancer is 130.8 per 100,000 individuals per year, with a death rate of 19.2 per 100,000 individuals per year, and a 13.0% lifetime risk of diagnosis.³³ For female VOC-exposed personnel, there was an equal risk of developing breast cancer as the control group.¹ However, exposed females at Camp Lejeune had a 23% higher mortality risk compared to the control group.⁷ Breast cancer subtypes among females include ductal carcinoma, lobular carcinoma, and ductal-lobular carcinoma.¹

The US incidence rate of male breast cancer is 1.3 per 100,000 individuals per year, with a death rate of 0.3 per 100,000 individuals per year.^34,35 The lifetime risk for males developing breast cancer is 137.7 per 100,000 and about 70 to 100 times less common in men than women.³⁶

Male personnel exposed at Camp Lejeune had a 4% increased risk for developing breast cancer compared to Camp Pendleton.⁷ However, mortality was lower in the Camp Lejeune group.¹ Although male breast cancer is rare, males at Camp Lejeune had a higher incidence, indicating a link between TCE, PCE, vinyl chloride exposures and male breast cancer.³⁷ Male breast cancer is more often diagnosed in advanced stages than female breast cancer due to the lack of awareness or absence of routine screenings.³⁸ The most common breast cancer type in males is invasive ductal carcinoma, accounting for 85% to 90% of cases; lobular carcinoma is the second most common type.³⁹

Symptomatology. In both females and males, breast cancer symptoms include painless, firm mass or lump in the breast (left breast slightly more common than right), skin changes or dimpling, nipple retraction or turning inward, and nipple discharge. Breast cancer can spread to the lymph nodes and can be appreciated in axilla or clavicular regions.⁴⁰

Diagnostics. The diagnostic evaluation for breast cancer is similar for females and males. It includes a clinical breast examination, diagnostic mammogram, and ultrasound.⁴¹ Mammograms can distinguish between gynecomastia and cancer, especially in males.⁴² A core or fine needle biopsy is needed to confirm diagnosis.⁴¹

Adult Leukemia

The US incidence rate of leukemia for both male and female was 14.4 per 100,000 individuals per year, with a death rate of 5.8 per 100,000 individuals per year, and a 1.5% lifetime diagnosis risk.⁴³

VOC-exposed personnel had a 7% higher risk of developing leukemia and a 13% increased mortality risk compared with the control group.^1,7 Subtypes of leukemia at risk included a 38% increased incidence of acute myeloid/monocytic leukemia (AML) and a 2% increased incidence of chronic lymphocytic leukemia (CLL).¹ Benzene and TCE exposures are known risk factors for AML and other leukemias.⁷ Personnel at Camp Lejeune had 3 times the incidence or mortality for leukemia, specifically AML mortality at 20%.⁷ Smoking is an additional risk factor for certain leukemias, especially AML.³⁰

Symptomatology. Symptoms associated with leukemia are often nonspecific and may include fatigue, pallor, easy bruising or bleeding (skin or gums), recurrent infections secondary to neutropenia, fever, night sweats, pain or feeling full after a small meal due to enlarged spleen or liver, and weight loss.^44,45

Diagnostics. An initial screening includes a CBC with differential, a peripheral smear to detect the presence of blast cells, as well as Auer rods in myeloid blast cells in AML or smudge cells in CLL. Confirmatory tests may include bone marrow biopsy or flow cytometry. A referral to a hematologist is recommended for any suspected leukemia.^46,47

Myelodysplastic Syndromes

Aplastic anemia and MDS are considered rare disorders.⁴⁸ Aplastic anemia is a nonmalignant bone marrow failure disorder with pancytopenia and hypocellular bone marrow due to the loss of hematopoietic stem cells.⁴⁸ MDS is a type of hematopoietic cancer where the bone marrow produces abnormal blood cells or does not make enough healthy cells.⁴⁹ This can lead to an increased risk for infection, cytopenias, neutropenia, refractory anemia, and thrombocytopenia, and progression to AML in some patients.⁴⁹

The reported US incidence of MDS from 1975 to 2013 was 6.7 per 100,000 for males and 3.7 per 100,000 for females.⁵⁰ Benzene exposure is linked to MDS and a known cause of AML.¹ VOC-exposed personnel had a 68% increased risk of developing MDS and a 2.3-fold increased mortality risk compared to controls.^1,7

Symptomatology. Some patients are asymptomatic at diagnosis.⁵¹ Symptoms related to cytopenia include fatigue, pallor, purpura, petechiae, bleeding of skin, gum, or nose, recurrent infections, fever, bone pain, loss of appetite, and weight loss.^50,51

Diagnostics. Initial workup includes a CBC with differential to assess for anemia, white blood cell and absolute neutrophil counts (low), and thrombocytopenia.⁵² A peripheral blood smear may show myeloid blast cells. A bone marrow aspiration and biopsy, flow cytometry, and cytogenetic or molecular testing may be performed. If MDS is suspected, a referral to a hematologist should be considered.⁵²

Multiple Myeloma

The US incidence rate of multiple myeloma for both males and females is 7.3 per 100,000 individuals per year, with a mortality rate of 2.9 per 100,000 individuals per year, and a 0.8% lifetime diagnosis risk.⁵³ VOC-exposed personnel had a 13% increased risk of developing multiple myeloma and an 8% increased mortality risk compared to unexposed personnel.^1,7

Symptomatology. Multiple myeloma may be asymptomatic in early stages. The most common presenting symptom is bone pain, especially in the back, hips, and long bones, due to hypercalcemia from increased reabsorption, plasma cell tumor overgrowth in the bone marrow, and lytic lesions.⁵⁴ Additional symptoms include fatigue and pallor related to anemia, leukopenia, thrombocytopenia, recurrent infections, extreme thirst, frequent urination, dehydration, confusion associated with hypercalcemia, peripheral neuropathy, loss of appetite, weight loss, and renal impairment or failure.⁵⁴

Diagnostics. Testing considerations include a CBC with a peripheral blood smear to evaluate anemia and rouleaux formation of red blood cells (seen in > 50% of patients with multiple myeloma), comprehensive metabolic panel (CMP) to assess kidney function, calcium levels (elevated), serum and urine protein electrophoresis with immunofixation to detect monoclonal protein (detected in > 80% of patients with multiple myeloma) and Bence-Jones proteins, serum free light chain assay, and a bone marrow biopsy for diagnosis.^55,56

MRI of the spine and pelvis is the most sensitive to detecting bone marrow involvement and focal lesions before lytic lesion progression occurs and for assessing spinal cord compression.⁵⁷ PET/CT is more sensitive at detecting extramedullary disease, outside of the spine, and for patients that cannot undergo MRI.⁵⁷ A whole-body low-dose CT, either alone or with PET, is more sensitive than an X-ray at detecting lytic lesions, fractures, or osteoporosis associated with multiple myeloma.⁵⁷

Non-Hodgkin Lymphoma

The US incidence rate of NHL for both males and females are 18.7 per 100,000 individuals per year, the death rate is 4.9 per 100,000 individuals per year, and a 2% lifetime diagnosis risk.⁵⁸ VOC-exposed personnel had a 1% higher risk of developing NHL and a decreased mortality risk compared to the control group.^1,7 Specific NHL subtypes with increased risk in the exposed cohort are mantle cell (26%), follicular (7%), Burkitt (53%), and marginal zone B-cell (45%).⁷

Symptomatology. NHL often presents with painless lymphadenopathy or enlarged lymph nodes involving the cervical, axillary, inguinal regions.^59,60 Other symptoms include frequent infections, unexplained bruising, weight loss, and “B symptoms,” such as fever and night sweats.^59,60 Some patients develop a mediastinal mass in the thorax, which if large may lead to cough or shortness of breath.⁵⁹

Diagnostics. The initial diagnostic workup includes CBC with differential and LDH, which may be elevated.^60,61 Imaging may begin with a chest X-ray to assess for a mediastinal mass; however, CTs of the chest, abdomen, and pelvis provide more detail to better assess for NHL. Whole body PET/CT is considered the gold standard for assessing and staging systemic involvement. If enlarged lymph nodes are present, a biopsy can confirm the subtype of NHL.^60,61

PHYSICAL EXAMINATION

A focused physical examination may aid HCPs in early detection of the cancers associated with Camp Lejeune (Table 2). The physical examination can guide diagnostic testing and imaging for further assessment and workup for VOC-related cancers.

Proposed Diagnostic Screening Panel

Primary care and internal medicine HCPs have the opportunity to improve patient health outcomes by implementing a targeted diagnostic screening panel for identified veterans previously stationed at Camp Lejeune. Early identification of cancers associated with VOCs exposure can facilitate earlier treatment interventions and improve health and quality of life outcomes. The following diagnostic screening panel outlines a potential cost-effective strategy for evaluating and detecting the 10 cancers associated with VOC exposure in Camp Lejeune water.

Baseline Screening

Implementing a diagnostic screening panel in this high-risk cohort can lead to earlier diagnosis, reduce mortality, and improve patient outcomes through early intervention, which in turn may result in less invasive treatment. This approach may also reduce health care costs by avoiding costs associated with delayed diagnosis and advanced-stage cancer care (Tables 3 and 4).

A baseline panel of tests for exposed veterans could include:

• A CBC with differential and peripheral smear to assess for anemia, leukemia, thrombocytopenia, and blast cells associated with leukemias, MDS, multiple myeloma, and NHL.^{19,46,47,52,55,56,60,61}
• CMP evaluates calcium, total protein, renal and liver renal function. Elevated test results may indicate kidney or liver cancer or multiple myeloma.^{19,27,28,55,56}
• LDH testing may reveal levels that are elevated from tissue damage or high cell turnover in kidney cancer, multiple myeloma, and NHL.^{19,55,56,60,61}
• Urinalysis with microscopy may detect hematuria, proteinuria and cellular casts in bladder and kidney cancers.^13,24,19
• Low-dose CTs of the chest, abdomen, and pelvis are recommended for early identification of any masses or lymphadenopathy in lung, kidney, liver cancers, and NHL.^{19,27,28,32,60,61}

COST EFFICIENCY

Screening Panel Cost

According to the Medicare Clinical Laboratory Fee Schedule payment cap for 2018, the mean cost for the proposed blood workup was $35 (CBC, $10; CMP, $13; LDH, $8; urinalysis, $4).⁶² Medicare procedure price schedule for 2025 includes $351 for a CT of the abdomen and pelvis with and without contrast (Current Procedural Terminology [CPT] code 74177) and $187 for a CT of the chest with and without contrast (CPT code 71270).^63,64 The total proposed diagnostic screening panel payment cost about $572.

Cancer Care Cost

The average cost for initial cancer care across all cancer sites from 2007 to 2013 was $43,516 per patient; Camp Lejeune-associated cancers ranged from $26,443 for bladder cancer to $89,947 for esophageal cancer care.⁶⁴ Further, the last year of life cost across all cancer sites averaged $109,727, and Camp Lejeune-associated cancer types ranged from $76,101 for breast cancer to $169,588 for leukemia.⁶⁵

CONCLUSIONS

From 1953 to 1985, up to 1 million military personnel, civilian workers, and their families stationed at Camp Lejeune were unknowingly exposed to toxic and carcinogenic VOCs, which are associated with = 10 cancers, including bladder, kidney, esophageal, liver, lung, breast, and hematologic malignancies.^1-4 Some veterans may be asymptomatic, whereas others present with subtle or specific symptoms that can vary by individual and the type and stage of cancer. HCPs have an opportunity to improve patient outcomes through awareness in identifying symptoms associated with Camp Lejeune water exposure and performing a thorough baseline physical examination, especially noting lymphadenopathy, unexplained weight loss, or masses, which can guide further diagnostic evaluation. Timely screening can identify cancers earlier, reducing delays in care, mitigating the cost burden associated with advanced-stage cancer treatment, improving survival outcomes, and enhancing quality of life. Primary care and internal medicine HCPs specifically play a crucial role in early recognition, physical assessment, and appropriate screening tools. A proposed panel includes CBC with differential and peripheral smear, CMP, LDH, urinalysis, and low-dose CTs of the chest, abdomen and pelvis. Implementation should be guided by clinical judgment and patient-specific risk factors. The proposed diagnostic screening panel is a small price to pay for those who served in any capacity at Camp Lejeune.

Clinical awareness of cancers associated with Camp Lejeune water contamination exposure remains limited despite legal and policy advances. Gaps persist in early symptom recognition and timely diagnostic evaluation before a definitive cancer diagnosis among exposed personnel. This may represent missed opportunities for earlier identification of volatile organic compounds (VOCs)-related cancers and for less invasive treatment options for veterans in this high-risk population.

Federal health care practitioners (HCPs), especially those in primary care and internal medicine, are uniquely positioned to bridge this gap. By improving the recognition of symptoms, pertinent physical examination findings, and implementing a diagnostic screening panel, HCPs can support accurate diagnoses and facilitate earlier treatment to improve health and quality of life for this population.

From 1953 to 1985, as many as 1 million military personnel, civilian workers, and their families stationed at US Marine Corps Base Camp Lejeune were unknowingly exposed to toxic and carcinogenic chemicals in drinking and bathing water.¹ Three of the 8 main water sources on base were contaminated with VOCs, which are associated with multiple cancers.^1-3

The US Department of Veterans Affairs (VA) recognizes 15 conditions associated with Camp Lejeune contaminated water exposure for VA benefits, including 10 cancers: adult leukemia; aplastic anemia and other myelodysplastic syndromes (MDS); bladder, esophageal, kidney, liver, breast (male and female), and lung cancers; multiple myeloma; and non-Hodgkin lymphoma (NHL).⁴

BACKGROUND

Established in 1942, Camp Lejeune is an important Marine Corps training installation. Between 1953 and 1985, multiple on-base water systems were contaminated with VOCs, including trichloroethylene (TCE), perchloroethylene (PCE), benzene, and vinyl chloride, due to improper waste disposal and industrial runoff from on- and off-base sources.⁵ Tarawa Terrace water treatment plant (WTP) was contaminated primarily with PCE from November 1957 to February 1987. Hadnot Point WTP was contaminated with TCE from August 1953 to December 1984, along with PCE, and benzene, toluene, ethylbenzene, and xylene (BTEX). Holcomb Boulevard WTP, established in 1972, was contaminated with TCE from June 1972 to February 1985.² These contaminants entered the drinking and bathing water supply over decades, and exposure often occurred concurrently across = 1 VOC, compounding health risks.^2,3 This prolonged 32-year VOC exposure window underlies current concerns regarding long-term cancer risk among affected service members, civilian employees, and family members. Epidemiologic research has found statistically significant associations between VOC exposure and multiple cancers, neurologic conditions, and reproductive issues.⁶ Specifically, TCE is associated with higher risks of hematologic cancers, multiple myeloma, NHL, and kidney cancer.³ PCE is linked with kidney cancer, benzene with multiple myeloma and NHL, and vinyl chloride with hepatobiliary cancers.³ A cohort mortality study compared Camp Lejeune personnel with a control group at Camp Pendleton from 1972 to 1985 and found a 3-fold higher incidence or mortality rate for kidney, esophageal, and female breast cancers, leukemia, and lymphoma among exposed Camp Lejeune personnel.⁶ Notably, personnel assigned to Camp Lejeune for as little as 6 months faced up to a 6-fold increase in cancer risk; the average military assignment between 1975 and 1985 was 18 months.^3,6

Honoring America's Veterans and Caring for Camp Lejeune Families Act of 2012, the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022, the Camp Lejeune Justice Act of 2022, and the pending Ensuring Justice for Camp Lejeune Victims Act of 2025 provide health care and legal resources for personnel and families affected by Camp Lejeune’s contaminated water.^6-8 These laws acknowledge associations between exposure and specific health conditions and expanded health care, benefits, and legal recourse for affected veterans, survivors, and their families.^8,9

CANCERS LINKED TO CAMP LEJEUNE

Camp Lejeune VOC-contaminated water exposure is associated with solid tumor and hematologic cancers. Symptoms, physical examination findings, and diagnostic considerations vary by cancer type (Table 1).

Bladder Cancer

The US incidence rate of bladder cancer for both males and females is 18 per 100,000 individuals per year, with a death rate of 4.1 per 100,000 individuals per year, and a 2.1% lifetime diagnosis risk.¹⁰ Personnel exposed to VOCs at Camp Lejeune had a 9% higher risk of developing bladder cancer and a 2% increased mortality compared with an unexposed control group at Camp Pendleton.^1,7 Other bladder cancer subtypes at increased risk are papillary transitional cell carcinoma, nonpapillary transition cell carcinoma, and urothelial carcinoma.⁷ This is consistent with prior research that found PCE exposure is associated with an increased risk for bladder cancer.^3,7,11 Smoking and tobacco use remain significant risk factors for bladder cancer.¹²

Symptomatology. The most common symptom associated with bladder cancer is painless hematuria (gross or microscopic). Other often delayed symptoms include urinary frequency, urgency, or nocturia.^13,14

Diagnostics. Screening tests include urinalysis for hematuria, urine cytology, and cystoscopy with biopsy as the gold standard for diagnosis and staging.^15,16

Kidney Cancer

The US incidence rate of kidney cancer and renal pelvis cancer for both males and females is 17.5 per 100,000 individuals per year, with a death rate of 3.4 per 100,000, and a 1.8% lifetime diagnosis risk.¹⁷ Camp Lejeune personnel exposed to VOCs had a 6% increased risk of developing kidney cancer and renal pelvis cancer and a 21% higher mortality risk compared with Camp Pendleton controls.^1,7 Subtypes at risk include renal cell carcinoma and papillary carcinoma.⁷ This is consistent with prior research that found exposures to TCE and PCE are associated with a 3-fold increased risk of kidney cancer.^3,7

Symptomatology. Hematuria, flank pain, and a palpable abdominal mass are common symptoms associated with kidney cancer. In advanced stages, other symptoms may include left-sided varicocele, anemia, weight loss, fatigue, fever, and night sweats.¹⁸

Diagnostics. Screening tests include urinalysis to assess the presence of blood, complete blood count (CBC) to assess anemia, calcium (elevated), and lactate dehydrogenase (LDH), which may be elevated. Imaging strategies include abdominal computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound.¹⁹

Esophageal Cancer

The US incidence rate of esophageal cancer for both males and females is 4.2 per 100,000 individuals per year, the death rate is 3.7 per 100,000 individuals per year, and a 0.5% lifetime diagnosis risk.²⁰ VOC-exposed Camp Lejeune personnel had a 27% increased incidence and 25% increased mortality compared with the control group.^1,7 Esophageal cancer subtypes at elevated risk include squamous cell carcinoma and adenocarcinoma. This is consistent with prior research that found Camp Lejeune water exposure is associated with a 3-fold increased risk for esophageal cancer.⁷ Additional risk factors include history of smoking and alcohol use.²¹

Symptomatology. Esophageal cancer is often asymptomatic with potential symptoms that include dysphagia, hoarseness, and weight loss in advanced disease.²²

Diagnostics. Endoscopy with biopsy is the definitive method for diagnosis.²³

Liver Cancer

The US incidence rate of liver cancer and intrahepatic bile duct cancer for both males and females is 9.4 per 100,000 individuals per year, with a death rate of 6.6 per 100,000 individuals per year, and a 1.1% lifetime diagnosis risk.²⁴ VOC-exposed personnel had a 1% higher mortality than controls.¹

Symptomatology. Liver cancer is often asymptomatic and appears in late stages.²⁵ Common symptoms include right upper quadrant pain, early satiety, nausea, vomiting, loss of appetite, weight loss, ascites, jaundice, and abnormal bleeding or bruising.^25,26

Diagnostics. Diagnostic tests may include an ultrasound, CT, or MRI. Additional laboratory testing may include liver function, a-fetoprotein blood, CBC, renal function, calcium, and hepatitis panel screening for hepatitis B and C.^27,28

Lung Cancer

The US incidence rate of lung cancer for both males and females is 47.8 per 100,000 individuals per year, with a death rate of 31.5 per 100,000 individuals per year, and a 5.4% lifetime diagnosis risk.²⁹ VOC-exposed personnel had a 16% increased risk and 19% higher mortality.^1,7 Subtypes include large cell, small cell, non-small cell, squamous cell, and adenocarcinoma.⁷ Smoking is an additional risk factor.³⁰

Symptomatology. Symptoms of lung cancer include cough, shortness of breath, chest pain worse with deep breathing, unexplained weight loss, fatigue, night sweats, and recurrent fevers. Advanced stages may metastasize or spread to the liver, bones, and brain.³¹

Diagnostics. Low-dose CT and chest X-ray are used for screening.³²

Breast Cancer

The US incidence rate of female breast cancer is 130.8 per 100,000 individuals per year, with a death rate of 19.2 per 100,000 individuals per year, and a 13.0% lifetime risk of diagnosis.³³ For female VOC-exposed personnel, there was an equal risk of developing breast cancer as the control group.¹ However, exposed females at Camp Lejeune had a 23% higher mortality risk compared to the control group.⁷ Breast cancer subtypes among females include ductal carcinoma, lobular carcinoma, and ductal-lobular carcinoma.¹

The US incidence rate of male breast cancer is 1.3 per 100,000 individuals per year, with a death rate of 0.3 per 100,000 individuals per year.^34,35 The lifetime risk for males developing breast cancer is 137.7 per 100,000 and about 70 to 100 times less common in men than women.³⁶

Male personnel exposed at Camp Lejeune had a 4% increased risk for developing breast cancer compared to Camp Pendleton.⁷ However, mortality was lower in the Camp Lejeune group.¹ Although male breast cancer is rare, males at Camp Lejeune had a higher incidence, indicating a link between TCE, PCE, vinyl chloride exposures and male breast cancer.³⁷ Male breast cancer is more often diagnosed in advanced stages than female breast cancer due to the lack of awareness or absence of routine screenings.³⁸ The most common breast cancer type in males is invasive ductal carcinoma, accounting for 85% to 90% of cases; lobular carcinoma is the second most common type.³⁹

Symptomatology. In both females and males, breast cancer symptoms include painless, firm mass or lump in the breast (left breast slightly more common than right), skin changes or dimpling, nipple retraction or turning inward, and nipple discharge. Breast cancer can spread to the lymph nodes and can be appreciated in axilla or clavicular regions.⁴⁰

Diagnostics. The diagnostic evaluation for breast cancer is similar for females and males. It includes a clinical breast examination, diagnostic mammogram, and ultrasound.⁴¹ Mammograms can distinguish between gynecomastia and cancer, especially in males.⁴² A core or fine needle biopsy is needed to confirm diagnosis.⁴¹

Adult Leukemia

The US incidence rate of leukemia for both male and female was 14.4 per 100,000 individuals per year, with a death rate of 5.8 per 100,000 individuals per year, and a 1.5% lifetime diagnosis risk.⁴³

VOC-exposed personnel had a 7% higher risk of developing leukemia and a 13% increased mortality risk compared with the control group.^1,7 Subtypes of leukemia at risk included a 38% increased incidence of acute myeloid/monocytic leukemia (AML) and a 2% increased incidence of chronic lymphocytic leukemia (CLL).¹ Benzene and TCE exposures are known risk factors for AML and other leukemias.⁷ Personnel at Camp Lejeune had 3 times the incidence or mortality for leukemia, specifically AML mortality at 20%.⁷ Smoking is an additional risk factor for certain leukemias, especially AML.³⁰

Symptomatology. Symptoms associated with leukemia are often nonspecific and may include fatigue, pallor, easy bruising or bleeding (skin or gums), recurrent infections secondary to neutropenia, fever, night sweats, pain or feeling full after a small meal due to enlarged spleen or liver, and weight loss.^44,45

Diagnostics. An initial screening includes a CBC with differential, a peripheral smear to detect the presence of blast cells, as well as Auer rods in myeloid blast cells in AML or smudge cells in CLL. Confirmatory tests may include bone marrow biopsy or flow cytometry. A referral to a hematologist is recommended for any suspected leukemia.^46,47

Myelodysplastic Syndromes

Aplastic anemia and MDS are considered rare disorders.⁴⁸ Aplastic anemia is a nonmalignant bone marrow failure disorder with pancytopenia and hypocellular bone marrow due to the loss of hematopoietic stem cells.⁴⁸ MDS is a type of hematopoietic cancer where the bone marrow produces abnormal blood cells or does not make enough healthy cells.⁴⁹ This can lead to an increased risk for infection, cytopenias, neutropenia, refractory anemia, and thrombocytopenia, and progression to AML in some patients.⁴⁹

The reported US incidence of MDS from 1975 to 2013 was 6.7 per 100,000 for males and 3.7 per 100,000 for females.⁵⁰ Benzene exposure is linked to MDS and a known cause of AML.¹ VOC-exposed personnel had a 68% increased risk of developing MDS and a 2.3-fold increased mortality risk compared to controls.^1,7

Symptomatology. Some patients are asymptomatic at diagnosis.⁵¹ Symptoms related to cytopenia include fatigue, pallor, purpura, petechiae, bleeding of skin, gum, or nose, recurrent infections, fever, bone pain, loss of appetite, and weight loss.^50,51

Diagnostics. Initial workup includes a CBC with differential to assess for anemia, white blood cell and absolute neutrophil counts (low), and thrombocytopenia.⁵² A peripheral blood smear may show myeloid blast cells. A bone marrow aspiration and biopsy, flow cytometry, and cytogenetic or molecular testing may be performed. If MDS is suspected, a referral to a hematologist should be considered.⁵²

Multiple Myeloma

The US incidence rate of multiple myeloma for both males and females is 7.3 per 100,000 individuals per year, with a mortality rate of 2.9 per 100,000 individuals per year, and a 0.8% lifetime diagnosis risk.⁵³ VOC-exposed personnel had a 13% increased risk of developing multiple myeloma and an 8% increased mortality risk compared to unexposed personnel.^1,7

Symptomatology. Multiple myeloma may be asymptomatic in early stages. The most common presenting symptom is bone pain, especially in the back, hips, and long bones, due to hypercalcemia from increased reabsorption, plasma cell tumor overgrowth in the bone marrow, and lytic lesions.⁵⁴ Additional symptoms include fatigue and pallor related to anemia, leukopenia, thrombocytopenia, recurrent infections, extreme thirst, frequent urination, dehydration, confusion associated with hypercalcemia, peripheral neuropathy, loss of appetite, weight loss, and renal impairment or failure.⁵⁴

Diagnostics. Testing considerations include a CBC with a peripheral blood smear to evaluate anemia and rouleaux formation of red blood cells (seen in > 50% of patients with multiple myeloma), comprehensive metabolic panel (CMP) to assess kidney function, calcium levels (elevated), serum and urine protein electrophoresis with immunofixation to detect monoclonal protein (detected in > 80% of patients with multiple myeloma) and Bence-Jones proteins, serum free light chain assay, and a bone marrow biopsy for diagnosis.^55,56

MRI of the spine and pelvis is the most sensitive to detecting bone marrow involvement and focal lesions before lytic lesion progression occurs and for assessing spinal cord compression.⁵⁷ PET/CT is more sensitive at detecting extramedullary disease, outside of the spine, and for patients that cannot undergo MRI.⁵⁷ A whole-body low-dose CT, either alone or with PET, is more sensitive than an X-ray at detecting lytic lesions, fractures, or osteoporosis associated with multiple myeloma.⁵⁷

Non-Hodgkin Lymphoma

The US incidence rate of NHL for both males and females are 18.7 per 100,000 individuals per year, the death rate is 4.9 per 100,000 individuals per year, and a 2% lifetime diagnosis risk.⁵⁸ VOC-exposed personnel had a 1% higher risk of developing NHL and a decreased mortality risk compared to the control group.^1,7 Specific NHL subtypes with increased risk in the exposed cohort are mantle cell (26%), follicular (7%), Burkitt (53%), and marginal zone B-cell (45%).⁷

Symptomatology. NHL often presents with painless lymphadenopathy or enlarged lymph nodes involving the cervical, axillary, inguinal regions.^59,60 Other symptoms include frequent infections, unexplained bruising, weight loss, and “B symptoms,” such as fever and night sweats.^59,60 Some patients develop a mediastinal mass in the thorax, which if large may lead to cough or shortness of breath.⁵⁹

Diagnostics. The initial diagnostic workup includes CBC with differential and LDH, which may be elevated.^60,61 Imaging may begin with a chest X-ray to assess for a mediastinal mass; however, CTs of the chest, abdomen, and pelvis provide more detail to better assess for NHL. Whole body PET/CT is considered the gold standard for assessing and staging systemic involvement. If enlarged lymph nodes are present, a biopsy can confirm the subtype of NHL.^60,61

PHYSICAL EXAMINATION

A focused physical examination may aid HCPs in early detection of the cancers associated with Camp Lejeune (Table 2). The physical examination can guide diagnostic testing and imaging for further assessment and workup for VOC-related cancers.

Proposed Diagnostic Screening Panel

Primary care and internal medicine HCPs have the opportunity to improve patient health outcomes by implementing a targeted diagnostic screening panel for identified veterans previously stationed at Camp Lejeune. Early identification of cancers associated with VOCs exposure can facilitate earlier treatment interventions and improve health and quality of life outcomes. The following diagnostic screening panel outlines a potential cost-effective strategy for evaluating and detecting the 10 cancers associated with VOC exposure in Camp Lejeune water.

Baseline Screening

Implementing a diagnostic screening panel in this high-risk cohort can lead to earlier diagnosis, reduce mortality, and improve patient outcomes through early intervention, which in turn may result in less invasive treatment. This approach may also reduce health care costs by avoiding costs associated with delayed diagnosis and advanced-stage cancer care (Tables 3 and 4).

A baseline panel of tests for exposed veterans could include:

• A CBC with differential and peripheral smear to assess for anemia, leukemia, thrombocytopenia, and blast cells associated with leukemias, MDS, multiple myeloma, and NHL.^{19,46,47,52,55,56,60,61}
• CMP evaluates calcium, total protein, renal and liver renal function. Elevated test results may indicate kidney or liver cancer or multiple myeloma.^{19,27,28,55,56}
• LDH testing may reveal levels that are elevated from tissue damage or high cell turnover in kidney cancer, multiple myeloma, and NHL.^{19,55,56,60,61}
• Urinalysis with microscopy may detect hematuria, proteinuria and cellular casts in bladder and kidney cancers.^13,24,19
• Low-dose CTs of the chest, abdomen, and pelvis are recommended for early identification of any masses or lymphadenopathy in lung, kidney, liver cancers, and NHL.^{19,27,28,32,60,61}

COST EFFICIENCY

Screening Panel Cost

According to the Medicare Clinical Laboratory Fee Schedule payment cap for 2018, the mean cost for the proposed blood workup was $35 (CBC, $10; CMP, $13; LDH, $8; urinalysis, $4).⁶² Medicare procedure price schedule for 2025 includes $351 for a CT of the abdomen and pelvis with and without contrast (Current Procedural Terminology [CPT] code 74177) and $187 for a CT of the chest with and without contrast (CPT code 71270).^63,64 The total proposed diagnostic screening panel payment cost about $572.

Cancer Care Cost

The average cost for initial cancer care across all cancer sites from 2007 to 2013 was $43,516 per patient; Camp Lejeune-associated cancers ranged from $26,443 for bladder cancer to $89,947 for esophageal cancer care.⁶⁴ Further, the last year of life cost across all cancer sites averaged $109,727, and Camp Lejeune-associated cancer types ranged from $76,101 for breast cancer to $169,588 for leukemia.⁶⁵

CONCLUSIONS

From 1953 to 1985, up to 1 million military personnel, civilian workers, and their families stationed at Camp Lejeune were unknowingly exposed to toxic and carcinogenic VOCs, which are associated with = 10 cancers, including bladder, kidney, esophageal, liver, lung, breast, and hematologic malignancies.^1-4 Some veterans may be asymptomatic, whereas others present with subtle or specific symptoms that can vary by individual and the type and stage of cancer. HCPs have an opportunity to improve patient outcomes through awareness in identifying symptoms associated with Camp Lejeune water exposure and performing a thorough baseline physical examination, especially noting lymphadenopathy, unexplained weight loss, or masses, which can guide further diagnostic evaluation. Timely screening can identify cancers earlier, reducing delays in care, mitigating the cost burden associated with advanced-stage cancer treatment, improving survival outcomes, and enhancing quality of life. Primary care and internal medicine HCPs specifically play a crucial role in early recognition, physical assessment, and appropriate screening tools. A proposed panel includes CBC with differential and peripheral smear, CMP, LDH, urinalysis, and low-dose CTs of the chest, abdomen and pelvis. Implementation should be guided by clinical judgment and patient-specific risk factors. The proposed diagnostic screening panel is a small price to pay for those who served in any capacity at Camp Lejeune.

More than 40 million surgeries are performed annually in the United States, of which > 18 million are orthopedic, including > 1 million emergency orthopedic surgeries and > 2 million joint replacements.^1-4 Notably, > 50% of patients undergoing orthopedic surgery are aged ≥ 65 years, a demographic shift driven by longer life expectancies and an increasing number of older adults remaining physically active for extended periods.⁵ Osteoarthritis, the most common joint disease, affects 10% of men and 18% of women aged > 60 years, often necessitating an orthopedic joint replacement.⁶ Perioperative morbidity and mortality are 2.9- to 6.7-times higher in older adults compared with younger adults.⁷ These risks include infection, venous thromboembolism (VTE), pressure ulcers, reduced mobility, and increased mortality. Due to the high incidence of these complications in older surgical patients, special perioperative protocols and considerations are needed when preparing an older patient for surgery. This review aims to establish concrete considerations and guidelines for perioperative management.

METHODOLOGY

A literature review of PubMed, Google Scholar, and IEEE Xplore identified research on perioperative challenges in geriatric orthopedic surgery. Keywords included geriatrics and orthopedic surgery, perioperative care in geriatric populations, and orthopedic perioperative care. Inclusion criteria were strictly defined to ensure relevance to the geriatric population, with studies focusing on patients aged ≥ 65 years. Exclusion criteria were applied to remove studies that did not involve geriatric populations or orthopedic surgeries or that lacked a clear perioperative focus. Studies were analyzed for design, interventions, and outcomes. Special attention was given to identifying common challenges and trends related to perioperative considerations. We developed a narrative report providing a comprehensive overview of the current understanding of perioperative care for geriatric orthopedic patients to offer practical recommendations for clinicians to use in their practice.

RESULTS

Consistent with the narrative review methodology described, the literature search yielded a broad range of publications addressing perioperative considerations in geriatric orthopedic patients. Articles were screened for relevance to patients aged ≥ 65 years undergoing orthopedic surgery and for applicability to perioperative optimization and postoperative outcomes. Given the heterogeneity in study design, population characteristics, and outcome reporting, findings are presented descriptively rather than being quantitatively pooled. Studies not focused on geriatric populations, orthopedic procedures, or perioperative management were excluded. Key themes included multimorbidity and comorbidity optimization, age-related physiologic changes, frailty assessment and fracture risk stratification, nutritional and bone health management, mechanism of injury considerations, prevention of postoperative complications, and the role of multidisciplinary perioperative care.

Unique Physiological Challenges

The aging process induces a range of physiological changes that can increase morbidity and mortality following surgery. One of the most essential elements to surgical recovery is wound healing, as impairments in this process can lead to adverse events, including infection, cosmetic deformity, and wound dehiscence. The general paradigm of aging involves cell senescence resulting in slower or disorganized functional capacity of these cells.⁸ While wound healing in older individuals was once thought to be defective, recent research has demonstrated that this process is not absent, but delayed.⁹

Wound healing is a tightly regulated and evolutionarily conserved process that proceeds through 3 main phases: inflammation, proliferation, and remodeling. Re-epithelialization begins with the migration of epithelial cells from hair follicles, sweat glands, or wound margins (depending on wound depth) and is influenced by oxygen levels, moisture, and growth factors.⁹ Several characteristics of aged skin contribute to the delayed healing process. Aged skin has fewer hair follicles and eccrine sweat glands, as well as decreased follicle thickness.¹⁰ This results in fewer proliferating cells for wound healing and lower amounts of sebum production for skin moisture.¹¹ Furthermore, aged fibroblasts are fewer in number and less effective in synthesizing extracellular matrices, resulting in slower and less tensile wound healing.¹² Additionally, microvascular changes associated with aging result in disorganized vasculature, which impairs oxygen delivery to the wound bed and diminishes the influx of proinflammatory cells necessary for effective healing.¹³ These senescent traits of aged skin contribute to the delayed wound healing process found in geriatric patients. 

Compounding these age-related factors is the prevalence of multimorbidity, or coexisting chronic diagnoses, in 55% to 98% of older patients.¹⁴ Common comorbidities include peripheral arterial disease, chronic venous insufficiency, type 1 and type 2 diabetes, neoplasms, atherosclerotic disease, and hypertension. Older patients are more likely to be prescribed corticosteroids and chemotherapeutic agents that impair the function of inflammatory cells necessary for wound healing.^15,16 Additionally, decreased mobility is more common in geriatric patients, which can increase the risk of wound formation, particularly pressure ulcers.¹⁷

Perioperative Considerations

All surgical patients undergo a formal or informal preoperative evaluation to assess their fitness for surgery, with the goal of minimizing both anesthesia-related risks and postoperative complications. A widely used tool in this assessment is the American Society of Anesthesiologists (ASA) physical status classification, which stratifies patients into 6 categories based on their medical history and overall health status.¹⁸ Classes range from healthy patients (Class I) to organ donors who are brain-dead (Class VI).

Cardiac optimization is an essential component of preoperative evaluation for older adults due to their higher risk of underlying cardiovascular disease.¹⁹ This process involves an in-depth review of the patient’s cardiac history, including the timing and nature of any prior interventions and the recurrence rate. Functional capacity is assessed through metabolic equivalents, where a threshold of > 4 metabolic equivalents (the ability to walk up a flight of stairs) is considered adequate for surgery. Risk is assessed based on the specific surgical procedure, and nonemergent orthopedic procedures are considered intermediate risk. If a patient is deemed high risk at any stage of this evaluation, further cardiac testing is indicated. 

Pulmonary optimization is typically necessary for geriatric patients, who are more likely to have conditions such as chronic obstructive pulmonary disease or interstitial lung disease.^14,20 In patients without severe systemic lung disease, pulmonary optimization involves assessing the functional expiratory volume and diffusing capacity for carbon monoxide. In addition, aggressive modification of risk factors, such as smoking cessation, is strongly recommended. 

Additional perioperative conditions are disease-specific and involve evaluation of comorbid illnesses and recognition of absolute contraindications to noncardiac surgery. For instance, an ejection fraction of < 35%, a history of myocardial infarction within 6 months, or active diabetic ketoacidosis are all absolute contraindications to elective surgery. For orthopedic procedures, additional contraindications include symptomatic bacteremia, active joint or local tissue infection, severe malnutrition, uncontrolled metabolic syndrome or chronic disease, untreated immunodeficiency, and active deep venous thrombosis (DVT) or pulmonary embolism.²¹

Bone Health and Nutrition

In the context of orthopedic surgery, the hallmark of clinically defined optimal bone health is a musculoskeletal system that provides the ability for pain-free functional and occupational tasks with an adequate capacity to withstand the mechanical forces imparted by everyday life. Back pain and arthritis are the fourth- and sixth-most common complaints in primary care, underscoring suboptimal bone health management in developed countries.²²

Optimizing bone health through proper nutrition is crucial in the perioperative management of geriatric orthopedic patients. The clinical diagnosis of malnutrition has well-studied associations with worse outcomes after orthopedic surgery, which include increased mortality, hospital length of stay, readmission rates, and health institution spending.^23-25 Some studies show that up to 60% of geriatric patients may be malnourished.²⁶ 

Regarding vitamin and mineral supplements, the general consensus before orthopedic surgery is that vitamins A, C, D, and E, and zinc are predictive in determining postoperative health.²⁷ However, Curtis et al state that therapy should be targeted at correcting relative deficiencies; supraphysiologic concentrations of these vitamins do not appear to be helpful.²⁷ This claim may merit serum studies to rule out deficiencies. Dietitians should be involved in the creation of a patient care plan in the spirit of multidisciplinary orthopedic surgery approaches, which have proven to result in superior patient outcomes.²⁸ Additionally, directive counseling should be provided when necessary. 

In patients with adequately managed nutrition, 7 to 10 days of diet optimization is typically sufficient, but patients with malnutrition may require sustained nutritional support for up to 6 weeks; a standardized time for adequate nutrition supplementation has not been identified.^25-27 Postoperative management is similar in older patients who are malnourished and those receiving adequate nutrition after orthopedic surgery, which typically involves 3 weeks of a high-protein diet.²⁶

Evaluating Mechanisms of Injury

Assessing the mechanism of injury (MOI) is essential to developing an appropriate and successful orthopedic treatment plan. MOI is typically categorized as low energy, which consists of ground-level falls and other minor trauma, or high energy, which can include motor vehicle crashes or falls from a height.²⁹ Unlike younger patients who typically experience trauma from high-energy MOIs, geriatric patients often sustain fractures from low-energy MOIs. The importance of assessing MOI for the geriatric population is magnified as it provides vital clues that not only help determine the nature of the injury, but also highlight underlying frailty, comorbidities, and potential complications. Weakness or deconditioning related to older age is often not discovered before trauma, which is why assessing the MOI can provide valuable information regarding overall patient health.³⁰

The MOI of trauma also is correlated with factors that influence postoperative recovery and overall prognosis (Figure). Falls comprise more than three-quarters of the MOI in geriatric patients with trauma, and > 90% of these falls are ground-level or other simple falls.³⁰ Falls secondary to an intrinsic disorder, rather than an extrinsic environmental hazard, are more common in geriatric patients.³¹ 

These events may be associated with an underlying medical condition, such as osteopenia, osteoporosis, or neuromuscular disorders, such as Parkinson disease.³² They may also be attributed to normal age-related changes, such as decreased visual acuity, reduced reaction time, or mild cognitive impairment.³⁰ An estimated 6% to 35% of geriatric patients who present to the emergency department have some degree of cognitive dysfunction.³³ Accordingly, a thorough understanding of the events leading up to injury is vital for the management of older patients. Knowing the specific circumstances of a fall can provide insight into the patient’s gait, balance, and need for further investigations such as cognitive screening or evaluation of home safety. This information can guide decisions regarding preoperative optimization of medications and postoperative rehabilitation interventions.

Frailty and Risk of Fracture

Frailty is a clinical syndrome defined by overall decreased capacity for the body’s adaptive changes to various stressors.³⁴ It is a common condition in geriatric populations due to cumulative degenerative changes and multisystem decline over a lifetime’s worth of disruptions to natural homeostasis.³⁴ In orthopedics, frailty typically refers to musculoskeletal durability and resilience in response to mechanical forces (ie, falls, trauma, and high-acceleration movements). Globally, > 200 million people have osteoporotic frailty, leading to 9 million hip fractures annually.³⁵ More than 30% of people aged ≥ 65 years fall ≥ 1 time per calendar year.³⁶

Assessing frailty in geriatric patients undergoing orthopedic surgery is vital, as it predisposes patients to higher rates of morbidity, mortality, and institutionalization, particularly from falls and resultant fragility fractures.^37-39 This is true for a wide range of orthopedic procedures, spanning elective to urgent surgeries and involving the axial and appendicular skeleton.^40,41 Given the high rates of fractures, subsequent patient morbidity, and financial burden on the health care system, effective frailty screening is essential. 

There are many strategies to assess frailty risk and subsequent fracture risk.⁴² Questionnaires or online medical calculators serve as easy-to-use tools for assessment of frailty or associated predictors of fragility fractures. Validated assessment tools are provided in Table 1. 

Dual-emission X-ray absorptiometry is a well-established way to determine bone density and establish fracture risk. The Fried Frailty Phenotype score and Short Performance Physical Battery test are clinically applicable methods of assessing frailty in older outpatient populations. Although these examinations focus on different aspects of the patient, they have moderate agreeability, are sensitive, and can be readily performed in the clinical setting as demonstrated by a > 90% patient participation rate for both methods.⁴² Finally, several serum studies can be predictive of frailty, the most readily modifiable of which are vitamin D3, ferritin, albumin, and calcium.⁴³ Although they are more invasive for the patient, serum studies can provide additional modifiable targets for perioperative optimization and contribute to risk stratification. 

Risk stratification should take place around 6 weeks before surgery, which should provide adequate time for rectification of preoperative barriers to elective surgical intervention—namely nutritional status. In cases of urgent or emergent procedures (ie, femoral neck fracture with concern for avascular necrosis of the femoral head), this may not be possible but should be conducted nonetheless for patient-specific postoperative rehabilitation and risk reduction.

Postoperative Complication Risks

Postoperative complications affect nearly 15% of geriatric orthopedic patients, highlighting the need for comprehensive preoperative evaluations to assess risk factors.⁴⁴ Age-related physiological changes, frailty, and comorbidities complicate recovery and management (Table 2).

Wound healing is impaired in older individuals due to suboptimal circulation and decreased oxygenation that is secondary to age-related changes, as well as the increased likelihood of comorbid conditions (eg, diabetes).⁷ Surgical site infections can be particularly malicious in geriatric patients, with a 4% incidence.^45,46 Hospitalization can be prolonged by a mean 2 weeks, which increases the risk of hospital-associated delirium and iatrogenic complications.⁴⁶ Both the mortality rate and costs associated with hospitalization are higher for older patients who develop surgical site infections compared with patients aged < 65 years, underscoring the importance of vigilant monitoring, early detection, and effective preoperative screening to identify and manage modifiable risk factors.⁴⁷ 

Postoperative delirium is another common complication of orthopedic surgery in the geriatric population, increasing morbidity and mortality. The incidence is reported to be as high as 53.3% in the trauma setting and 28.3% in the elective setting, indicating a need to assess patient risk preoperatively.^48,49 Several factors contribute to the high incidence of delirium, including advanced age, longer surgical durations, intraoperative hypotension and hypercapnia, pre-existing cognitive dysfunction, and postoperative sleep disorders.⁵⁰ 

VTE is another common cause of complications following orthopedic surgery. The development of DVT can lead to subsequent pulmonary embolism, which can be fatal. Orthopedic surgery patients are already at higher risk of DVT and VTE than other surgical patients, with an incidence as high as 40% to 60%, though it is frequently asymptomatic.^51,52 Geriatric patients may be more likely to have concurrent comorbidities that increase hypercoagulability.⁵³ Congestive heart failure, chronic kidney disease, and cardiovascular disease are all more common in older individuals and can increase the risk of VTE by 2-fold.⁵³ While anticoagulation is the standard of care to prevent VTE after orthopedic surgery, geriatric patients require more careful monitoring due to the higher incidence of bleeding complications. Additionally, early postoperative mobilization is critical to reduce the risk of DVT without significantly increasing pain or causing other adverse events.⁵⁴ 

Respiratory complications are common after orthopedic surgery, particularly atelectasis and bronchospasm, which can result from intraoperative mechanical ventilation.⁵⁵ While these conditions are typically self-limiting, more severe respiratory issues such as pneumonia are a significant concern because they may lead to the need for mechanical ventilation and admission to the intensive care unit (ICU). The more severe complications have an incidence of about 1% to 2% in orthopedic surgery patients.⁵⁶ Preventive strategies, such as respiratory physiotherapy and guided breathing exercises, are crucial to minimize perioperative pulmonary complications and promote optimal recovery. Addressing these challenges through early intervention is essential to improve outcomes.

Multidisciplinary Perioperative Care

Multidisciplinary care in orthopedic surgery involves collaborative management of patient care by general practitioners, surgeons, anesthesiologists, dietitians, physical and occupational therapists, inpatient health care practitioners (HCPs), and social services. The goal of this form of care is to provide a longitudinal sequence of health-optimization tactics that prepare a patient for surgery and give them the best chance of postoperative recovery.

Given that many aspects of geriatric health play a role in orthopedic postoperative outcomes, there are many preoperative factors to consider. As previously discussed, preoperative evaluation of geriatric patients should include nutritional and fragility screening to determine surgical candidacy and target modifiable risk factors for risk reduction. This screening can be conducted by primary care practitioners and orthopedic surgeons in an outpatient setting. A multidisciplinary approach benefits patients by decreasing time to surgery.³⁵ 

Several large studies have demonstrated the positive influence of a multidisciplinary approach on patient-oriented outcomes in orthopedic patients. Incorporation of this style of care in contrast to surgeon-led perioperative optimization leads to fewer floor and ICU admissions, shorter lengths of stay, and decreased mortality rates.^35,57 These findings are broadly applicable to a wide range of orthopedic surgeries and even surgeries outside of the musculoskeletal system.^58,59 In addition, this strategy has demonstrated reduced in-hospital health care costs due to shorter lengths of stay and fewer ICU admissions. Physical and occupational therapy also have irreplaceable roles in outcomes after orthopedic surgeries. They have independently been shown to decrease pain, increase range of motion, and increase functionality in daily life.⁶⁰ These aspects of recovery are essential for geriatric well-being.

Screening Tools

The World Health Organization FRAX fracture risk assessment tool (www.fraxplus.org/calculation-tool) was developed to identify patients at high risk of fracture and subsequent complications and to guide clinical decision-making regarding pharmacologic interventions.⁶¹ FRAX calculates the 10-year probability of fracture based on demographic factors, such as age and body mass index, clinical measures (eg, femoral neck bone mineral density), and risk factors (eg, prior fragility fractures, substance use history, and prolonged glucocorticoid use).⁶¹ The online tool is easy to use, making it a valuable resource for assessing fracture risk and determining appropriate treatment strategies.

The fatigue, resistance, ambulation, illnesses, loss of weight (FRAIL) scale assesses frailty in older adults. The scale classifies patients into 3 categories: robust, prefrail, and frail. The frail category is associated with an increased frequency of hip fracture and an elevated ASA class.⁶² Additionally, the FRAIL scale has demonstrated value in predicting hospital length of stay and the risk of postoperative complications.⁶² It also has shown utility in quantifying frailty status, which is traditionally challenging to assess systematically.⁶³

The Mini-Cog is commonly used in geriatric populations to screen for cognitive impairment. Preoperative Mini-Cog screening has been shown to predict the development of postoperative complications.⁶⁴ Geriatric patients who screened positive for cognitive impairment prior to orthopedic surgery were more likely to develop postoperative delirium, require alternative discharge disposition, and have a longer hospital length of stay.⁶⁴ Mini-Cog serves as an important preoperative tool for identifying patients who may benefit from closer postoperative monitoring and tailored care.

The Comprehensive Geriatric Assessment (CGA) is a multidimensional evaluation that has been validated for use in geriatric patients undergoing orthopedic surgery.⁶⁵ The CGA assesses functional status and the ability to perform activities of daily living (ADLs), such as eating, dressing, and ambulating. Poor ADLs are associated with increased risk of falls and cardiopulmonary complications. The CGA allows HCPs to identify patients at higher risk of complications and tailor interventions that optimize functional recovery during the perioperative period.

Nutritional screening is another component of preoperative evaluation in older adults undergoing orthopedic surgery. The Perioperative Nutrition Screen is a preoperative phone assessment of unintentional weight loss in the past 6 months.⁶⁶ Patients who screen positive are asked to come in for a preoperative visit with a registered dietitian who can further evaluate the nutritional status of the patient. 

The Mini Nutritional Assessment Short Form (MNA-SF), Malnutrition Universal Screening Tool, and Nutrition Risk Screening 2002 have all been validated for use in older patients undergoing orthopedic surgery. Among these, the MNA-SF has demonstrated superior utility in predicting hospital readmission and mortality.⁶⁷ Given the established links between malnutrition and poor surgical outcomes, routine nutritional screening is important for identifying geriatric patients who may require preoperative nutritional interventions.

CONCLUSIONS AND RECOMMENDATIONS

Perioperative management of geriatric patients undergoing orthopedic surgery requires an assessment and strategy focused on risk stratification, patient optimization, and mitigation of potential complications and mortality. Due to the complexity and comprehensive nature of an optimal perioperative plan, creating the plan early is essential to ensure adequate time for patient optimization and care coordination.

Nutrition plays a critical role in the success of surgical procedures, and orthopedics is no exception. Extra care should be taken to preoperatively optimize patient bone health before surgical intervention to enhance recovery and reduce the risk of complications. After an appropriate patient history and clinical picture are gathered, screening tools should be used on a case-by-case basis to further characterize comorbid conditions that may contribute to suboptimal outcomes. Additionally, given the proven association between frailty and fracture risk, frailty serves as a readily quantifiable predictor of patient-oriented outcomes. This should be assessed preoperatively with appropriate risk-stratification tools to determine appropriate postoperative measures to prevent morbidity and mortality. 

Orthopedic surgery is increasingly common in geriatric patients, who face higher perioperative risks due to age-related physiological changes, multimorbidity, and frailty. Optimizing preoperative assessment and adopting a multidisciplinary approach—integrating surgeons, anesthesiologists, physical therapists, and dietitians—can improve outcomes, reduce complications, and enhance recovery. The successful use of the tools and strategies outlined in this article by primary care should facilitate access to and recovery from orthopedic surgery in the geriatric population.

More than 40 million surgeries are performed annually in the United States, of which > 18 million are orthopedic, including > 1 million emergency orthopedic surgeries and > 2 million joint replacements.^1-4 Notably, > 50% of patients undergoing orthopedic surgery are aged ≥ 65 years, a demographic shift driven by longer life expectancies and an increasing number of older adults remaining physically active for extended periods.⁵ Osteoarthritis, the most common joint disease, affects 10% of men and 18% of women aged > 60 years, often necessitating an orthopedic joint replacement.⁶ Perioperative morbidity and mortality are 2.9- to 6.7-times higher in older adults compared with younger adults.⁷ These risks include infection, venous thromboembolism (VTE), pressure ulcers, reduced mobility, and increased mortality. Due to the high incidence of these complications in older surgical patients, special perioperative protocols and considerations are needed when preparing an older patient for surgery. This review aims to establish concrete considerations and guidelines for perioperative management.

METHODOLOGY

A literature review of PubMed, Google Scholar, and IEEE Xplore identified research on perioperative challenges in geriatric orthopedic surgery. Keywords included geriatrics and orthopedic surgery, perioperative care in geriatric populations, and orthopedic perioperative care. Inclusion criteria were strictly defined to ensure relevance to the geriatric population, with studies focusing on patients aged ≥ 65 years. Exclusion criteria were applied to remove studies that did not involve geriatric populations or orthopedic surgeries or that lacked a clear perioperative focus. Studies were analyzed for design, interventions, and outcomes. Special attention was given to identifying common challenges and trends related to perioperative considerations. We developed a narrative report providing a comprehensive overview of the current understanding of perioperative care for geriatric orthopedic patients to offer practical recommendations for clinicians to use in their practice.

RESULTS

Consistent with the narrative review methodology described, the literature search yielded a broad range of publications addressing perioperative considerations in geriatric orthopedic patients. Articles were screened for relevance to patients aged ≥ 65 years undergoing orthopedic surgery and for applicability to perioperative optimization and postoperative outcomes. Given the heterogeneity in study design, population characteristics, and outcome reporting, findings are presented descriptively rather than being quantitatively pooled. Studies not focused on geriatric populations, orthopedic procedures, or perioperative management were excluded. Key themes included multimorbidity and comorbidity optimization, age-related physiologic changes, frailty assessment and fracture risk stratification, nutritional and bone health management, mechanism of injury considerations, prevention of postoperative complications, and the role of multidisciplinary perioperative care.

Unique Physiological Challenges

The aging process induces a range of physiological changes that can increase morbidity and mortality following surgery. One of the most essential elements to surgical recovery is wound healing, as impairments in this process can lead to adverse events, including infection, cosmetic deformity, and wound dehiscence. The general paradigm of aging involves cell senescence resulting in slower or disorganized functional capacity of these cells.⁸ While wound healing in older individuals was once thought to be defective, recent research has demonstrated that this process is not absent, but delayed.⁹

Wound healing is a tightly regulated and evolutionarily conserved process that proceeds through 3 main phases: inflammation, proliferation, and remodeling. Re-epithelialization begins with the migration of epithelial cells from hair follicles, sweat glands, or wound margins (depending on wound depth) and is influenced by oxygen levels, moisture, and growth factors.⁹ Several characteristics of aged skin contribute to the delayed healing process. Aged skin has fewer hair follicles and eccrine sweat glands, as well as decreased follicle thickness.¹⁰ This results in fewer proliferating cells for wound healing and lower amounts of sebum production for skin moisture.¹¹ Furthermore, aged fibroblasts are fewer in number and less effective in synthesizing extracellular matrices, resulting in slower and less tensile wound healing.¹² Additionally, microvascular changes associated with aging result in disorganized vasculature, which impairs oxygen delivery to the wound bed and diminishes the influx of proinflammatory cells necessary for effective healing.¹³ These senescent traits of aged skin contribute to the delayed wound healing process found in geriatric patients. 

Compounding these age-related factors is the prevalence of multimorbidity, or coexisting chronic diagnoses, in 55% to 98% of older patients.¹⁴ Common comorbidities include peripheral arterial disease, chronic venous insufficiency, type 1 and type 2 diabetes, neoplasms, atherosclerotic disease, and hypertension. Older patients are more likely to be prescribed corticosteroids and chemotherapeutic agents that impair the function of inflammatory cells necessary for wound healing.^15,16 Additionally, decreased mobility is more common in geriatric patients, which can increase the risk of wound formation, particularly pressure ulcers.¹⁷

Perioperative Considerations

All surgical patients undergo a formal or informal preoperative evaluation to assess their fitness for surgery, with the goal of minimizing both anesthesia-related risks and postoperative complications. A widely used tool in this assessment is the American Society of Anesthesiologists (ASA) physical status classification, which stratifies patients into 6 categories based on their medical history and overall health status.¹⁸ Classes range from healthy patients (Class I) to organ donors who are brain-dead (Class VI).

Cardiac optimization is an essential component of preoperative evaluation for older adults due to their higher risk of underlying cardiovascular disease.¹⁹ This process involves an in-depth review of the patient’s cardiac history, including the timing and nature of any prior interventions and the recurrence rate. Functional capacity is assessed through metabolic equivalents, where a threshold of > 4 metabolic equivalents (the ability to walk up a flight of stairs) is considered adequate for surgery. Risk is assessed based on the specific surgical procedure, and nonemergent orthopedic procedures are considered intermediate risk. If a patient is deemed high risk at any stage of this evaluation, further cardiac testing is indicated. 

Pulmonary optimization is typically necessary for geriatric patients, who are more likely to have conditions such as chronic obstructive pulmonary disease or interstitial lung disease.^14,20 In patients without severe systemic lung disease, pulmonary optimization involves assessing the functional expiratory volume and diffusing capacity for carbon monoxide. In addition, aggressive modification of risk factors, such as smoking cessation, is strongly recommended. 

Additional perioperative conditions are disease-specific and involve evaluation of comorbid illnesses and recognition of absolute contraindications to noncardiac surgery. For instance, an ejection fraction of < 35%, a history of myocardial infarction within 6 months, or active diabetic ketoacidosis are all absolute contraindications to elective surgery. For orthopedic procedures, additional contraindications include symptomatic bacteremia, active joint or local tissue infection, severe malnutrition, uncontrolled metabolic syndrome or chronic disease, untreated immunodeficiency, and active deep venous thrombosis (DVT) or pulmonary embolism.²¹

Bone Health and Nutrition

In the context of orthopedic surgery, the hallmark of clinically defined optimal bone health is a musculoskeletal system that provides the ability for pain-free functional and occupational tasks with an adequate capacity to withstand the mechanical forces imparted by everyday life. Back pain and arthritis are the fourth- and sixth-most common complaints in primary care, underscoring suboptimal bone health management in developed countries.²²

Optimizing bone health through proper nutrition is crucial in the perioperative management of geriatric orthopedic patients. The clinical diagnosis of malnutrition has well-studied associations with worse outcomes after orthopedic surgery, which include increased mortality, hospital length of stay, readmission rates, and health institution spending.^23-25 Some studies show that up to 60% of geriatric patients may be malnourished.²⁶ 

Regarding vitamin and mineral supplements, the general consensus before orthopedic surgery is that vitamins A, C, D, and E, and zinc are predictive in determining postoperative health.²⁷ However, Curtis et al state that therapy should be targeted at correcting relative deficiencies; supraphysiologic concentrations of these vitamins do not appear to be helpful.²⁷ This claim may merit serum studies to rule out deficiencies. Dietitians should be involved in the creation of a patient care plan in the spirit of multidisciplinary orthopedic surgery approaches, which have proven to result in superior patient outcomes.²⁸ Additionally, directive counseling should be provided when necessary. 

In patients with adequately managed nutrition, 7 to 10 days of diet optimization is typically sufficient, but patients with malnutrition may require sustained nutritional support for up to 6 weeks; a standardized time for adequate nutrition supplementation has not been identified.^25-27 Postoperative management is similar in older patients who are malnourished and those receiving adequate nutrition after orthopedic surgery, which typically involves 3 weeks of a high-protein diet.²⁶

Evaluating Mechanisms of Injury

Assessing the mechanism of injury (MOI) is essential to developing an appropriate and successful orthopedic treatment plan. MOI is typically categorized as low energy, which consists of ground-level falls and other minor trauma, or high energy, which can include motor vehicle crashes or falls from a height.²⁹ Unlike younger patients who typically experience trauma from high-energy MOIs, geriatric patients often sustain fractures from low-energy MOIs. The importance of assessing MOI for the geriatric population is magnified as it provides vital clues that not only help determine the nature of the injury, but also highlight underlying frailty, comorbidities, and potential complications. Weakness or deconditioning related to older age is often not discovered before trauma, which is why assessing the MOI can provide valuable information regarding overall patient health.³⁰

The MOI of trauma also is correlated with factors that influence postoperative recovery and overall prognosis (Figure). Falls comprise more than three-quarters of the MOI in geriatric patients with trauma, and > 90% of these falls are ground-level or other simple falls.³⁰ Falls secondary to an intrinsic disorder, rather than an extrinsic environmental hazard, are more common in geriatric patients.³¹ 

These events may be associated with an underlying medical condition, such as osteopenia, osteoporosis, or neuromuscular disorders, such as Parkinson disease.³² They may also be attributed to normal age-related changes, such as decreased visual acuity, reduced reaction time, or mild cognitive impairment.³⁰ An estimated 6% to 35% of geriatric patients who present to the emergency department have some degree of cognitive dysfunction.³³ Accordingly, a thorough understanding of the events leading up to injury is vital for the management of older patients. Knowing the specific circumstances of a fall can provide insight into the patient’s gait, balance, and need for further investigations such as cognitive screening or evaluation of home safety. This information can guide decisions regarding preoperative optimization of medications and postoperative rehabilitation interventions.

Frailty and Risk of Fracture

Frailty is a clinical syndrome defined by overall decreased capacity for the body’s adaptive changes to various stressors.³⁴ It is a common condition in geriatric populations due to cumulative degenerative changes and multisystem decline over a lifetime’s worth of disruptions to natural homeostasis.³⁴ In orthopedics, frailty typically refers to musculoskeletal durability and resilience in response to mechanical forces (ie, falls, trauma, and high-acceleration movements). Globally, > 200 million people have osteoporotic frailty, leading to 9 million hip fractures annually.³⁵ More than 30% of people aged ≥ 65 years fall ≥ 1 time per calendar year.³⁶

Assessing frailty in geriatric patients undergoing orthopedic surgery is vital, as it predisposes patients to higher rates of morbidity, mortality, and institutionalization, particularly from falls and resultant fragility fractures.^37-39 This is true for a wide range of orthopedic procedures, spanning elective to urgent surgeries and involving the axial and appendicular skeleton.^40,41 Given the high rates of fractures, subsequent patient morbidity, and financial burden on the health care system, effective frailty screening is essential. 

There are many strategies to assess frailty risk and subsequent fracture risk.⁴² Questionnaires or online medical calculators serve as easy-to-use tools for assessment of frailty or associated predictors of fragility fractures. Validated assessment tools are provided in Table 1. 

Dual-emission X-ray absorptiometry is a well-established way to determine bone density and establish fracture risk. The Fried Frailty Phenotype score and Short Performance Physical Battery test are clinically applicable methods of assessing frailty in older outpatient populations. Although these examinations focus on different aspects of the patient, they have moderate agreeability, are sensitive, and can be readily performed in the clinical setting as demonstrated by a > 90% patient participation rate for both methods.⁴² Finally, several serum studies can be predictive of frailty, the most readily modifiable of which are vitamin D3, ferritin, albumin, and calcium.⁴³ Although they are more invasive for the patient, serum studies can provide additional modifiable targets for perioperative optimization and contribute to risk stratification. 

Risk stratification should take place around 6 weeks before surgery, which should provide adequate time for rectification of preoperative barriers to elective surgical intervention—namely nutritional status. In cases of urgent or emergent procedures (ie, femoral neck fracture with concern for avascular necrosis of the femoral head), this may not be possible but should be conducted nonetheless for patient-specific postoperative rehabilitation and risk reduction.

Postoperative Complication Risks

Postoperative complications affect nearly 15% of geriatric orthopedic patients, highlighting the need for comprehensive preoperative evaluations to assess risk factors.⁴⁴ Age-related physiological changes, frailty, and comorbidities complicate recovery and management (Table 2).

Wound healing is impaired in older individuals due to suboptimal circulation and decreased oxygenation that is secondary to age-related changes, as well as the increased likelihood of comorbid conditions (eg, diabetes).⁷ Surgical site infections can be particularly malicious in geriatric patients, with a 4% incidence.^45,46 Hospitalization can be prolonged by a mean 2 weeks, which increases the risk of hospital-associated delirium and iatrogenic complications.⁴⁶ Both the mortality rate and costs associated with hospitalization are higher for older patients who develop surgical site infections compared with patients aged < 65 years, underscoring the importance of vigilant monitoring, early detection, and effective preoperative screening to identify and manage modifiable risk factors.⁴⁷ 

Postoperative delirium is another common complication of orthopedic surgery in the geriatric population, increasing morbidity and mortality. The incidence is reported to be as high as 53.3% in the trauma setting and 28.3% in the elective setting, indicating a need to assess patient risk preoperatively.^48,49 Several factors contribute to the high incidence of delirium, including advanced age, longer surgical durations, intraoperative hypotension and hypercapnia, pre-existing cognitive dysfunction, and postoperative sleep disorders.⁵⁰ 

VTE is another common cause of complications following orthopedic surgery. The development of DVT can lead to subsequent pulmonary embolism, which can be fatal. Orthopedic surgery patients are already at higher risk of DVT and VTE than other surgical patients, with an incidence as high as 40% to 60%, though it is frequently asymptomatic.^51,52 Geriatric patients may be more likely to have concurrent comorbidities that increase hypercoagulability.⁵³ Congestive heart failure, chronic kidney disease, and cardiovascular disease are all more common in older individuals and can increase the risk of VTE by 2-fold.⁵³ While anticoagulation is the standard of care to prevent VTE after orthopedic surgery, geriatric patients require more careful monitoring due to the higher incidence of bleeding complications. Additionally, early postoperative mobilization is critical to reduce the risk of DVT without significantly increasing pain or causing other adverse events.⁵⁴ 

Respiratory complications are common after orthopedic surgery, particularly atelectasis and bronchospasm, which can result from intraoperative mechanical ventilation.⁵⁵ While these conditions are typically self-limiting, more severe respiratory issues such as pneumonia are a significant concern because they may lead to the need for mechanical ventilation and admission to the intensive care unit (ICU). The more severe complications have an incidence of about 1% to 2% in orthopedic surgery patients.⁵⁶ Preventive strategies, such as respiratory physiotherapy and guided breathing exercises, are crucial to minimize perioperative pulmonary complications and promote optimal recovery. Addressing these challenges through early intervention is essential to improve outcomes.

Multidisciplinary Perioperative Care

Multidisciplinary care in orthopedic surgery involves collaborative management of patient care by general practitioners, surgeons, anesthesiologists, dietitians, physical and occupational therapists, inpatient health care practitioners (HCPs), and social services. The goal of this form of care is to provide a longitudinal sequence of health-optimization tactics that prepare a patient for surgery and give them the best chance of postoperative recovery.

Given that many aspects of geriatric health play a role in orthopedic postoperative outcomes, there are many preoperative factors to consider. As previously discussed, preoperative evaluation of geriatric patients should include nutritional and fragility screening to determine surgical candidacy and target modifiable risk factors for risk reduction. This screening can be conducted by primary care practitioners and orthopedic surgeons in an outpatient setting. A multidisciplinary approach benefits patients by decreasing time to surgery.³⁵ 

Several large studies have demonstrated the positive influence of a multidisciplinary approach on patient-oriented outcomes in orthopedic patients. Incorporation of this style of care in contrast to surgeon-led perioperative optimization leads to fewer floor and ICU admissions, shorter lengths of stay, and decreased mortality rates.^35,57 These findings are broadly applicable to a wide range of orthopedic surgeries and even surgeries outside of the musculoskeletal system.^58,59 In addition, this strategy has demonstrated reduced in-hospital health care costs due to shorter lengths of stay and fewer ICU admissions. Physical and occupational therapy also have irreplaceable roles in outcomes after orthopedic surgeries. They have independently been shown to decrease pain, increase range of motion, and increase functionality in daily life.⁶⁰ These aspects of recovery are essential for geriatric well-being.

Screening Tools

The World Health Organization FRAX fracture risk assessment tool (www.fraxplus.org/calculation-tool) was developed to identify patients at high risk of fracture and subsequent complications and to guide clinical decision-making regarding pharmacologic interventions.⁶¹ FRAX calculates the 10-year probability of fracture based on demographic factors, such as age and body mass index, clinical measures (eg, femoral neck bone mineral density), and risk factors (eg, prior fragility fractures, substance use history, and prolonged glucocorticoid use).⁶¹ The online tool is easy to use, making it a valuable resource for assessing fracture risk and determining appropriate treatment strategies.

The fatigue, resistance, ambulation, illnesses, loss of weight (FRAIL) scale assesses frailty in older adults. The scale classifies patients into 3 categories: robust, prefrail, and frail. The frail category is associated with an increased frequency of hip fracture and an elevated ASA class.⁶² Additionally, the FRAIL scale has demonstrated value in predicting hospital length of stay and the risk of postoperative complications.⁶² It also has shown utility in quantifying frailty status, which is traditionally challenging to assess systematically.⁶³

The Mini-Cog is commonly used in geriatric populations to screen for cognitive impairment. Preoperative Mini-Cog screening has been shown to predict the development of postoperative complications.⁶⁴ Geriatric patients who screened positive for cognitive impairment prior to orthopedic surgery were more likely to develop postoperative delirium, require alternative discharge disposition, and have a longer hospital length of stay.⁶⁴ Mini-Cog serves as an important preoperative tool for identifying patients who may benefit from closer postoperative monitoring and tailored care.

The Comprehensive Geriatric Assessment (CGA) is a multidimensional evaluation that has been validated for use in geriatric patients undergoing orthopedic surgery.⁶⁵ The CGA assesses functional status and the ability to perform activities of daily living (ADLs), such as eating, dressing, and ambulating. Poor ADLs are associated with increased risk of falls and cardiopulmonary complications. The CGA allows HCPs to identify patients at higher risk of complications and tailor interventions that optimize functional recovery during the perioperative period.

Nutritional screening is another component of preoperative evaluation in older adults undergoing orthopedic surgery. The Perioperative Nutrition Screen is a preoperative phone assessment of unintentional weight loss in the past 6 months.⁶⁶ Patients who screen positive are asked to come in for a preoperative visit with a registered dietitian who can further evaluate the nutritional status of the patient. 

The Mini Nutritional Assessment Short Form (MNA-SF), Malnutrition Universal Screening Tool, and Nutrition Risk Screening 2002 have all been validated for use in older patients undergoing orthopedic surgery. Among these, the MNA-SF has demonstrated superior utility in predicting hospital readmission and mortality.⁶⁷ Given the established links between malnutrition and poor surgical outcomes, routine nutritional screening is important for identifying geriatric patients who may require preoperative nutritional interventions.

CONCLUSIONS AND RECOMMENDATIONS

Perioperative management of geriatric patients undergoing orthopedic surgery requires an assessment and strategy focused on risk stratification, patient optimization, and mitigation of potential complications and mortality. Due to the complexity and comprehensive nature of an optimal perioperative plan, creating the plan early is essential to ensure adequate time for patient optimization and care coordination.

Nutrition plays a critical role in the success of surgical procedures, and orthopedics is no exception. Extra care should be taken to preoperatively optimize patient bone health before surgical intervention to enhance recovery and reduce the risk of complications. After an appropriate patient history and clinical picture are gathered, screening tools should be used on a case-by-case basis to further characterize comorbid conditions that may contribute to suboptimal outcomes. Additionally, given the proven association between frailty and fracture risk, frailty serves as a readily quantifiable predictor of patient-oriented outcomes. This should be assessed preoperatively with appropriate risk-stratification tools to determine appropriate postoperative measures to prevent morbidity and mortality. 

Orthopedic surgery is increasingly common in geriatric patients, who face higher perioperative risks due to age-related physiological changes, multimorbidity, and frailty. Optimizing preoperative assessment and adopting a multidisciplinary approach—integrating surgeons, anesthesiologists, physical therapists, and dietitians—can improve outcomes, reduce complications, and enhance recovery. The successful use of the tools and strategies outlined in this article by primary care should facilitate access to and recovery from orthopedic surgery in the geriatric population.

More than 40 million surgeries are performed annually in the United States, of which > 18 million are orthopedic, including > 1 million emergency orthopedic surgeries and > 2 million joint replacements.^1-4 Notably, > 50% of patients undergoing orthopedic surgery are aged ≥ 65 years, a demographic shift driven by longer life expectancies and an increasing number of older adults remaining physically active for extended periods.⁵ Osteoarthritis, the most common joint disease, affects 10% of men and 18% of women aged > 60 years, often necessitating an orthopedic joint replacement.⁶ Perioperative morbidity and mortality are 2.9- to 6.7-times higher in older adults compared with younger adults.⁷ These risks include infection, venous thromboembolism (VTE), pressure ulcers, reduced mobility, and increased mortality. Due to the high incidence of these complications in older surgical patients, special perioperative protocols and considerations are needed when preparing an older patient for surgery. This review aims to establish concrete considerations and guidelines for perioperative management.

METHODOLOGY

A literature review of PubMed, Google Scholar, and IEEE Xplore identified research on perioperative challenges in geriatric orthopedic surgery. Keywords included geriatrics and orthopedic surgery, perioperative care in geriatric populations, and orthopedic perioperative care. Inclusion criteria were strictly defined to ensure relevance to the geriatric population, with studies focusing on patients aged ≥ 65 years. Exclusion criteria were applied to remove studies that did not involve geriatric populations or orthopedic surgeries or that lacked a clear perioperative focus. Studies were analyzed for design, interventions, and outcomes. Special attention was given to identifying common challenges and trends related to perioperative considerations. We developed a narrative report providing a comprehensive overview of the current understanding of perioperative care for geriatric orthopedic patients to offer practical recommendations for clinicians to use in their practice.

RESULTS

Consistent with the narrative review methodology described, the literature search yielded a broad range of publications addressing perioperative considerations in geriatric orthopedic patients. Articles were screened for relevance to patients aged ≥ 65 years undergoing orthopedic surgery and for applicability to perioperative optimization and postoperative outcomes. Given the heterogeneity in study design, population characteristics, and outcome reporting, findings are presented descriptively rather than being quantitatively pooled. Studies not focused on geriatric populations, orthopedic procedures, or perioperative management were excluded. Key themes included multimorbidity and comorbidity optimization, age-related physiologic changes, frailty assessment and fracture risk stratification, nutritional and bone health management, mechanism of injury considerations, prevention of postoperative complications, and the role of multidisciplinary perioperative care.

Unique Physiological Challenges

The aging process induces a range of physiological changes that can increase morbidity and mortality following surgery. One of the most essential elements to surgical recovery is wound healing, as impairments in this process can lead to adverse events, including infection, cosmetic deformity, and wound dehiscence. The general paradigm of aging involves cell senescence resulting in slower or disorganized functional capacity of these cells.⁸ While wound healing in older individuals was once thought to be defective, recent research has demonstrated that this process is not absent, but delayed.⁹

Wound healing is a tightly regulated and evolutionarily conserved process that proceeds through 3 main phases: inflammation, proliferation, and remodeling. Re-epithelialization begins with the migration of epithelial cells from hair follicles, sweat glands, or wound margins (depending on wound depth) and is influenced by oxygen levels, moisture, and growth factors.⁹ Several characteristics of aged skin contribute to the delayed healing process. Aged skin has fewer hair follicles and eccrine sweat glands, as well as decreased follicle thickness.¹⁰ This results in fewer proliferating cells for wound healing and lower amounts of sebum production for skin moisture.¹¹ Furthermore, aged fibroblasts are fewer in number and less effective in synthesizing extracellular matrices, resulting in slower and less tensile wound healing.¹² Additionally, microvascular changes associated with aging result in disorganized vasculature, which impairs oxygen delivery to the wound bed and diminishes the influx of proinflammatory cells necessary for effective healing.¹³ These senescent traits of aged skin contribute to the delayed wound healing process found in geriatric patients. 

Compounding these age-related factors is the prevalence of multimorbidity, or coexisting chronic diagnoses, in 55% to 98% of older patients.¹⁴ Common comorbidities include peripheral arterial disease, chronic venous insufficiency, type 1 and type 2 diabetes, neoplasms, atherosclerotic disease, and hypertension. Older patients are more likely to be prescribed corticosteroids and chemotherapeutic agents that impair the function of inflammatory cells necessary for wound healing.^15,16 Additionally, decreased mobility is more common in geriatric patients, which can increase the risk of wound formation, particularly pressure ulcers.¹⁷

Perioperative Considerations

All surgical patients undergo a formal or informal preoperative evaluation to assess their fitness for surgery, with the goal of minimizing both anesthesia-related risks and postoperative complications. A widely used tool in this assessment is the American Society of Anesthesiologists (ASA) physical status classification, which stratifies patients into 6 categories based on their medical history and overall health status.¹⁸ Classes range from healthy patients (Class I) to organ donors who are brain-dead (Class VI).

Cardiac optimization is an essential component of preoperative evaluation for older adults due to their higher risk of underlying cardiovascular disease.¹⁹ This process involves an in-depth review of the patient’s cardiac history, including the timing and nature of any prior interventions and the recurrence rate. Functional capacity is assessed through metabolic equivalents, where a threshold of > 4 metabolic equivalents (the ability to walk up a flight of stairs) is considered adequate for surgery. Risk is assessed based on the specific surgical procedure, and nonemergent orthopedic procedures are considered intermediate risk. If a patient is deemed high risk at any stage of this evaluation, further cardiac testing is indicated. 

Pulmonary optimization is typically necessary for geriatric patients, who are more likely to have conditions such as chronic obstructive pulmonary disease or interstitial lung disease.^14,20 In patients without severe systemic lung disease, pulmonary optimization involves assessing the functional expiratory volume and diffusing capacity for carbon monoxide. In addition, aggressive modification of risk factors, such as smoking cessation, is strongly recommended. 

Additional perioperative conditions are disease-specific and involve evaluation of comorbid illnesses and recognition of absolute contraindications to noncardiac surgery. For instance, an ejection fraction of < 35%, a history of myocardial infarction within 6 months, or active diabetic ketoacidosis are all absolute contraindications to elective surgery. For orthopedic procedures, additional contraindications include symptomatic bacteremia, active joint or local tissue infection, severe malnutrition, uncontrolled metabolic syndrome or chronic disease, untreated immunodeficiency, and active deep venous thrombosis (DVT) or pulmonary embolism.²¹

Bone Health and Nutrition

In the context of orthopedic surgery, the hallmark of clinically defined optimal bone health is a musculoskeletal system that provides the ability for pain-free functional and occupational tasks with an adequate capacity to withstand the mechanical forces imparted by everyday life. Back pain and arthritis are the fourth- and sixth-most common complaints in primary care, underscoring suboptimal bone health management in developed countries.²²

Optimizing bone health through proper nutrition is crucial in the perioperative management of geriatric orthopedic patients. The clinical diagnosis of malnutrition has well-studied associations with worse outcomes after orthopedic surgery, which include increased mortality, hospital length of stay, readmission rates, and health institution spending.^23-25 Some studies show that up to 60% of geriatric patients may be malnourished.²⁶ 

Regarding vitamin and mineral supplements, the general consensus before orthopedic surgery is that vitamins A, C, D, and E, and zinc are predictive in determining postoperative health.²⁷ However, Curtis et al state that therapy should be targeted at correcting relative deficiencies; supraphysiologic concentrations of these vitamins do not appear to be helpful.²⁷ This claim may merit serum studies to rule out deficiencies. Dietitians should be involved in the creation of a patient care plan in the spirit of multidisciplinary orthopedic surgery approaches, which have proven to result in superior patient outcomes.²⁸ Additionally, directive counseling should be provided when necessary. 

In patients with adequately managed nutrition, 7 to 10 days of diet optimization is typically sufficient, but patients with malnutrition may require sustained nutritional support for up to 6 weeks; a standardized time for adequate nutrition supplementation has not been identified.^25-27 Postoperative management is similar in older patients who are malnourished and those receiving adequate nutrition after orthopedic surgery, which typically involves 3 weeks of a high-protein diet.²⁶

Evaluating Mechanisms of Injury

Assessing the mechanism of injury (MOI) is essential to developing an appropriate and successful orthopedic treatment plan. MOI is typically categorized as low energy, which consists of ground-level falls and other minor trauma, or high energy, which can include motor vehicle crashes or falls from a height.²⁹ Unlike younger patients who typically experience trauma from high-energy MOIs, geriatric patients often sustain fractures from low-energy MOIs. The importance of assessing MOI for the geriatric population is magnified as it provides vital clues that not only help determine the nature of the injury, but also highlight underlying frailty, comorbidities, and potential complications. Weakness or deconditioning related to older age is often not discovered before trauma, which is why assessing the MOI can provide valuable information regarding overall patient health.³⁰

The MOI of trauma also is correlated with factors that influence postoperative recovery and overall prognosis (Figure). Falls comprise more than three-quarters of the MOI in geriatric patients with trauma, and > 90% of these falls are ground-level or other simple falls.³⁰ Falls secondary to an intrinsic disorder, rather than an extrinsic environmental hazard, are more common in geriatric patients.³¹ 

These events may be associated with an underlying medical condition, such as osteopenia, osteoporosis, or neuromuscular disorders, such as Parkinson disease.³² They may also be attributed to normal age-related changes, such as decreased visual acuity, reduced reaction time, or mild cognitive impairment.³⁰ An estimated 6% to 35% of geriatric patients who present to the emergency department have some degree of cognitive dysfunction.³³ Accordingly, a thorough understanding of the events leading up to injury is vital for the management of older patients. Knowing the specific circumstances of a fall can provide insight into the patient’s gait, balance, and need for further investigations such as cognitive screening or evaluation of home safety. This information can guide decisions regarding preoperative optimization of medications and postoperative rehabilitation interventions.

Frailty and Risk of Fracture

Frailty is a clinical syndrome defined by overall decreased capacity for the body’s adaptive changes to various stressors.³⁴ It is a common condition in geriatric populations due to cumulative degenerative changes and multisystem decline over a lifetime’s worth of disruptions to natural homeostasis.³⁴ In orthopedics, frailty typically refers to musculoskeletal durability and resilience in response to mechanical forces (ie, falls, trauma, and high-acceleration movements). Globally, > 200 million people have osteoporotic frailty, leading to 9 million hip fractures annually.³⁵ More than 30% of people aged ≥ 65 years fall ≥ 1 time per calendar year.³⁶

Assessing frailty in geriatric patients undergoing orthopedic surgery is vital, as it predisposes patients to higher rates of morbidity, mortality, and institutionalization, particularly from falls and resultant fragility fractures.^37-39 This is true for a wide range of orthopedic procedures, spanning elective to urgent surgeries and involving the axial and appendicular skeleton.^40,41 Given the high rates of fractures, subsequent patient morbidity, and financial burden on the health care system, effective frailty screening is essential. 

There are many strategies to assess frailty risk and subsequent fracture risk.⁴² Questionnaires or online medical calculators serve as easy-to-use tools for assessment of frailty or associated predictors of fragility fractures. Validated assessment tools are provided in Table 1. 

Dual-emission X-ray absorptiometry is a well-established way to determine bone density and establish fracture risk. The Fried Frailty Phenotype score and Short Performance Physical Battery test are clinically applicable methods of assessing frailty in older outpatient populations. Although these examinations focus on different aspects of the patient, they have moderate agreeability, are sensitive, and can be readily performed in the clinical setting as demonstrated by a > 90% patient participation rate for both methods.⁴² Finally, several serum studies can be predictive of frailty, the most readily modifiable of which are vitamin D3, ferritin, albumin, and calcium.⁴³ Although they are more invasive for the patient, serum studies can provide additional modifiable targets for perioperative optimization and contribute to risk stratification. 

Risk stratification should take place around 6 weeks before surgery, which should provide adequate time for rectification of preoperative barriers to elective surgical intervention—namely nutritional status. In cases of urgent or emergent procedures (ie, femoral neck fracture with concern for avascular necrosis of the femoral head), this may not be possible but should be conducted nonetheless for patient-specific postoperative rehabilitation and risk reduction.

Postoperative Complication Risks

Postoperative complications affect nearly 15% of geriatric orthopedic patients, highlighting the need for comprehensive preoperative evaluations to assess risk factors.⁴⁴ Age-related physiological changes, frailty, and comorbidities complicate recovery and management (Table 2).

Wound healing is impaired in older individuals due to suboptimal circulation and decreased oxygenation that is secondary to age-related changes, as well as the increased likelihood of comorbid conditions (eg, diabetes).⁷ Surgical site infections can be particularly malicious in geriatric patients, with a 4% incidence.^45,46 Hospitalization can be prolonged by a mean 2 weeks, which increases the risk of hospital-associated delirium and iatrogenic complications.⁴⁶ Both the mortality rate and costs associated with hospitalization are higher for older patients who develop surgical site infections compared with patients aged < 65 years, underscoring the importance of vigilant monitoring, early detection, and effective preoperative screening to identify and manage modifiable risk factors.⁴⁷ 

Postoperative delirium is another common complication of orthopedic surgery in the geriatric population, increasing morbidity and mortality. The incidence is reported to be as high as 53.3% in the trauma setting and 28.3% in the elective setting, indicating a need to assess patient risk preoperatively.^48,49 Several factors contribute to the high incidence of delirium, including advanced age, longer surgical durations, intraoperative hypotension and hypercapnia, pre-existing cognitive dysfunction, and postoperative sleep disorders.⁵⁰ 

VTE is another common cause of complications following orthopedic surgery. The development of DVT can lead to subsequent pulmonary embolism, which can be fatal. Orthopedic surgery patients are already at higher risk of DVT and VTE than other surgical patients, with an incidence as high as 40% to 60%, though it is frequently asymptomatic.^51,52 Geriatric patients may be more likely to have concurrent comorbidities that increase hypercoagulability.⁵³ Congestive heart failure, chronic kidney disease, and cardiovascular disease are all more common in older individuals and can increase the risk of VTE by 2-fold.⁵³ While anticoagulation is the standard of care to prevent VTE after orthopedic surgery, geriatric patients require more careful monitoring due to the higher incidence of bleeding complications. Additionally, early postoperative mobilization is critical to reduce the risk of DVT without significantly increasing pain or causing other adverse events.⁵⁴ 

Respiratory complications are common after orthopedic surgery, particularly atelectasis and bronchospasm, which can result from intraoperative mechanical ventilation.⁵⁵ While these conditions are typically self-limiting, more severe respiratory issues such as pneumonia are a significant concern because they may lead to the need for mechanical ventilation and admission to the intensive care unit (ICU). The more severe complications have an incidence of about 1% to 2% in orthopedic surgery patients.⁵⁶ Preventive strategies, such as respiratory physiotherapy and guided breathing exercises, are crucial to minimize perioperative pulmonary complications and promote optimal recovery. Addressing these challenges through early intervention is essential to improve outcomes.

Multidisciplinary Perioperative Care

Multidisciplinary care in orthopedic surgery involves collaborative management of patient care by general practitioners, surgeons, anesthesiologists, dietitians, physical and occupational therapists, inpatient health care practitioners (HCPs), and social services. The goal of this form of care is to provide a longitudinal sequence of health-optimization tactics that prepare a patient for surgery and give them the best chance of postoperative recovery.

Given that many aspects of geriatric health play a role in orthopedic postoperative outcomes, there are many preoperative factors to consider. As previously discussed, preoperative evaluation of geriatric patients should include nutritional and fragility screening to determine surgical candidacy and target modifiable risk factors for risk reduction. This screening can be conducted by primary care practitioners and orthopedic surgeons in an outpatient setting. A multidisciplinary approach benefits patients by decreasing time to surgery.³⁵ 

Several large studies have demonstrated the positive influence of a multidisciplinary approach on patient-oriented outcomes in orthopedic patients. Incorporation of this style of care in contrast to surgeon-led perioperative optimization leads to fewer floor and ICU admissions, shorter lengths of stay, and decreased mortality rates.^35,57 These findings are broadly applicable to a wide range of orthopedic surgeries and even surgeries outside of the musculoskeletal system.^58,59 In addition, this strategy has demonstrated reduced in-hospital health care costs due to shorter lengths of stay and fewer ICU admissions. Physical and occupational therapy also have irreplaceable roles in outcomes after orthopedic surgeries. They have independently been shown to decrease pain, increase range of motion, and increase functionality in daily life.⁶⁰ These aspects of recovery are essential for geriatric well-being.

Screening Tools

The World Health Organization FRAX fracture risk assessment tool (www.fraxplus.org/calculation-tool) was developed to identify patients at high risk of fracture and subsequent complications and to guide clinical decision-making regarding pharmacologic interventions.⁶¹ FRAX calculates the 10-year probability of fracture based on demographic factors, such as age and body mass index, clinical measures (eg, femoral neck bone mineral density), and risk factors (eg, prior fragility fractures, substance use history, and prolonged glucocorticoid use).⁶¹ The online tool is easy to use, making it a valuable resource for assessing fracture risk and determining appropriate treatment strategies.

The fatigue, resistance, ambulation, illnesses, loss of weight (FRAIL) scale assesses frailty in older adults. The scale classifies patients into 3 categories: robust, prefrail, and frail. The frail category is associated with an increased frequency of hip fracture and an elevated ASA class.⁶² Additionally, the FRAIL scale has demonstrated value in predicting hospital length of stay and the risk of postoperative complications.⁶² It also has shown utility in quantifying frailty status, which is traditionally challenging to assess systematically.⁶³

The Mini-Cog is commonly used in geriatric populations to screen for cognitive impairment. Preoperative Mini-Cog screening has been shown to predict the development of postoperative complications.⁶⁴ Geriatric patients who screened positive for cognitive impairment prior to orthopedic surgery were more likely to develop postoperative delirium, require alternative discharge disposition, and have a longer hospital length of stay.⁶⁴ Mini-Cog serves as an important preoperative tool for identifying patients who may benefit from closer postoperative monitoring and tailored care.

The Comprehensive Geriatric Assessment (CGA) is a multidimensional evaluation that has been validated for use in geriatric patients undergoing orthopedic surgery.⁶⁵ The CGA assesses functional status and the ability to perform activities of daily living (ADLs), such as eating, dressing, and ambulating. Poor ADLs are associated with increased risk of falls and cardiopulmonary complications. The CGA allows HCPs to identify patients at higher risk of complications and tailor interventions that optimize functional recovery during the perioperative period.

Nutritional screening is another component of preoperative evaluation in older adults undergoing orthopedic surgery. The Perioperative Nutrition Screen is a preoperative phone assessment of unintentional weight loss in the past 6 months.⁶⁶ Patients who screen positive are asked to come in for a preoperative visit with a registered dietitian who can further evaluate the nutritional status of the patient. 

The Mini Nutritional Assessment Short Form (MNA-SF), Malnutrition Universal Screening Tool, and Nutrition Risk Screening 2002 have all been validated for use in older patients undergoing orthopedic surgery. Among these, the MNA-SF has demonstrated superior utility in predicting hospital readmission and mortality.⁶⁷ Given the established links between malnutrition and poor surgical outcomes, routine nutritional screening is important for identifying geriatric patients who may require preoperative nutritional interventions.

CONCLUSIONS AND RECOMMENDATIONS

Perioperative management of geriatric patients undergoing orthopedic surgery requires an assessment and strategy focused on risk stratification, patient optimization, and mitigation of potential complications and mortality. Due to the complexity and comprehensive nature of an optimal perioperative plan, creating the plan early is essential to ensure adequate time for patient optimization and care coordination.

Nutrition plays a critical role in the success of surgical procedures, and orthopedics is no exception. Extra care should be taken to preoperatively optimize patient bone health before surgical intervention to enhance recovery and reduce the risk of complications. After an appropriate patient history and clinical picture are gathered, screening tools should be used on a case-by-case basis to further characterize comorbid conditions that may contribute to suboptimal outcomes. Additionally, given the proven association between frailty and fracture risk, frailty serves as a readily quantifiable predictor of patient-oriented outcomes. This should be assessed preoperatively with appropriate risk-stratification tools to determine appropriate postoperative measures to prevent morbidity and mortality. 

Orthopedic surgery is increasingly common in geriatric patients, who face higher perioperative risks due to age-related physiological changes, multimorbidity, and frailty. Optimizing preoperative assessment and adopting a multidisciplinary approach—integrating surgeons, anesthesiologists, physical therapists, and dietitians—can improve outcomes, reduce complications, and enhance recovery. The successful use of the tools and strategies outlined in this article by primary care should facilitate access to and recovery from orthopedic surgery in the geriatric population.

Lichen planus (LP) is a chronic inflammatory condition affecting the skin (cutaneous LP), mucous membranes (oral, ocular, or vulvar LP), hair (lichen planopilaris [LPP]), and nails that predominantly occurs in middle-aged adults. Although the true etiology remains unknown, the pathogenesis of LP is thought to involve multiple factors. Several human leukocyte antigen (HLA) alleles have been associated with LP and its variants, including HLA-B27, HLA-B51, HLA-DR1 (cutaneous and oral LP), HLA-DRB1*11, and HLA-DQB1*03 (LPP). Additionally, HLA-Bw57 has been reported to be associated with oral LP in a cohort of British patients.¹ In addition to HLA alleles, genetic polymorphisms in cytokines including IL-4, IL-6, IL-18, interferon (IFN) γ, and tumor necrosis factor (TNF) α and its receptor have been found to be associated with LP.² Beyond genetics, chronic viral infection has been implicated in the development of LP. Systemic infection with the hepatitis C virus has been linked to the development of oral LP by promoting the recruitment of hepatitis C virus–specific CD8+ T cells from peripheral blood to the oral lesions, where they exhibit a terminally differentiated effector status.³ Another report found an association between human herpesvirus 7 (HHV-7) and cutaneous LP; in this study, HHV-7 RNA was detected in plasmacytoid dendritic cells but not T cells and diminished after treatment, providing evidence for dendritic cells being involved in the HHV-7–mediated pathogenesis of cutaneous LP.⁴ These findings were further corroborated by another study of oral LP patients that found enhanced infiltration of plasmacytoid and myeloid dendritic cells and upregulation in toll-like receptor and IFN-γ signaling.⁴

In addition to immune cell dysregulation, LP and its variants have been linked to neurogenic inflammation. In oral LP lesions, neurokinin 1 receptor and substance P were highly expressed and demonstrated a positive correlation with the expression of apoptotic marker caspase-3 and proliferation marker Ki-67.⁵ These results suggest that neuropeptides may be involved in cell proliferation and turnover in oral LP. Similarly, in patients with LPP, substance P was more abundant in affected areas, whereas another neuropeptide, calcitonin gene-related peptide, was more highly expressed in unaffected areas,⁶ further supporting the pathogenic role of neurogenic inflammation in LP.

A mucosal variant that often goes undiagnosed is vulvar LP. Although no distinct pathologic mechanism for vulvar LP has been established, prior reports found an association with autoantibodies.^7,8 In patients with erosive vulvar LP, epidermal-binding basement membrane zone antibodies were detected in epidermal skin biopsies and in circulation with reactivity to bullous pemphigoid antigens 180 (9/11 [81.8%] patients) and 230 (2/11 [18.2%] patients).⁷ A similar study in patients with vulvar lichen sclerosus found similar proportions of circulating antibodies reactive to bullous pemphigoid antigens 180 (6/7 [85.7%] patients) and 230 (1/7 [14.3%] patients).⁸ Erosive vulvar LP has been shown to be associated with autoimmune disease (eg, alopecia areata, celiac disease and pernicious anemia),⁹ which suggests that the previously reported autoreactive antibodies^7,8 are secondary to autoimmunity rather than primary drivers of vulvar LP pathogenesis.

Certain medications also have been reported to cause cutaneous lichenoid drug eruptions. Although they can clinically and histologically mimic classic LP, lichenoid drug eruptions are a distinct entity. Common inciting medications include thiazide diuretics, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, antimalarials, checkpoint inhibitors, antimicrobials, antihypertensives, antidiabetics, and psychiatric drugs. The exact pathologic mechanism of lichenoid drug eruptions currently is unclear but is thought to involve the binding of drug molecules to the cell-surface proteins of the epidermis, creating an antigenic hapten stimulus for CD8+T cells and triggering apoptosis of keratinocytes.¹

The clinical severity of LP can range from mild localized disease to widespread and debilitating involvement. Multiple treatment modalities have been developed for management of LP, including topical and intralesional corticosteroids, phototherapy, Janus kinase inhibitors, phosphodiesterase-4 inhibitors, and anti–TNF-α inhibitors. Herein, we provide a narrative review and summary of the use of the TNF-α inhibitor adalimumab as a potential effective treatment for patients with LP.

Methods

We conducted a PubMed search of articles indexed for MEDLINE from 2005 to 2025 using the terms adalimumab AND lichen planus or adalimumab AND lichen. Articles that reported cases of oral LP, cutaneous LP, LPP, or lichenoid eruptions and adalimumab therapy were included in our review. Articles that used non-adalimumab TNF-α inhibitors were excluded. Using the search terms, 2 independent reviewers (M.G. and N.E.) conducted the literature review then screened the articles based on the inclusion and exclusion criteria. Our literature search yielded 40 articles, of which 20 met the criteria for inclusion in our narrative review.

Results

Our literature search yielded 11 patients with LP who were treated with adalimumab across studies (Table 1).^10-16 Prior LP treatments included topical corticosteroids (11/11 [100%]), disease-modifying antirheumatic drugs (6/11 [54.5%]), retinoids (4/11 [36.4%]), and psoralen plus UVA (1/11 [36.4%]). Adalimumab was administered subcutaneously following 4 treatment regimens: (1) 160 mg in week 1, then 80 mg in week 2, then 40 mg weekly for a median duration of 36 weeks (6/11 [54.5%]); (2) 80 mg in week 1, then 40 mg in week 2, 40 mg every 2 weeks for 20 weeks (1/11 [9.1%]); (3) 80 mg in week 1, then 40 mg every 2 weeks for a median duration of 12 weeks (2/11 [18.2%]); and (4) 40 mg every 2 weeks (2/11 [18.2%]). Adalimumab generally was well tolerated, with only 1 (9.1%) patient experiencing minor stress-related mucocutaneous flares on the tongue and extremities that resolved spontaneously.¹² Remission was achieved in 5 (45.5%) patients, with time to remission ranging from 2 to 4 months after adalimumab therapy, with a median of 2.5 months. In 1 (9.1%) patient with bullous LP, adalimumab therapy led to remission after 10 weeks. In both cases of oral and cutaneous LP (2/11 [18.2%]), remission was achieved after 2 months of treatment. Of the 2 LPP patients reported, 1 had hair regrowth after 9 months, and the other experienced remission after 3 months of adalimumab therapy. In the 1 (9.1%) case of annular LP, adalimumab treatment led to remission after 4 months. Five (45.5%) patients with vulvar LP treated with adalimumab for at least 9 months demonstrated improved Vulvar Quality of Life Index scores without improvement in their mucosal LP lesions. In 4 of the 5 (80.0%) patients who experienced remission after adalimumab treatment, remission lasted at least 6 to 10 months, with a median of 6 months; remission duration was not reported in 1 (20.0%) patient.

Paradoxically, our review of the literature yielded 12 patients in whom adalimumab was associated with lichenoid-type eruptions across 9 studies (Table 2).^17-29 The conditions for which these patients were undergoing treatment with adalimumab included ulcerative colitis,¹⁷ psoriasis,^18,19 Crohn disease,^20,26 rheumatoid arthritis,^21-23,26 oligoarthritis,²⁴ and ankylosing spondylitis.²⁵ Lichenoid drug eruptions occurred on the legs (5/12 [41.7%]), arms (3/12 [25%]), oral mucosa (2/12 [16.7%]), and forehead or scalp (2/12 [16.7%]). Onset of time to these lichenoid eruptions ranged from 2 weeks to 17 months, with a median of 4 months. Adalimumab was discontinued in 9 (75.0%) patients and was continued in 3 (25.0%). One patient who had an onset of their lichenoid eruption after 17 months of treatment with adalimumab continued to receive adalimumab therapy with the addition of topical corticosteroids, which led to resolution of their oral lesions and partial remission of their cutaneous lesions. In 1 (8.3%) patient with localized buccal lichenoid eruptions, discontinuation of adalimumab on its own was sufficient to completely clear the lesions. Seven patients (7/12 [58.3%]) received topical corticosteroids with minimal (2/12 [16.7%]) or moderate (4/12 [33.3%]) improvement, and 1 (8.3%) patient did not have reported outcomes data. Eosinophils were detected within the adalimumab-associated lichenoid eruptions in 3 (25.0%) patients.^17,20,22

In addition to its association with lichenoid drug eruptions, adalimumab also was reported to induce LPP in a patient who was being treated for Behçet disease,²⁹ oral LP in a patient being treated for Crohn disease,²⁷ and cutaneous LP in a patient being treated for Crohn disease (Table 2).²⁸ Time to onset ranged from 4 to 10 months, with a median of 6 months. Adalimumab was discontinued in 2 of 3 (66.7%) patients and was continued in the other patient (33.3%). After cessation of adalimumab therapy, administration of topical steroids led to complete resolution in the case of associated oral LP. In contrast, in adalimumab-induced cutaneous LP, initial topical corticosteroid treatment led to progression of lesions, which mostly resolved after adalimumab cessation. In 1 patient with LPP in whom adalimumab therapy could not be discontinued, topical corticosteroid and methotrexate therapy reduced the perifollicular erythema and stabilized the alopecia without full remission.

Comment

Conventional treatment modalities for LP often include topical corticosteroids as first-line therapy, with systemic corticosteroids, phototherapy, retinoids, or immunosuppressants (eg, cyclosporine or methotrexate) reserved for more severe or widespread disease. Historically, these approaches primarily have aimed to control symptoms rather than achieve long-term resolution; however, novel therapies including biologics and targeted immunomodulators show potential to induce sustained remission and improve quality of life for patients with refractory or mucosal LP.

In all reports where adalimumab was used to treat LP, patients initially received topical corticosteroids. While corticosteroids and other immunosuppressive agents are standard therapies, they often provide only temporary relief and may have an unfavorable side effect profile. Our review highlights the emerging role of adalimumab, a TNF-α inhibitor, in off-label management of LP subtypes, including cutaneous, mucosal, and vulvar LP and LPP. In several small case series and reports, patients treated with adalimumab experienced clinical improvement, including symptom resolution and quality-of-life enhancement, as well as complete remission, indicating a durable response.

The potential benefit of adalimumab in treating LP must be balanced with its paradoxical risk for inducing lichenoid eruptions as well as LP and its variants, as identified in our narrative review that included reports of patients receiving this biologic for other indications.^17-29 Since adalimumab is a fully humanized antibody, the development of neutralizing antibodies may not account for drug-induced LP and lichenoid eruptions. Given that it blocks TNF-α, adalimumab may induce these lesions through a cytokine imbalance. This is supported by data demonstrating enhanced type I IFN-related proteins in plaques of patients with psoriasiform lesions treated with TNF-α inhibitors.²⁶ These drug-induced eruptions often resolved or improved with topical corticosteroids after discontinuation, but their occurrence underscores the complexity of therapeutically targeting TNF-α in the management of LP. Our literature review suggests that adalimumab may offer therapeutic benefit in select cases of LP refractory to conventional therapy, especially when systemic control is required. Nonetheless, the risk for LP and lichenoid reactions necessitates cautious use and further investigation.

Conclusion

While the current evidence is limited to case reports and series, adalimumab shows promise as an effective and tolerable off-label treatment for LP, particularly in patients who are unresponsive to conventional immunosuppressive therapies. Remission or clinically significant improvement was achieved in several cases; however, the potential for adalimumab to induce LP and lichenoid eruptions underscores the need for careful patient selection and monitoring. Further prospective studies and larger cohorts are warranted to better define the safety and efficacy of adalimumab in treating LP lesions.

Lichen planus (LP) is a chronic inflammatory condition affecting the skin (cutaneous LP), mucous membranes (oral, ocular, or vulvar LP), hair (lichen planopilaris [LPP]), and nails that predominantly occurs in middle-aged adults. Although the true etiology remains unknown, the pathogenesis of LP is thought to involve multiple factors. Several human leukocyte antigen (HLA) alleles have been associated with LP and its variants, including HLA-B27, HLA-B51, HLA-DR1 (cutaneous and oral LP), HLA-DRB1*11, and HLA-DQB1*03 (LPP). Additionally, HLA-Bw57 has been reported to be associated with oral LP in a cohort of British patients.¹ In addition to HLA alleles, genetic polymorphisms in cytokines including IL-4, IL-6, IL-18, interferon (IFN) γ, and tumor necrosis factor (TNF) α and its receptor have been found to be associated with LP.² Beyond genetics, chronic viral infection has been implicated in the development of LP. Systemic infection with the hepatitis C virus has been linked to the development of oral LP by promoting the recruitment of hepatitis C virus–specific CD8+ T cells from peripheral blood to the oral lesions, where they exhibit a terminally differentiated effector status.³ Another report found an association between human herpesvirus 7 (HHV-7) and cutaneous LP; in this study, HHV-7 RNA was detected in plasmacytoid dendritic cells but not T cells and diminished after treatment, providing evidence for dendritic cells being involved in the HHV-7–mediated pathogenesis of cutaneous LP.⁴ These findings were further corroborated by another study of oral LP patients that found enhanced infiltration of plasmacytoid and myeloid dendritic cells and upregulation in toll-like receptor and IFN-γ signaling.⁴

In addition to immune cell dysregulation, LP and its variants have been linked to neurogenic inflammation. In oral LP lesions, neurokinin 1 receptor and substance P were highly expressed and demonstrated a positive correlation with the expression of apoptotic marker caspase-3 and proliferation marker Ki-67.⁵ These results suggest that neuropeptides may be involved in cell proliferation and turnover in oral LP. Similarly, in patients with LPP, substance P was more abundant in affected areas, whereas another neuropeptide, calcitonin gene-related peptide, was more highly expressed in unaffected areas,⁶ further supporting the pathogenic role of neurogenic inflammation in LP.

A mucosal variant that often goes undiagnosed is vulvar LP. Although no distinct pathologic mechanism for vulvar LP has been established, prior reports found an association with autoantibodies.^7,8 In patients with erosive vulvar LP, epidermal-binding basement membrane zone antibodies were detected in epidermal skin biopsies and in circulation with reactivity to bullous pemphigoid antigens 180 (9/11 [81.8%] patients) and 230 (2/11 [18.2%] patients).⁷ A similar study in patients with vulvar lichen sclerosus found similar proportions of circulating antibodies reactive to bullous pemphigoid antigens 180 (6/7 [85.7%] patients) and 230 (1/7 [14.3%] patients).⁸ Erosive vulvar LP has been shown to be associated with autoimmune disease (eg, alopecia areata, celiac disease and pernicious anemia),⁹ which suggests that the previously reported autoreactive antibodies^7,8 are secondary to autoimmunity rather than primary drivers of vulvar LP pathogenesis.

Certain medications also have been reported to cause cutaneous lichenoid drug eruptions. Although they can clinically and histologically mimic classic LP, lichenoid drug eruptions are a distinct entity. Common inciting medications include thiazide diuretics, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, antimalarials, checkpoint inhibitors, antimicrobials, antihypertensives, antidiabetics, and psychiatric drugs. The exact pathologic mechanism of lichenoid drug eruptions currently is unclear but is thought to involve the binding of drug molecules to the cell-surface proteins of the epidermis, creating an antigenic hapten stimulus for CD8+T cells and triggering apoptosis of keratinocytes.¹

The clinical severity of LP can range from mild localized disease to widespread and debilitating involvement. Multiple treatment modalities have been developed for management of LP, including topical and intralesional corticosteroids, phototherapy, Janus kinase inhibitors, phosphodiesterase-4 inhibitors, and anti–TNF-α inhibitors. Herein, we provide a narrative review and summary of the use of the TNF-α inhibitor adalimumab as a potential effective treatment for patients with LP.

Methods

We conducted a PubMed search of articles indexed for MEDLINE from 2005 to 2025 using the terms adalimumab AND lichen planus or adalimumab AND lichen. Articles that reported cases of oral LP, cutaneous LP, LPP, or lichenoid eruptions and adalimumab therapy were included in our review. Articles that used non-adalimumab TNF-α inhibitors were excluded. Using the search terms, 2 independent reviewers (M.G. and N.E.) conducted the literature review then screened the articles based on the inclusion and exclusion criteria. Our literature search yielded 40 articles, of which 20 met the criteria for inclusion in our narrative review.

Results

Our literature search yielded 11 patients with LP who were treated with adalimumab across studies (Table 1).^10-16 Prior LP treatments included topical corticosteroids (11/11 [100%]), disease-modifying antirheumatic drugs (6/11 [54.5%]), retinoids (4/11 [36.4%]), and psoralen plus UVA (1/11 [36.4%]). Adalimumab was administered subcutaneously following 4 treatment regimens: (1) 160 mg in week 1, then 80 mg in week 2, then 40 mg weekly for a median duration of 36 weeks (6/11 [54.5%]); (2) 80 mg in week 1, then 40 mg in week 2, 40 mg every 2 weeks for 20 weeks (1/11 [9.1%]); (3) 80 mg in week 1, then 40 mg every 2 weeks for a median duration of 12 weeks (2/11 [18.2%]); and (4) 40 mg every 2 weeks (2/11 [18.2%]). Adalimumab generally was well tolerated, with only 1 (9.1%) patient experiencing minor stress-related mucocutaneous flares on the tongue and extremities that resolved spontaneously.¹² Remission was achieved in 5 (45.5%) patients, with time to remission ranging from 2 to 4 months after adalimumab therapy, with a median of 2.5 months. In 1 (9.1%) patient with bullous LP, adalimumab therapy led to remission after 10 weeks. In both cases of oral and cutaneous LP (2/11 [18.2%]), remission was achieved after 2 months of treatment. Of the 2 LPP patients reported, 1 had hair regrowth after 9 months, and the other experienced remission after 3 months of adalimumab therapy. In the 1 (9.1%) case of annular LP, adalimumab treatment led to remission after 4 months. Five (45.5%) patients with vulvar LP treated with adalimumab for at least 9 months demonstrated improved Vulvar Quality of Life Index scores without improvement in their mucosal LP lesions. In 4 of the 5 (80.0%) patients who experienced remission after adalimumab treatment, remission lasted at least 6 to 10 months, with a median of 6 months; remission duration was not reported in 1 (20.0%) patient.

Paradoxically, our review of the literature yielded 12 patients in whom adalimumab was associated with lichenoid-type eruptions across 9 studies (Table 2).^17-29 The conditions for which these patients were undergoing treatment with adalimumab included ulcerative colitis,¹⁷ psoriasis,^18,19 Crohn disease,^20,26 rheumatoid arthritis,^21-23,26 oligoarthritis,²⁴ and ankylosing spondylitis.²⁵ Lichenoid drug eruptions occurred on the legs (5/12 [41.7%]), arms (3/12 [25%]), oral mucosa (2/12 [16.7%]), and forehead or scalp (2/12 [16.7%]). Onset of time to these lichenoid eruptions ranged from 2 weeks to 17 months, with a median of 4 months. Adalimumab was discontinued in 9 (75.0%) patients and was continued in 3 (25.0%). One patient who had an onset of their lichenoid eruption after 17 months of treatment with adalimumab continued to receive adalimumab therapy with the addition of topical corticosteroids, which led to resolution of their oral lesions and partial remission of their cutaneous lesions. In 1 (8.3%) patient with localized buccal lichenoid eruptions, discontinuation of adalimumab on its own was sufficient to completely clear the lesions. Seven patients (7/12 [58.3%]) received topical corticosteroids with minimal (2/12 [16.7%]) or moderate (4/12 [33.3%]) improvement, and 1 (8.3%) patient did not have reported outcomes data. Eosinophils were detected within the adalimumab-associated lichenoid eruptions in 3 (25.0%) patients.^17,20,22

In addition to its association with lichenoid drug eruptions, adalimumab also was reported to induce LPP in a patient who was being treated for Behçet disease,²⁹ oral LP in a patient being treated for Crohn disease,²⁷ and cutaneous LP in a patient being treated for Crohn disease (Table 2).²⁸ Time to onset ranged from 4 to 10 months, with a median of 6 months. Adalimumab was discontinued in 2 of 3 (66.7%) patients and was continued in the other patient (33.3%). After cessation of adalimumab therapy, administration of topical steroids led to complete resolution in the case of associated oral LP. In contrast, in adalimumab-induced cutaneous LP, initial topical corticosteroid treatment led to progression of lesions, which mostly resolved after adalimumab cessation. In 1 patient with LPP in whom adalimumab therapy could not be discontinued, topical corticosteroid and methotrexate therapy reduced the perifollicular erythema and stabilized the alopecia without full remission.

Comment

Conventional treatment modalities for LP often include topical corticosteroids as first-line therapy, with systemic corticosteroids, phototherapy, retinoids, or immunosuppressants (eg, cyclosporine or methotrexate) reserved for more severe or widespread disease. Historically, these approaches primarily have aimed to control symptoms rather than achieve long-term resolution; however, novel therapies including biologics and targeted immunomodulators show potential to induce sustained remission and improve quality of life for patients with refractory or mucosal LP.

In all reports where adalimumab was used to treat LP, patients initially received topical corticosteroids. While corticosteroids and other immunosuppressive agents are standard therapies, they often provide only temporary relief and may have an unfavorable side effect profile. Our review highlights the emerging role of adalimumab, a TNF-α inhibitor, in off-label management of LP subtypes, including cutaneous, mucosal, and vulvar LP and LPP. In several small case series and reports, patients treated with adalimumab experienced clinical improvement, including symptom resolution and quality-of-life enhancement, as well as complete remission, indicating a durable response.

The potential benefit of adalimumab in treating LP must be balanced with its paradoxical risk for inducing lichenoid eruptions as well as LP and its variants, as identified in our narrative review that included reports of patients receiving this biologic for other indications.^17-29 Since adalimumab is a fully humanized antibody, the development of neutralizing antibodies may not account for drug-induced LP and lichenoid eruptions. Given that it blocks TNF-α, adalimumab may induce these lesions through a cytokine imbalance. This is supported by data demonstrating enhanced type I IFN-related proteins in plaques of patients with psoriasiform lesions treated with TNF-α inhibitors.²⁶ These drug-induced eruptions often resolved or improved with topical corticosteroids after discontinuation, but their occurrence underscores the complexity of therapeutically targeting TNF-α in the management of LP. Our literature review suggests that adalimumab may offer therapeutic benefit in select cases of LP refractory to conventional therapy, especially when systemic control is required. Nonetheless, the risk for LP and lichenoid reactions necessitates cautious use and further investigation.

Conclusion

While the current evidence is limited to case reports and series, adalimumab shows promise as an effective and tolerable off-label treatment for LP, particularly in patients who are unresponsive to conventional immunosuppressive therapies. Remission or clinically significant improvement was achieved in several cases; however, the potential for adalimumab to induce LP and lichenoid eruptions underscores the need for careful patient selection and monitoring. Further prospective studies and larger cohorts are warranted to better define the safety and efficacy of adalimumab in treating LP lesions.

Lichen planus (LP) is a chronic inflammatory condition affecting the skin (cutaneous LP), mucous membranes (oral, ocular, or vulvar LP), hair (lichen planopilaris [LPP]), and nails that predominantly occurs in middle-aged adults. Although the true etiology remains unknown, the pathogenesis of LP is thought to involve multiple factors. Several human leukocyte antigen (HLA) alleles have been associated with LP and its variants, including HLA-B27, HLA-B51, HLA-DR1 (cutaneous and oral LP), HLA-DRB1*11, and HLA-DQB1*03 (LPP). Additionally, HLA-Bw57 has been reported to be associated with oral LP in a cohort of British patients.¹ In addition to HLA alleles, genetic polymorphisms in cytokines including IL-4, IL-6, IL-18, interferon (IFN) γ, and tumor necrosis factor (TNF) α and its receptor have been found to be associated with LP.² Beyond genetics, chronic viral infection has been implicated in the development of LP. Systemic infection with the hepatitis C virus has been linked to the development of oral LP by promoting the recruitment of hepatitis C virus–specific CD8+ T cells from peripheral blood to the oral lesions, where they exhibit a terminally differentiated effector status.³ Another report found an association between human herpesvirus 7 (HHV-7) and cutaneous LP; in this study, HHV-7 RNA was detected in plasmacytoid dendritic cells but not T cells and diminished after treatment, providing evidence for dendritic cells being involved in the HHV-7–mediated pathogenesis of cutaneous LP.⁴ These findings were further corroborated by another study of oral LP patients that found enhanced infiltration of plasmacytoid and myeloid dendritic cells and upregulation in toll-like receptor and IFN-γ signaling.⁴

In addition to immune cell dysregulation, LP and its variants have been linked to neurogenic inflammation. In oral LP lesions, neurokinin 1 receptor and substance P were highly expressed and demonstrated a positive correlation with the expression of apoptotic marker caspase-3 and proliferation marker Ki-67.⁵ These results suggest that neuropeptides may be involved in cell proliferation and turnover in oral LP. Similarly, in patients with LPP, substance P was more abundant in affected areas, whereas another neuropeptide, calcitonin gene-related peptide, was more highly expressed in unaffected areas,⁶ further supporting the pathogenic role of neurogenic inflammation in LP.

A mucosal variant that often goes undiagnosed is vulvar LP. Although no distinct pathologic mechanism for vulvar LP has been established, prior reports found an association with autoantibodies.^7,8 In patients with erosive vulvar LP, epidermal-binding basement membrane zone antibodies were detected in epidermal skin biopsies and in circulation with reactivity to bullous pemphigoid antigens 180 (9/11 [81.8%] patients) and 230 (2/11 [18.2%] patients).⁷ A similar study in patients with vulvar lichen sclerosus found similar proportions of circulating antibodies reactive to bullous pemphigoid antigens 180 (6/7 [85.7%] patients) and 230 (1/7 [14.3%] patients).⁸ Erosive vulvar LP has been shown to be associated with autoimmune disease (eg, alopecia areata, celiac disease and pernicious anemia),⁹ which suggests that the previously reported autoreactive antibodies^7,8 are secondary to autoimmunity rather than primary drivers of vulvar LP pathogenesis.

Certain medications also have been reported to cause cutaneous lichenoid drug eruptions. Although they can clinically and histologically mimic classic LP, lichenoid drug eruptions are a distinct entity. Common inciting medications include thiazide diuretics, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, antimalarials, checkpoint inhibitors, antimicrobials, antihypertensives, antidiabetics, and psychiatric drugs. The exact pathologic mechanism of lichenoid drug eruptions currently is unclear but is thought to involve the binding of drug molecules to the cell-surface proteins of the epidermis, creating an antigenic hapten stimulus for CD8+T cells and triggering apoptosis of keratinocytes.¹

The clinical severity of LP can range from mild localized disease to widespread and debilitating involvement. Multiple treatment modalities have been developed for management of LP, including topical and intralesional corticosteroids, phototherapy, Janus kinase inhibitors, phosphodiesterase-4 inhibitors, and anti–TNF-α inhibitors. Herein, we provide a narrative review and summary of the use of the TNF-α inhibitor adalimumab as a potential effective treatment for patients with LP.

Methods

We conducted a PubMed search of articles indexed for MEDLINE from 2005 to 2025 using the terms adalimumab AND lichen planus or adalimumab AND lichen. Articles that reported cases of oral LP, cutaneous LP, LPP, or lichenoid eruptions and adalimumab therapy were included in our review. Articles that used non-adalimumab TNF-α inhibitors were excluded. Using the search terms, 2 independent reviewers (M.G. and N.E.) conducted the literature review then screened the articles based on the inclusion and exclusion criteria. Our literature search yielded 40 articles, of which 20 met the criteria for inclusion in our narrative review.

Results

Our literature search yielded 11 patients with LP who were treated with adalimumab across studies (Table 1).^10-16 Prior LP treatments included topical corticosteroids (11/11 [100%]), disease-modifying antirheumatic drugs (6/11 [54.5%]), retinoids (4/11 [36.4%]), and psoralen plus UVA (1/11 [36.4%]). Adalimumab was administered subcutaneously following 4 treatment regimens: (1) 160 mg in week 1, then 80 mg in week 2, then 40 mg weekly for a median duration of 36 weeks (6/11 [54.5%]); (2) 80 mg in week 1, then 40 mg in week 2, 40 mg every 2 weeks for 20 weeks (1/11 [9.1%]); (3) 80 mg in week 1, then 40 mg every 2 weeks for a median duration of 12 weeks (2/11 [18.2%]); and (4) 40 mg every 2 weeks (2/11 [18.2%]). Adalimumab generally was well tolerated, with only 1 (9.1%) patient experiencing minor stress-related mucocutaneous flares on the tongue and extremities that resolved spontaneously.¹² Remission was achieved in 5 (45.5%) patients, with time to remission ranging from 2 to 4 months after adalimumab therapy, with a median of 2.5 months. In 1 (9.1%) patient with bullous LP, adalimumab therapy led to remission after 10 weeks. In both cases of oral and cutaneous LP (2/11 [18.2%]), remission was achieved after 2 months of treatment. Of the 2 LPP patients reported, 1 had hair regrowth after 9 months, and the other experienced remission after 3 months of adalimumab therapy. In the 1 (9.1%) case of annular LP, adalimumab treatment led to remission after 4 months. Five (45.5%) patients with vulvar LP treated with adalimumab for at least 9 months demonstrated improved Vulvar Quality of Life Index scores without improvement in their mucosal LP lesions. In 4 of the 5 (80.0%) patients who experienced remission after adalimumab treatment, remission lasted at least 6 to 10 months, with a median of 6 months; remission duration was not reported in 1 (20.0%) patient.

Paradoxically, our review of the literature yielded 12 patients in whom adalimumab was associated with lichenoid-type eruptions across 9 studies (Table 2).^17-29 The conditions for which these patients were undergoing treatment with adalimumab included ulcerative colitis,¹⁷ psoriasis,^18,19 Crohn disease,^20,26 rheumatoid arthritis,^21-23,26 oligoarthritis,²⁴ and ankylosing spondylitis.²⁵ Lichenoid drug eruptions occurred on the legs (5/12 [41.7%]), arms (3/12 [25%]), oral mucosa (2/12 [16.7%]), and forehead or scalp (2/12 [16.7%]). Onset of time to these lichenoid eruptions ranged from 2 weeks to 17 months, with a median of 4 months. Adalimumab was discontinued in 9 (75.0%) patients and was continued in 3 (25.0%). One patient who had an onset of their lichenoid eruption after 17 months of treatment with adalimumab continued to receive adalimumab therapy with the addition of topical corticosteroids, which led to resolution of their oral lesions and partial remission of their cutaneous lesions. In 1 (8.3%) patient with localized buccal lichenoid eruptions, discontinuation of adalimumab on its own was sufficient to completely clear the lesions. Seven patients (7/12 [58.3%]) received topical corticosteroids with minimal (2/12 [16.7%]) or moderate (4/12 [33.3%]) improvement, and 1 (8.3%) patient did not have reported outcomes data. Eosinophils were detected within the adalimumab-associated lichenoid eruptions in 3 (25.0%) patients.^17,20,22

In addition to its association with lichenoid drug eruptions, adalimumab also was reported to induce LPP in a patient who was being treated for Behçet disease,²⁹ oral LP in a patient being treated for Crohn disease,²⁷ and cutaneous LP in a patient being treated for Crohn disease (Table 2).²⁸ Time to onset ranged from 4 to 10 months, with a median of 6 months. Adalimumab was discontinued in 2 of 3 (66.7%) patients and was continued in the other patient (33.3%). After cessation of adalimumab therapy, administration of topical steroids led to complete resolution in the case of associated oral LP. In contrast, in adalimumab-induced cutaneous LP, initial topical corticosteroid treatment led to progression of lesions, which mostly resolved after adalimumab cessation. In 1 patient with LPP in whom adalimumab therapy could not be discontinued, topical corticosteroid and methotrexate therapy reduced the perifollicular erythema and stabilized the alopecia without full remission.

Comment

Conventional treatment modalities for LP often include topical corticosteroids as first-line therapy, with systemic corticosteroids, phototherapy, retinoids, or immunosuppressants (eg, cyclosporine or methotrexate) reserved for more severe or widespread disease. Historically, these approaches primarily have aimed to control symptoms rather than achieve long-term resolution; however, novel therapies including biologics and targeted immunomodulators show potential to induce sustained remission and improve quality of life for patients with refractory or mucosal LP.

In all reports where adalimumab was used to treat LP, patients initially received topical corticosteroids. While corticosteroids and other immunosuppressive agents are standard therapies, they often provide only temporary relief and may have an unfavorable side effect profile. Our review highlights the emerging role of adalimumab, a TNF-α inhibitor, in off-label management of LP subtypes, including cutaneous, mucosal, and vulvar LP and LPP. In several small case series and reports, patients treated with adalimumab experienced clinical improvement, including symptom resolution and quality-of-life enhancement, as well as complete remission, indicating a durable response.

The potential benefit of adalimumab in treating LP must be balanced with its paradoxical risk for inducing lichenoid eruptions as well as LP and its variants, as identified in our narrative review that included reports of patients receiving this biologic for other indications.^17-29 Since adalimumab is a fully humanized antibody, the development of neutralizing antibodies may not account for drug-induced LP and lichenoid eruptions. Given that it blocks TNF-α, adalimumab may induce these lesions through a cytokine imbalance. This is supported by data demonstrating enhanced type I IFN-related proteins in plaques of patients with psoriasiform lesions treated with TNF-α inhibitors.²⁶ These drug-induced eruptions often resolved or improved with topical corticosteroids after discontinuation, but their occurrence underscores the complexity of therapeutically targeting TNF-α in the management of LP. Our literature review suggests that adalimumab may offer therapeutic benefit in select cases of LP refractory to conventional therapy, especially when systemic control is required. Nonetheless, the risk for LP and lichenoid reactions necessitates cautious use and further investigation.

Conclusion

While the current evidence is limited to case reports and series, adalimumab shows promise as an effective and tolerable off-label treatment for LP, particularly in patients who are unresponsive to conventional immunosuppressive therapies. Remission or clinically significant improvement was achieved in several cases; however, the potential for adalimumab to induce LP and lichenoid eruptions underscores the need for careful patient selection and monitoring. Further prospective studies and larger cohorts are warranted to better define the safety and efficacy of adalimumab in treating LP lesions.

Psoriasis, a chronic immune-mediated skin disease, is increasingly recognized for its systemic inflammation and associated cardiometabolic risk. The global rise of obesity has revealed a critical link between these 2 conditions. Current evidence confirms that obesity is an independent risk factor that can trigger psoriasis onset, drive more severe disease, and substantially impair treatment efficacy.^1,2 This review synthesizes the latest evidence on the shared pathophysiology, clinical consequences, and integrated management strategies for patients with both psoriasis and obesity.

Pathophysiologic Links Between Psoriasis and Obesity

Emerging evidence highlights a bidirectional relationship between psoriasis and obesity rooted in overlapping inflammatory pathways. Both conditions are characterized by chronic inflammation mediated by cytokines that sustain systemic immune activation and metabolic dysfunction. This interplay creates a reciprocal process in which psoriatic inflammation promotes metabolic disturbances while obesity amplifies systemic inflammation and disease severity.³

Psoriasis may contribute to obesity through cytokine-driven metabolic alterations in insulin signaling and adipocyte function. The psoriatic immune response is dominated by T helper (Th) 1, Th17, and Th22 cell activation, leading to elevated levels of interferon-γ, tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-17, and IL-22 from keratinocytes.⁴ These cytokines contribute not only to cutaneous inflammation but also to insulin resistance and adipocyte dysfunction.⁵ Tumor necrosis factor α and IL-6 interfere with insulin signaling via activation of stress kinases (eg, IκB kinase and c-Jun N-terminal kinase), implicating these molecules in insulin resistance and weight gain.⁶ Moreover, IL-17, a central cytokine in psoriasis, has been implicated in vascular inflammation, insulin resistance, and type 2 diabetes, suggesting a mechanistic link between psoriatic inflammation and metabolic disease.⁵ Additionally, chronic systemic inflammation in psoriasis suppresses adiponectin, a protective adipokine that enhances insulin sensitivity and exerts anti-inflammatory effects by inhibiting TNF-α and IL-6 production while promoting IL-10 synthesis. Reduced adiponectin levels have consistently been observed in patients with psoriasis and concomitant obesity or metabolic syndrome.³ The resultant imbalance between proinflammatory and anti-inflammatory mediators creates a metabolic environment conducive to obesity.³

Conversely, obesity itself may intensify both the incidence and severity of psoriasis through shared inflammatory pathways. Leptin, whose expression rises proportionally with adipocyte mass, acts as a proinflammatory mediator linking obesity to psoriasis exacerbation. By promoting Th1 and Th17 cell differentiation and suppressing regulatory T-cell activity, leptin increases IL-17A, IL-6, and TNF-α production.⁷ These cytokines stimulate keratinocyte proliferation and perpetuate cutaneous inflammation, thereby intensifying disease activity. Similarly, resistin, another adipokine that is elevated in obesity, stimulates monocytes and macrophages to secrete TNF-α and IL-6, creating a proinflammatory state in the body that drives the relationship between excessive fat storage (adiposity) and the development and severity of psoriasis.⁸ In contrast, reduced adiponectin levels in obesity remove a key anti-inflammatory regulator that normally inhibits TNF-α and IL-6 synthesis and promotes IL-10 production. This deficiency provokes unrestrained cytokine activation within both adipose and cutaneous tissue, exacerbating psoriatic immune dysregulation.⁹

Free fatty acids derived from abundant adipocytes in obesity further activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–signaling and induce oxidative stress, augmenting systemic inflammation. Adipose tissue macrophages additionally secrete IL-1Β, IL-6, and TNF-α, which promote keratinocyte proliferation and amplify the psoriatic inflammatory cascade. Importantly, anti–TNF-α therapy has been shown to improve metabolic parameters, reducing low-density lipoprotein and total cholesterol levels and enhancing insulin sensitivity, highlighting the reciprocal benefits of dampening the inflammatory signaling from TNF-α.⁵

Together, these findings highlight that psoriasis and obesity are interconnected inflammatory disorders driven by overlapping cytokine networks, most notably TNF-α, IL-6, IL-17, and IL-23, and by imbalances in adipokines such as leptin, resistin, and adiponectin (Table).

Clinical Implications of Obesity-Related Comorbidities

Higher body mass index (BMI) has been associated with an increased and earlier incidence of psoriasis. When treated as continuous variables, both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index scores were positively correlated with increases in BMI.^10,11 This close association suggests BMI may function as a practical indicator of disease severity and prognosis.^7,8,11

Psoriatic arthritis (PsA) is a major comorbidity of psoriasis that impacts disease severity and quality of life. Obesity is associated with an increased risk for PsA after accounting for traditional risk factors. Psoriatic arthritis can cause chronic mobility issues and complicate a patient’s ability to stay active. Early rheumatologist involvement may be warranted to prevent PsA development in patients with obesity and psoriasis.^11,12

Patients with psoriasis have an increased baseline risk for metabolic syndrome, including obesity, type 2 diabetes, hypertension, and dyslipidemia^11,13,14; therefore, the presence of obesity warrants regular metabolic evaluation. Unmanaged metabolic syndrome contributes to the increased prevalence of myocardial infarction, stroke, and heart failure seen with psoriasis.^13,14 Obesity also may cause obstructive sleep apnea, which can exacerbate hypertension and heart disease due to chronic hypoxia.¹¹ The interplay of these metabolic factors puts patients with psoriasis and obesity at heightened cardiovascular risk.^13,14

Both psoriasis and obesity present psychosocial challenges such as elevated rates of depression, anxiety, and body-image concerns, all of which become more pronounced when these conditions coexist. These psychological stressors may hinder a patient’s motivation for lifestyle changes or treatment adherence.¹³

Dermatology visits serve as an important opportunity to monitor obesity-related comorbidities.^13,15 Dermatologists are uniquely positioned to initiate metabolic screening while collaborating with primary care physicians for ongoing cardiometabolic management. Metabolic and cardiovascular baselines should be measured when care is established and should be followed longitudinally—these include BMI, waist circumference measurements, blood pressure, lipid panels, fasting glucose or A1C levels, and liver enzymes.^10,14,15 Regular screening for depression, suicidality, and disordered eating also is encouraged.¹³ Clinicians should follow established guidelines to identify and manage metabolic, cardiovascular, and psychological comorbidities.¹³

Impact of Obesity on Psoriasis Treatment

Obesity is a critical factor in clinical decision-making, as it consistently is associated with diminished response to numerous systemic psoriasis therapies. This reduced efficacy has been observed with conventional oral agents such as methotrexate and cyclosporine and is particularly well documented in the context of biologic therapies.^15,16 Several meta-analyses and large real-world studies have shown that higher BMI is associated with a suboptimal treatment response, with patients in higher BMI categories achieving lower rates of PASI 75 and PASI 90 than their nonobese counterparts receiving the same regimen.^15,17

This efficacy gap often is rooted in pharmacokinetic challenges. For many biologics administered via subcutaneous injection, increased BMI can lead to altered drug distribution, such as sequestration in adipose tissue. Altered distribution combined with potentially increased drug clearance can result in lower overall serum drug concentrations and subsequent underdosing for a patient’s inflammatory burden.¹⁵ This reality highlights the important distinction between fixed and weight-based dosing strategies. Therapies dosed by weight, such as infliximab, have demonstrated more consistent efficacy in populations with obesity, as the dose is escalated to match patient size.¹⁸ Despite the weight-dependent effect, recent real-world studies have suggested that fixed dosing of some IL-17A inhibitors (eg, ixekizumab) remains highly effective across BMI categories, while others (eg, secukinumab) show diminished efficacy in obese patients.^16,19 Furthermore, some real-world studies have reported an inverse relationship between elevated BMI and efficacy of IL-23 inhibitors, particularly guselkumab, while other studies reported no association.^20,21 These mixed observations support a nuanced interpretation of BMI’s role in treatment modification; consideration should be given to the specific medication and the dosing strategy over biologic class alone.

Whether obesity independently drives psoriasis severity or mainly diminishes treatment efficacy through pharmacokinetic effects remains debated. Observational studies show a dose-dependent relationship between BMI and disease severity even in untreated patients, supporting a proinflammatory role for obesity.¹⁰ Concurrently, higher BMI may predict lower responses to some fixed-dose biologics, likely due to altered distribution and sequestration in adipose tissue.^15,20 The precise contributions are challenging to delineate; both likely converge to heighten disease severity and reduce treatment response.

Beyond efficacy, obesity compounds the safety considerations of systemic treatments. Psoriasis and obesity are both strong independent risk factors for metabolic ­dysfunction–associated steatotic liver disease. This prevalent comorbidity creates a substantial clinical dilemma, as a first-line, cost-effective agent such as methotrexate carries a known risk for hepatotoxicity, which is amplified in patients with pre-existing liver steatosis.¹³ Consequently, the presence of obesity and metabolic dysfunction–associated steatotic liver disease often limits the use of methotrexate, forcing a change in therapy. Thorough baseline comorbidity screening in all patients with psoriasis and obesity is necessary to select a therapy that balances efficacy with safety.^13,14

Management Strategies

Weight management plays a pivotal role in improving psoriasis outcomes. Even modest weight loss of 5% to 10% has been shown in randomized and observational studies to substantially reduce disease severity, reflected by lower PASI and Dermatology Life Quality Index scores and enhance treatment responsiveness.^22,23 Dietary approaches emphasizing hypocaloric, Mediterranean, or ­anti-inflammatory patterns have demonstrated additional improvements in disease activity, likely through attenuation of systemic inflammation and metabolic dysregulation.²¹ Bariatric surgery provides more sustained benefits, with multiple studies reporting long-term remission or reduced psoriasis severity following substantial postoperative weight loss.^23,24

Pharmacologic weight-loss therapies, particularly glucagonlike peptide-1 receptor agonists, have emerged as potential adjuncts in psoriasis management. Although data remain limited, these agents may reduce systemic inflammation, improve insulin sensitivity, and indirectly enhance biologic response.²⁵

Conclusion

Psoriasis and obesity are interconnected chronic inflammatory conditions that share overlapping cytokine pathways and mutually exacerbate the clinical course. Systemic inflammation driven by cytokines such as TNF-α, IL-6, and IL-17 not only promotes psoriatic skin disease but also contributes to metabolic dysfunction and cardiovascular risk. In turn, excess adiposity amplifies inflammatory signaling and diminishes therapeutic response, creating a self-perpetuating cycle of disease.

Dermatologists should identify obesity-related risks early; counsel patients on lifestyle changes; initiate metabolic screening; and coordinate care across primary care, nutrition, and rheumatology. Regular screening for metabolic syndrome, cardiovascular comorbidities, and psychosocial distress should be integrated into psoriasis management. Future research should focus on personalized treatment strategies that integrate management of inflammatory skin disease with underlying metabolic health, such as optimizing biologic dosing and identifying novel targets that disrupt the pathophysiologic loop. By recognizing and addressing the shared inflammatory mechanisms of psoriasis and obesity, clinicians can improve both dermatologic and systemic outcomes for affected patients.

Psoriasis, a chronic immune-mediated skin disease, is increasingly recognized for its systemic inflammation and associated cardiometabolic risk. The global rise of obesity has revealed a critical link between these 2 conditions. Current evidence confirms that obesity is an independent risk factor that can trigger psoriasis onset, drive more severe disease, and substantially impair treatment efficacy.^1,2 This review synthesizes the latest evidence on the shared pathophysiology, clinical consequences, and integrated management strategies for patients with both psoriasis and obesity.

Pathophysiologic Links Between Psoriasis and Obesity

Emerging evidence highlights a bidirectional relationship between psoriasis and obesity rooted in overlapping inflammatory pathways. Both conditions are characterized by chronic inflammation mediated by cytokines that sustain systemic immune activation and metabolic dysfunction. This interplay creates a reciprocal process in which psoriatic inflammation promotes metabolic disturbances while obesity amplifies systemic inflammation and disease severity.³

Psoriasis may contribute to obesity through cytokine-driven metabolic alterations in insulin signaling and adipocyte function. The psoriatic immune response is dominated by T helper (Th) 1, Th17, and Th22 cell activation, leading to elevated levels of interferon-γ, tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-17, and IL-22 from keratinocytes.⁴ These cytokines contribute not only to cutaneous inflammation but also to insulin resistance and adipocyte dysfunction.⁵ Tumor necrosis factor α and IL-6 interfere with insulin signaling via activation of stress kinases (eg, IκB kinase and c-Jun N-terminal kinase), implicating these molecules in insulin resistance and weight gain.⁶ Moreover, IL-17, a central cytokine in psoriasis, has been implicated in vascular inflammation, insulin resistance, and type 2 diabetes, suggesting a mechanistic link between psoriatic inflammation and metabolic disease.⁵ Additionally, chronic systemic inflammation in psoriasis suppresses adiponectin, a protective adipokine that enhances insulin sensitivity and exerts anti-inflammatory effects by inhibiting TNF-α and IL-6 production while promoting IL-10 synthesis. Reduced adiponectin levels have consistently been observed in patients with psoriasis and concomitant obesity or metabolic syndrome.³ The resultant imbalance between proinflammatory and anti-inflammatory mediators creates a metabolic environment conducive to obesity.³

Conversely, obesity itself may intensify both the incidence and severity of psoriasis through shared inflammatory pathways. Leptin, whose expression rises proportionally with adipocyte mass, acts as a proinflammatory mediator linking obesity to psoriasis exacerbation. By promoting Th1 and Th17 cell differentiation and suppressing regulatory T-cell activity, leptin increases IL-17A, IL-6, and TNF-α production.⁷ These cytokines stimulate keratinocyte proliferation and perpetuate cutaneous inflammation, thereby intensifying disease activity. Similarly, resistin, another adipokine that is elevated in obesity, stimulates monocytes and macrophages to secrete TNF-α and IL-6, creating a proinflammatory state in the body that drives the relationship between excessive fat storage (adiposity) and the development and severity of psoriasis.⁸ In contrast, reduced adiponectin levels in obesity remove a key anti-inflammatory regulator that normally inhibits TNF-α and IL-6 synthesis and promotes IL-10 production. This deficiency provokes unrestrained cytokine activation within both adipose and cutaneous tissue, exacerbating psoriatic immune dysregulation.⁹

Free fatty acids derived from abundant adipocytes in obesity further activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–signaling and induce oxidative stress, augmenting systemic inflammation. Adipose tissue macrophages additionally secrete IL-1Β, IL-6, and TNF-α, which promote keratinocyte proliferation and amplify the psoriatic inflammatory cascade. Importantly, anti–TNF-α therapy has been shown to improve metabolic parameters, reducing low-density lipoprotein and total cholesterol levels and enhancing insulin sensitivity, highlighting the reciprocal benefits of dampening the inflammatory signaling from TNF-α.⁵

Together, these findings highlight that psoriasis and obesity are interconnected inflammatory disorders driven by overlapping cytokine networks, most notably TNF-α, IL-6, IL-17, and IL-23, and by imbalances in adipokines such as leptin, resistin, and adiponectin (Table).

Clinical Implications of Obesity-Related Comorbidities

Higher body mass index (BMI) has been associated with an increased and earlier incidence of psoriasis. When treated as continuous variables, both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index scores were positively correlated with increases in BMI.^10,11 This close association suggests BMI may function as a practical indicator of disease severity and prognosis.^7,8,11

Psoriatic arthritis (PsA) is a major comorbidity of psoriasis that impacts disease severity and quality of life. Obesity is associated with an increased risk for PsA after accounting for traditional risk factors. Psoriatic arthritis can cause chronic mobility issues and complicate a patient’s ability to stay active. Early rheumatologist involvement may be warranted to prevent PsA development in patients with obesity and psoriasis.^11,12

Patients with psoriasis have an increased baseline risk for metabolic syndrome, including obesity, type 2 diabetes, hypertension, and dyslipidemia^11,13,14; therefore, the presence of obesity warrants regular metabolic evaluation. Unmanaged metabolic syndrome contributes to the increased prevalence of myocardial infarction, stroke, and heart failure seen with psoriasis.^13,14 Obesity also may cause obstructive sleep apnea, which can exacerbate hypertension and heart disease due to chronic hypoxia.¹¹ The interplay of these metabolic factors puts patients with psoriasis and obesity at heightened cardiovascular risk.^13,14

Both psoriasis and obesity present psychosocial challenges such as elevated rates of depression, anxiety, and body-image concerns, all of which become more pronounced when these conditions coexist. These psychological stressors may hinder a patient’s motivation for lifestyle changes or treatment adherence.¹³

Dermatology visits serve as an important opportunity to monitor obesity-related comorbidities.^13,15 Dermatologists are uniquely positioned to initiate metabolic screening while collaborating with primary care physicians for ongoing cardiometabolic management. Metabolic and cardiovascular baselines should be measured when care is established and should be followed longitudinally—these include BMI, waist circumference measurements, blood pressure, lipid panels, fasting glucose or A1C levels, and liver enzymes.^10,14,15 Regular screening for depression, suicidality, and disordered eating also is encouraged.¹³ Clinicians should follow established guidelines to identify and manage metabolic, cardiovascular, and psychological comorbidities.¹³

Impact of Obesity on Psoriasis Treatment

Obesity is a critical factor in clinical decision-making, as it consistently is associated with diminished response to numerous systemic psoriasis therapies. This reduced efficacy has been observed with conventional oral agents such as methotrexate and cyclosporine and is particularly well documented in the context of biologic therapies.^15,16 Several meta-analyses and large real-world studies have shown that higher BMI is associated with a suboptimal treatment response, with patients in higher BMI categories achieving lower rates of PASI 75 and PASI 90 than their nonobese counterparts receiving the same regimen.^15,17

This efficacy gap often is rooted in pharmacokinetic challenges. For many biologics administered via subcutaneous injection, increased BMI can lead to altered drug distribution, such as sequestration in adipose tissue. Altered distribution combined with potentially increased drug clearance can result in lower overall serum drug concentrations and subsequent underdosing for a patient’s inflammatory burden.¹⁵ This reality highlights the important distinction between fixed and weight-based dosing strategies. Therapies dosed by weight, such as infliximab, have demonstrated more consistent efficacy in populations with obesity, as the dose is escalated to match patient size.¹⁸ Despite the weight-dependent effect, recent real-world studies have suggested that fixed dosing of some IL-17A inhibitors (eg, ixekizumab) remains highly effective across BMI categories, while others (eg, secukinumab) show diminished efficacy in obese patients.^16,19 Furthermore, some real-world studies have reported an inverse relationship between elevated BMI and efficacy of IL-23 inhibitors, particularly guselkumab, while other studies reported no association.^20,21 These mixed observations support a nuanced interpretation of BMI’s role in treatment modification; consideration should be given to the specific medication and the dosing strategy over biologic class alone.

Whether obesity independently drives psoriasis severity or mainly diminishes treatment efficacy through pharmacokinetic effects remains debated. Observational studies show a dose-dependent relationship between BMI and disease severity even in untreated patients, supporting a proinflammatory role for obesity.¹⁰ Concurrently, higher BMI may predict lower responses to some fixed-dose biologics, likely due to altered distribution and sequestration in adipose tissue.^15,20 The precise contributions are challenging to delineate; both likely converge to heighten disease severity and reduce treatment response.

Beyond efficacy, obesity compounds the safety considerations of systemic treatments. Psoriasis and obesity are both strong independent risk factors for metabolic ­dysfunction–associated steatotic liver disease. This prevalent comorbidity creates a substantial clinical dilemma, as a first-line, cost-effective agent such as methotrexate carries a known risk for hepatotoxicity, which is amplified in patients with pre-existing liver steatosis.¹³ Consequently, the presence of obesity and metabolic dysfunction–associated steatotic liver disease often limits the use of methotrexate, forcing a change in therapy. Thorough baseline comorbidity screening in all patients with psoriasis and obesity is necessary to select a therapy that balances efficacy with safety.^13,14

Management Strategies

Weight management plays a pivotal role in improving psoriasis outcomes. Even modest weight loss of 5% to 10% has been shown in randomized and observational studies to substantially reduce disease severity, reflected by lower PASI and Dermatology Life Quality Index scores and enhance treatment responsiveness.^22,23 Dietary approaches emphasizing hypocaloric, Mediterranean, or ­anti-inflammatory patterns have demonstrated additional improvements in disease activity, likely through attenuation of systemic inflammation and metabolic dysregulation.²¹ Bariatric surgery provides more sustained benefits, with multiple studies reporting long-term remission or reduced psoriasis severity following substantial postoperative weight loss.^23,24

Pharmacologic weight-loss therapies, particularly glucagonlike peptide-1 receptor agonists, have emerged as potential adjuncts in psoriasis management. Although data remain limited, these agents may reduce systemic inflammation, improve insulin sensitivity, and indirectly enhance biologic response.²⁵

Conclusion

Psoriasis and obesity are interconnected chronic inflammatory conditions that share overlapping cytokine pathways and mutually exacerbate the clinical course. Systemic inflammation driven by cytokines such as TNF-α, IL-6, and IL-17 not only promotes psoriatic skin disease but also contributes to metabolic dysfunction and cardiovascular risk. In turn, excess adiposity amplifies inflammatory signaling and diminishes therapeutic response, creating a self-perpetuating cycle of disease.

Dermatologists should identify obesity-related risks early; counsel patients on lifestyle changes; initiate metabolic screening; and coordinate care across primary care, nutrition, and rheumatology. Regular screening for metabolic syndrome, cardiovascular comorbidities, and psychosocial distress should be integrated into psoriasis management. Future research should focus on personalized treatment strategies that integrate management of inflammatory skin disease with underlying metabolic health, such as optimizing biologic dosing and identifying novel targets that disrupt the pathophysiologic loop. By recognizing and addressing the shared inflammatory mechanisms of psoriasis and obesity, clinicians can improve both dermatologic and systemic outcomes for affected patients.

Psoriasis, a chronic immune-mediated skin disease, is increasingly recognized for its systemic inflammation and associated cardiometabolic risk. The global rise of obesity has revealed a critical link between these 2 conditions. Current evidence confirms that obesity is an independent risk factor that can trigger psoriasis onset, drive more severe disease, and substantially impair treatment efficacy.^1,2 This review synthesizes the latest evidence on the shared pathophysiology, clinical consequences, and integrated management strategies for patients with both psoriasis and obesity.

Pathophysiologic Links Between Psoriasis and Obesity

Emerging evidence highlights a bidirectional relationship between psoriasis and obesity rooted in overlapping inflammatory pathways. Both conditions are characterized by chronic inflammation mediated by cytokines that sustain systemic immune activation and metabolic dysfunction. This interplay creates a reciprocal process in which psoriatic inflammation promotes metabolic disturbances while obesity amplifies systemic inflammation and disease severity.³

Psoriasis may contribute to obesity through cytokine-driven metabolic alterations in insulin signaling and adipocyte function. The psoriatic immune response is dominated by T helper (Th) 1, Th17, and Th22 cell activation, leading to elevated levels of interferon-γ, tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-17, and IL-22 from keratinocytes.⁴ These cytokines contribute not only to cutaneous inflammation but also to insulin resistance and adipocyte dysfunction.⁵ Tumor necrosis factor α and IL-6 interfere with insulin signaling via activation of stress kinases (eg, IκB kinase and c-Jun N-terminal kinase), implicating these molecules in insulin resistance and weight gain.⁶ Moreover, IL-17, a central cytokine in psoriasis, has been implicated in vascular inflammation, insulin resistance, and type 2 diabetes, suggesting a mechanistic link between psoriatic inflammation and metabolic disease.⁵ Additionally, chronic systemic inflammation in psoriasis suppresses adiponectin, a protective adipokine that enhances insulin sensitivity and exerts anti-inflammatory effects by inhibiting TNF-α and IL-6 production while promoting IL-10 synthesis. Reduced adiponectin levels have consistently been observed in patients with psoriasis and concomitant obesity or metabolic syndrome.³ The resultant imbalance between proinflammatory and anti-inflammatory mediators creates a metabolic environment conducive to obesity.³

Conversely, obesity itself may intensify both the incidence and severity of psoriasis through shared inflammatory pathways. Leptin, whose expression rises proportionally with adipocyte mass, acts as a proinflammatory mediator linking obesity to psoriasis exacerbation. By promoting Th1 and Th17 cell differentiation and suppressing regulatory T-cell activity, leptin increases IL-17A, IL-6, and TNF-α production.⁷ These cytokines stimulate keratinocyte proliferation and perpetuate cutaneous inflammation, thereby intensifying disease activity. Similarly, resistin, another adipokine that is elevated in obesity, stimulates monocytes and macrophages to secrete TNF-α and IL-6, creating a proinflammatory state in the body that drives the relationship between excessive fat storage (adiposity) and the development and severity of psoriasis.⁸ In contrast, reduced adiponectin levels in obesity remove a key anti-inflammatory regulator that normally inhibits TNF-α and IL-6 synthesis and promotes IL-10 production. This deficiency provokes unrestrained cytokine activation within both adipose and cutaneous tissue, exacerbating psoriatic immune dysregulation.⁹

Free fatty acids derived from abundant adipocytes in obesity further activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)–signaling and induce oxidative stress, augmenting systemic inflammation. Adipose tissue macrophages additionally secrete IL-1Β, IL-6, and TNF-α, which promote keratinocyte proliferation and amplify the psoriatic inflammatory cascade. Importantly, anti–TNF-α therapy has been shown to improve metabolic parameters, reducing low-density lipoprotein and total cholesterol levels and enhancing insulin sensitivity, highlighting the reciprocal benefits of dampening the inflammatory signaling from TNF-α.⁵

Together, these findings highlight that psoriasis and obesity are interconnected inflammatory disorders driven by overlapping cytokine networks, most notably TNF-α, IL-6, IL-17, and IL-23, and by imbalances in adipokines such as leptin, resistin, and adiponectin (Table).

Clinical Implications of Obesity-Related Comorbidities

Higher body mass index (BMI) has been associated with an increased and earlier incidence of psoriasis. When treated as continuous variables, both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index scores were positively correlated with increases in BMI.^10,11 This close association suggests BMI may function as a practical indicator of disease severity and prognosis.^7,8,11

Psoriatic arthritis (PsA) is a major comorbidity of psoriasis that impacts disease severity and quality of life. Obesity is associated with an increased risk for PsA after accounting for traditional risk factors. Psoriatic arthritis can cause chronic mobility issues and complicate a patient’s ability to stay active. Early rheumatologist involvement may be warranted to prevent PsA development in patients with obesity and psoriasis.^11,12

Patients with psoriasis have an increased baseline risk for metabolic syndrome, including obesity, type 2 diabetes, hypertension, and dyslipidemia^11,13,14; therefore, the presence of obesity warrants regular metabolic evaluation. Unmanaged metabolic syndrome contributes to the increased prevalence of myocardial infarction, stroke, and heart failure seen with psoriasis.^13,14 Obesity also may cause obstructive sleep apnea, which can exacerbate hypertension and heart disease due to chronic hypoxia.¹¹ The interplay of these metabolic factors puts patients with psoriasis and obesity at heightened cardiovascular risk.^13,14

Both psoriasis and obesity present psychosocial challenges such as elevated rates of depression, anxiety, and body-image concerns, all of which become more pronounced when these conditions coexist. These psychological stressors may hinder a patient’s motivation for lifestyle changes or treatment adherence.¹³

Dermatology visits serve as an important opportunity to monitor obesity-related comorbidities.^13,15 Dermatologists are uniquely positioned to initiate metabolic screening while collaborating with primary care physicians for ongoing cardiometabolic management. Metabolic and cardiovascular baselines should be measured when care is established and should be followed longitudinally—these include BMI, waist circumference measurements, blood pressure, lipid panels, fasting glucose or A1C levels, and liver enzymes.^10,14,15 Regular screening for depression, suicidality, and disordered eating also is encouraged.¹³ Clinicians should follow established guidelines to identify and manage metabolic, cardiovascular, and psychological comorbidities.¹³

Impact of Obesity on Psoriasis Treatment

Obesity is a critical factor in clinical decision-making, as it consistently is associated with diminished response to numerous systemic psoriasis therapies. This reduced efficacy has been observed with conventional oral agents such as methotrexate and cyclosporine and is particularly well documented in the context of biologic therapies.^15,16 Several meta-analyses and large real-world studies have shown that higher BMI is associated with a suboptimal treatment response, with patients in higher BMI categories achieving lower rates of PASI 75 and PASI 90 than their nonobese counterparts receiving the same regimen.^15,17

This efficacy gap often is rooted in pharmacokinetic challenges. For many biologics administered via subcutaneous injection, increased BMI can lead to altered drug distribution, such as sequestration in adipose tissue. Altered distribution combined with potentially increased drug clearance can result in lower overall serum drug concentrations and subsequent underdosing for a patient’s inflammatory burden.¹⁵ This reality highlights the important distinction between fixed and weight-based dosing strategies. Therapies dosed by weight, such as infliximab, have demonstrated more consistent efficacy in populations with obesity, as the dose is escalated to match patient size.¹⁸ Despite the weight-dependent effect, recent real-world studies have suggested that fixed dosing of some IL-17A inhibitors (eg, ixekizumab) remains highly effective across BMI categories, while others (eg, secukinumab) show diminished efficacy in obese patients.^16,19 Furthermore, some real-world studies have reported an inverse relationship between elevated BMI and efficacy of IL-23 inhibitors, particularly guselkumab, while other studies reported no association.^20,21 These mixed observations support a nuanced interpretation of BMI’s role in treatment modification; consideration should be given to the specific medication and the dosing strategy over biologic class alone.

Whether obesity independently drives psoriasis severity or mainly diminishes treatment efficacy through pharmacokinetic effects remains debated. Observational studies show a dose-dependent relationship between BMI and disease severity even in untreated patients, supporting a proinflammatory role for obesity.¹⁰ Concurrently, higher BMI may predict lower responses to some fixed-dose biologics, likely due to altered distribution and sequestration in adipose tissue.^15,20 The precise contributions are challenging to delineate; both likely converge to heighten disease severity and reduce treatment response.

Beyond efficacy, obesity compounds the safety considerations of systemic treatments. Psoriasis and obesity are both strong independent risk factors for metabolic ­dysfunction–associated steatotic liver disease. This prevalent comorbidity creates a substantial clinical dilemma, as a first-line, cost-effective agent such as methotrexate carries a known risk for hepatotoxicity, which is amplified in patients with pre-existing liver steatosis.¹³ Consequently, the presence of obesity and metabolic dysfunction–associated steatotic liver disease often limits the use of methotrexate, forcing a change in therapy. Thorough baseline comorbidity screening in all patients with psoriasis and obesity is necessary to select a therapy that balances efficacy with safety.^13,14

Management Strategies

Weight management plays a pivotal role in improving psoriasis outcomes. Even modest weight loss of 5% to 10% has been shown in randomized and observational studies to substantially reduce disease severity, reflected by lower PASI and Dermatology Life Quality Index scores and enhance treatment responsiveness.^22,23 Dietary approaches emphasizing hypocaloric, Mediterranean, or ­anti-inflammatory patterns have demonstrated additional improvements in disease activity, likely through attenuation of systemic inflammation and metabolic dysregulation.²¹ Bariatric surgery provides more sustained benefits, with multiple studies reporting long-term remission or reduced psoriasis severity following substantial postoperative weight loss.^23,24

Pharmacologic weight-loss therapies, particularly glucagonlike peptide-1 receptor agonists, have emerged as potential adjuncts in psoriasis management. Although data remain limited, these agents may reduce systemic inflammation, improve insulin sensitivity, and indirectly enhance biologic response.²⁵

Conclusion

Psoriasis and obesity are interconnected chronic inflammatory conditions that share overlapping cytokine pathways and mutually exacerbate the clinical course. Systemic inflammation driven by cytokines such as TNF-α, IL-6, and IL-17 not only promotes psoriatic skin disease but also contributes to metabolic dysfunction and cardiovascular risk. In turn, excess adiposity amplifies inflammatory signaling and diminishes therapeutic response, creating a self-perpetuating cycle of disease.

Dermatologists should identify obesity-related risks early; counsel patients on lifestyle changes; initiate metabolic screening; and coordinate care across primary care, nutrition, and rheumatology. Regular screening for metabolic syndrome, cardiovascular comorbidities, and psychosocial distress should be integrated into psoriasis management. Future research should focus on personalized treatment strategies that integrate management of inflammatory skin disease with underlying metabolic health, such as optimizing biologic dosing and identifying novel targets that disrupt the pathophysiologic loop. By recognizing and addressing the shared inflammatory mechanisms of psoriasis and obesity, clinicians can improve both dermatologic and systemic outcomes for affected patients.

Rosacea is a chronic inflammatory skin disease characterized by erythema, flushing, telangiectasias, papules, pustules, and rarely, phymatous changes that primarily manifest in a centrofacial distribution.^1,2 Although establishing the true prevalence of rosacea may be challenging due to a wide spectrum of clinical manifestations, current studies estimate that it is between 5% to 6% of the global adult population and that rosacea most commonly is diagnosed in patients aged 30 and 60 years, though it occasionally can affect adolescents and children.^3,4 Although the origin and pathophysiology of rosacea remain incompletely understood, the condition arises from a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors; this interplay ultimately leads to excessive production of inflammatory and vasoactive peptides, chronic inflammation, and neurovascular hyperreactivity.^1,5-7

Identifying triggers can be valuable in managing rosacea, as avoidance of these exposures may lead to disease improvement. In this review, we highlight 4 major environmental triggers of rosacea—UV radiation exposure, temperature fluctuation, skin care practices, and diet—and their roles in its pathogenesis and management. A high-level summary of recommendations can be found in the Table.

UV Radiation Exposure

Exposure to UV radiation is a known trigger of rosacea and may worsen symptoms through several mechanisms.^8,9 It increases the production of inflammatory cytokines, which enhance the release of vascular endothelial growth factor, promoting angiogenesis and vasodilation.¹⁰ Exposure to UV radiation also contributes to tissue inflammation through the production of reactive oxygen species, further mediating inflammatory cascades and leading to immune dysregulation.^11,12 Interestingly, though the mechanisms by which UV radiation may contribute to the pathophysiology of rosacea are well described, it remains unclear whether chronic UV exposure plays a major role in the pathogenesis or disease progression of rosacea.¹ Studies have observed that increased exposure to sunlight seems to be correlated with increased severity of redness but not of papules and pustules.^13,14

Despite some uncertainty regarding the relationship between rosacea and chronic UV exposure, sun protection is a prudent recommendation in this patient population, particularly given other risks of exposure to UV radiation, such as photoaging and skin cancer.^9,15,16 Sun protection can be accomplished using broad-spectrum sunscreen (sun protection factor 50 or higher, reapplied every 2 to 4 hours) or by wearing physical protection (eg, hats, sun-protective clothing) along with avoidance of sun exposure during peak UV hours (ie, 10 am-am–4 pmpm). For individuals with more sensitive skin, using a sunscreen with inorganic filters (eg, zinc and titanium dioxide) or containing dimethicone or cyclomethicone may be helpful.¹⁷

Temperature Fluctuation

Both heat and cold exposure have been suggested as triggers for rosacea, thought to be mediated through dysregulations in neurovascular and thermal pathways, resulting in increased flushing and erythema.⁶ Skin affected by rosacea exhibits a lower threshold for temperature and pain stimuli, resulting in heightened hypersensitivity compared to normal skin.¹⁸ Exposure to heat activates thermosensitive receptors found in neuronal and nonneuronal tissues, triggering the release of vasoactive neuropeptides.¹ Among these, transient receptor potential (TRP) channels seem to play a crucial role in neurovascular reactivity and have been studied in the pathophysiology of rosacea.^1,8 Overexpression or excessive stimulation of TRPs by various environmental triggers, such as heat or cold, leads to increased neuropeptide production, ultimately contributing to persistent erythema and vascular dysfunction, as well as a burning or stinging sensation.^1,2 Moreover, rapid temperature changes, such as moving from freezing outdoor conditions into a heated environment, may also trigger flushing due to sudden vasodilation.²

Adopting behavioral strategies such as preventing overheating, minimizing sudden temperature shifts, and protecting the skin from cold can help reduce rosacea flare-ups, particularly flushing. For patients who do not achieve sufficient relief through lifestyle modifications alone, targeted pharmacologic treatments are available to help manage these symptoms. Topical α-adrenergic agonists (eg, brimonidine, oxymetazoline) are effective in reducing erythema and flushing by causing vasoconstriction.^15,19 For persistent erythema and telangiectasias, pulsed dye laser and intense pulsed light therapies can be effective treatments, as they target hemoglobin in blood vessels, leading to their destruction and a subsequent reduction in erythema.²⁰ Other medications such as topical metronidazole, azelaic acid, calcitonin-gene related peptide inhibitors, and systemic ß-blockers also can be used to treat flushing and redness.^15,21

Skin Care Practices

Due to the increased tissue inflammation and potential skin barrier dysfunction, rosacea-affected skin is highly sensitive, and skin care practices or products that disrupt the already compromised skin barrier can contribute to flare-ups. General recommendations should include use of gentle cleansers and moisturizers to prevent dry skin and improve skin barrier function²² as well as avoidance of ingredients that are common irritants and inducers of allergic contact dermatitis (eg, fragrances).⁹

Cleansing the face should be limited to 1 to 2 times daily, as excessive cleansing and use of harsh formulations with exfoliative ingredients can lead to skin irritation and worsening of symptoms.⁹ Overcleansing can lead to alterations in cutaneous pH and strip the stratum corneum of healthy components such as lipids and natural moisturizing factors. Common ingredients in cleansers that should be avoided due to their irritant nature include alcohol, acetone, benzyl alcohol, propylene glycol, and α- and ß-hydroxy acids. Instead, syndet (synthetic detergent) cleansers that contain ceramides, hyaluronic acid, or other hydrating agents with a near-physiological pH can be helpful for dry and sensitive skin.²³ Toners with high alcohol content and astringent-based products also should be avoided.

Optimal moisturizers for rosacea-affected skin should contain physiologic lipids that help replace a healthy skin barrier as well as relieve dryness and seal in moisture. Beneficial barrier-restoring ingredients include ceramides, dimethicone, cholesterol, and free fatty acids as well as humectants such as glycerin and hyaluronic acid.^9,23,24 Applying moisturizer immediately after cleansing and prior to the application of any topical treatments also can help decrease irritation.

As mentioned previously, sun protection is a cornerstone in the management of rosacea and can help reduce redness and skin irritation. Using combination formulas, such as moisturizers with a sun protection factor of at least 50, can be effective.²⁵ Additionally, products with antioxidant or anti-inflammatory ingredients such as niacinamide and allantoin can further support skin health. Lastly, formulations containing green pigments may also be beneficial, as they provide cosmetic camouflage to neutralize redness.²⁶

Dietary Factors

Several dietary factors have been proposed as triggers for rosacea, but conclusive evidence remains limited.²⁷ Foods and beverages that generate heat (eg, hot drinks, spicy foods) may exacerbate rosacea by causing vasodilation and stimulating TRP channels, resulting in flushing.¹⁸ While capsaicin, found in spicy foods, may lead to flushing through similar activation of TRP channels, current evidence has not proved a specific and consistent role in the pathogenesis of rosacea.^18,27 Similarly, cinnamaldehyde, found in cinnamon and many commercial cinnamon-containing foods as well as various fruits and vegetables, activates thermosensitive receptors that may worsen rosacea symptoms.²⁸ Other potential triggers include histamine-rich foods (eg, avocados, bananas, dried fruits, nuts, smoked fish, aged cheeses), which can lead to skin hypersensitivity and flushing, and ­formaldehyde-containing foods (eg, apples, carrots, cauliflower, shiitake mushrooms, fish), though the role these types of foods play in rosacea remains unclear.^1,29-31

The relationship between caffeine and rosacea is complex. While caffeine commonly is found in coffee, tea, and soda, some studies have suggested that coffee consumption may reduce rosacea risk due to its vasoconstrictive and anti-inflammatory effects.^28,32 In contrast, alcohol—particularly white wine and liquor—has been associated with increased rosacea risk due to its effect on vasodilation, inflammation, and oxidative stress.³³ Despite anecdotal reports, the role of dairy products in rosacea remains unclear, with conflicting studies suggesting dairy consumption may exacerbate or protect against rosacea.^27,28 Given the variability in dietary triggers, patients with rosacea may benefit from using a dietary journal to identify and avoid foods that exacerbate their symptoms, though more research is needed to establish clear recommendations.

Conclusion

Rosacea is a complex condition influenced by genetic, immune, microbial, and environmental factors. Triggers such as UV exposure, temperature fluctuations, alterations in the skin microbiome, and diet contribute to disease exacerbation through mechanisms like vasodilation, neurogenic inflammation, and immune dysregulation. These triggers often interact, compounding their effects and making symptom management more challenging and multifaceted.

Successful rosacea treatment relies on identifying and minimizing patient-specific triggers, as lifestyle modifications can reduce flare-ups and improve outcomes. When combined with interventional, oral, and topical therapies, these adjustments enhance treatment effectiveness and contribute to better long-term disease control. Clinicians should adopt a personalized holistic approach by educating patients on common triggers, recommending lifestyle changes, and integrating medical treatments as necessary. Future research should continue exploring the relationships between rosacea and environmental factors to develop more targeted and evidence-based recommendations.

Rosacea is a chronic inflammatory skin disease characterized by erythema, flushing, telangiectasias, papules, pustules, and rarely, phymatous changes that primarily manifest in a centrofacial distribution.^1,2 Although establishing the true prevalence of rosacea may be challenging due to a wide spectrum of clinical manifestations, current studies estimate that it is between 5% to 6% of the global adult population and that rosacea most commonly is diagnosed in patients aged 30 and 60 years, though it occasionally can affect adolescents and children.^3,4 Although the origin and pathophysiology of rosacea remain incompletely understood, the condition arises from a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors; this interplay ultimately leads to excessive production of inflammatory and vasoactive peptides, chronic inflammation, and neurovascular hyperreactivity.^1,5-7

Identifying triggers can be valuable in managing rosacea, as avoidance of these exposures may lead to disease improvement. In this review, we highlight 4 major environmental triggers of rosacea—UV radiation exposure, temperature fluctuation, skin care practices, and diet—and their roles in its pathogenesis and management. A high-level summary of recommendations can be found in the Table.

UV Radiation Exposure

Exposure to UV radiation is a known trigger of rosacea and may worsen symptoms through several mechanisms.^8,9 It increases the production of inflammatory cytokines, which enhance the release of vascular endothelial growth factor, promoting angiogenesis and vasodilation.¹⁰ Exposure to UV radiation also contributes to tissue inflammation through the production of reactive oxygen species, further mediating inflammatory cascades and leading to immune dysregulation.^11,12 Interestingly, though the mechanisms by which UV radiation may contribute to the pathophysiology of rosacea are well described, it remains unclear whether chronic UV exposure plays a major role in the pathogenesis or disease progression of rosacea.¹ Studies have observed that increased exposure to sunlight seems to be correlated with increased severity of redness but not of papules and pustules.^13,14

Despite some uncertainty regarding the relationship between rosacea and chronic UV exposure, sun protection is a prudent recommendation in this patient population, particularly given other risks of exposure to UV radiation, such as photoaging and skin cancer.^9,15,16 Sun protection can be accomplished using broad-spectrum sunscreen (sun protection factor 50 or higher, reapplied every 2 to 4 hours) or by wearing physical protection (eg, hats, sun-protective clothing) along with avoidance of sun exposure during peak UV hours (ie, 10 am-am–4 pmpm). For individuals with more sensitive skin, using a sunscreen with inorganic filters (eg, zinc and titanium dioxide) or containing dimethicone or cyclomethicone may be helpful.¹⁷

Temperature Fluctuation

Both heat and cold exposure have been suggested as triggers for rosacea, thought to be mediated through dysregulations in neurovascular and thermal pathways, resulting in increased flushing and erythema.⁶ Skin affected by rosacea exhibits a lower threshold for temperature and pain stimuli, resulting in heightened hypersensitivity compared to normal skin.¹⁸ Exposure to heat activates thermosensitive receptors found in neuronal and nonneuronal tissues, triggering the release of vasoactive neuropeptides.¹ Among these, transient receptor potential (TRP) channels seem to play a crucial role in neurovascular reactivity and have been studied in the pathophysiology of rosacea.^1,8 Overexpression or excessive stimulation of TRPs by various environmental triggers, such as heat or cold, leads to increased neuropeptide production, ultimately contributing to persistent erythema and vascular dysfunction, as well as a burning or stinging sensation.^1,2 Moreover, rapid temperature changes, such as moving from freezing outdoor conditions into a heated environment, may also trigger flushing due to sudden vasodilation.²

Adopting behavioral strategies such as preventing overheating, minimizing sudden temperature shifts, and protecting the skin from cold can help reduce rosacea flare-ups, particularly flushing. For patients who do not achieve sufficient relief through lifestyle modifications alone, targeted pharmacologic treatments are available to help manage these symptoms. Topical α-adrenergic agonists (eg, brimonidine, oxymetazoline) are effective in reducing erythema and flushing by causing vasoconstriction.^15,19 For persistent erythema and telangiectasias, pulsed dye laser and intense pulsed light therapies can be effective treatments, as they target hemoglobin in blood vessels, leading to their destruction and a subsequent reduction in erythema.²⁰ Other medications such as topical metronidazole, azelaic acid, calcitonin-gene related peptide inhibitors, and systemic ß-blockers also can be used to treat flushing and redness.^15,21

Skin Care Practices

Due to the increased tissue inflammation and potential skin barrier dysfunction, rosacea-affected skin is highly sensitive, and skin care practices or products that disrupt the already compromised skin barrier can contribute to flare-ups. General recommendations should include use of gentle cleansers and moisturizers to prevent dry skin and improve skin barrier function²² as well as avoidance of ingredients that are common irritants and inducers of allergic contact dermatitis (eg, fragrances).⁹

Cleansing the face should be limited to 1 to 2 times daily, as excessive cleansing and use of harsh formulations with exfoliative ingredients can lead to skin irritation and worsening of symptoms.⁹ Overcleansing can lead to alterations in cutaneous pH and strip the stratum corneum of healthy components such as lipids and natural moisturizing factors. Common ingredients in cleansers that should be avoided due to their irritant nature include alcohol, acetone, benzyl alcohol, propylene glycol, and α- and ß-hydroxy acids. Instead, syndet (synthetic detergent) cleansers that contain ceramides, hyaluronic acid, or other hydrating agents with a near-physiological pH can be helpful for dry and sensitive skin.²³ Toners with high alcohol content and astringent-based products also should be avoided.

Optimal moisturizers for rosacea-affected skin should contain physiologic lipids that help replace a healthy skin barrier as well as relieve dryness and seal in moisture. Beneficial barrier-restoring ingredients include ceramides, dimethicone, cholesterol, and free fatty acids as well as humectants such as glycerin and hyaluronic acid.^9,23,24 Applying moisturizer immediately after cleansing and prior to the application of any topical treatments also can help decrease irritation.

As mentioned previously, sun protection is a cornerstone in the management of rosacea and can help reduce redness and skin irritation. Using combination formulas, such as moisturizers with a sun protection factor of at least 50, can be effective.²⁵ Additionally, products with antioxidant or anti-inflammatory ingredients such as niacinamide and allantoin can further support skin health. Lastly, formulations containing green pigments may also be beneficial, as they provide cosmetic camouflage to neutralize redness.²⁶

Dietary Factors

Several dietary factors have been proposed as triggers for rosacea, but conclusive evidence remains limited.²⁷ Foods and beverages that generate heat (eg, hot drinks, spicy foods) may exacerbate rosacea by causing vasodilation and stimulating TRP channels, resulting in flushing.¹⁸ While capsaicin, found in spicy foods, may lead to flushing through similar activation of TRP channels, current evidence has not proved a specific and consistent role in the pathogenesis of rosacea.^18,27 Similarly, cinnamaldehyde, found in cinnamon and many commercial cinnamon-containing foods as well as various fruits and vegetables, activates thermosensitive receptors that may worsen rosacea symptoms.²⁸ Other potential triggers include histamine-rich foods (eg, avocados, bananas, dried fruits, nuts, smoked fish, aged cheeses), which can lead to skin hypersensitivity and flushing, and ­formaldehyde-containing foods (eg, apples, carrots, cauliflower, shiitake mushrooms, fish), though the role these types of foods play in rosacea remains unclear.^1,29-31

The relationship between caffeine and rosacea is complex. While caffeine commonly is found in coffee, tea, and soda, some studies have suggested that coffee consumption may reduce rosacea risk due to its vasoconstrictive and anti-inflammatory effects.^28,32 In contrast, alcohol—particularly white wine and liquor—has been associated with increased rosacea risk due to its effect on vasodilation, inflammation, and oxidative stress.³³ Despite anecdotal reports, the role of dairy products in rosacea remains unclear, with conflicting studies suggesting dairy consumption may exacerbate or protect against rosacea.^27,28 Given the variability in dietary triggers, patients with rosacea may benefit from using a dietary journal to identify and avoid foods that exacerbate their symptoms, though more research is needed to establish clear recommendations.

Conclusion

Rosacea is a complex condition influenced by genetic, immune, microbial, and environmental factors. Triggers such as UV exposure, temperature fluctuations, alterations in the skin microbiome, and diet contribute to disease exacerbation through mechanisms like vasodilation, neurogenic inflammation, and immune dysregulation. These triggers often interact, compounding their effects and making symptom management more challenging and multifaceted.

Successful rosacea treatment relies on identifying and minimizing patient-specific triggers, as lifestyle modifications can reduce flare-ups and improve outcomes. When combined with interventional, oral, and topical therapies, these adjustments enhance treatment effectiveness and contribute to better long-term disease control. Clinicians should adopt a personalized holistic approach by educating patients on common triggers, recommending lifestyle changes, and integrating medical treatments as necessary. Future research should continue exploring the relationships between rosacea and environmental factors to develop more targeted and evidence-based recommendations.

Rosacea is a chronic inflammatory skin disease characterized by erythema, flushing, telangiectasias, papules, pustules, and rarely, phymatous changes that primarily manifest in a centrofacial distribution.^1,2 Although establishing the true prevalence of rosacea may be challenging due to a wide spectrum of clinical manifestations, current studies estimate that it is between 5% to 6% of the global adult population and that rosacea most commonly is diagnosed in patients aged 30 and 60 years, though it occasionally can affect adolescents and children.^3,4 Although the origin and pathophysiology of rosacea remain incompletely understood, the condition arises from a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors; this interplay ultimately leads to excessive production of inflammatory and vasoactive peptides, chronic inflammation, and neurovascular hyperreactivity.^1,5-7

Identifying triggers can be valuable in managing rosacea, as avoidance of these exposures may lead to disease improvement. In this review, we highlight 4 major environmental triggers of rosacea—UV radiation exposure, temperature fluctuation, skin care practices, and diet—and their roles in its pathogenesis and management. A high-level summary of recommendations can be found in the Table.

UV Radiation Exposure

Exposure to UV radiation is a known trigger of rosacea and may worsen symptoms through several mechanisms.^8,9 It increases the production of inflammatory cytokines, which enhance the release of vascular endothelial growth factor, promoting angiogenesis and vasodilation.¹⁰ Exposure to UV radiation also contributes to tissue inflammation through the production of reactive oxygen species, further mediating inflammatory cascades and leading to immune dysregulation.^11,12 Interestingly, though the mechanisms by which UV radiation may contribute to the pathophysiology of rosacea are well described, it remains unclear whether chronic UV exposure plays a major role in the pathogenesis or disease progression of rosacea.¹ Studies have observed that increased exposure to sunlight seems to be correlated with increased severity of redness but not of papules and pustules.^13,14

Despite some uncertainty regarding the relationship between rosacea and chronic UV exposure, sun protection is a prudent recommendation in this patient population, particularly given other risks of exposure to UV radiation, such as photoaging and skin cancer.^9,15,16 Sun protection can be accomplished using broad-spectrum sunscreen (sun protection factor 50 or higher, reapplied every 2 to 4 hours) or by wearing physical protection (eg, hats, sun-protective clothing) along with avoidance of sun exposure during peak UV hours (ie, 10 am-am–4 pmpm). For individuals with more sensitive skin, using a sunscreen with inorganic filters (eg, zinc and titanium dioxide) or containing dimethicone or cyclomethicone may be helpful.¹⁷

Temperature Fluctuation

Both heat and cold exposure have been suggested as triggers for rosacea, thought to be mediated through dysregulations in neurovascular and thermal pathways, resulting in increased flushing and erythema.⁶ Skin affected by rosacea exhibits a lower threshold for temperature and pain stimuli, resulting in heightened hypersensitivity compared to normal skin.¹⁸ Exposure to heat activates thermosensitive receptors found in neuronal and nonneuronal tissues, triggering the release of vasoactive neuropeptides.¹ Among these, transient receptor potential (TRP) channels seem to play a crucial role in neurovascular reactivity and have been studied in the pathophysiology of rosacea.^1,8 Overexpression or excessive stimulation of TRPs by various environmental triggers, such as heat or cold, leads to increased neuropeptide production, ultimately contributing to persistent erythema and vascular dysfunction, as well as a burning or stinging sensation.^1,2 Moreover, rapid temperature changes, such as moving from freezing outdoor conditions into a heated environment, may also trigger flushing due to sudden vasodilation.²

Adopting behavioral strategies such as preventing overheating, minimizing sudden temperature shifts, and protecting the skin from cold can help reduce rosacea flare-ups, particularly flushing. For patients who do not achieve sufficient relief through lifestyle modifications alone, targeted pharmacologic treatments are available to help manage these symptoms. Topical α-adrenergic agonists (eg, brimonidine, oxymetazoline) are effective in reducing erythema and flushing by causing vasoconstriction.^15,19 For persistent erythema and telangiectasias, pulsed dye laser and intense pulsed light therapies can be effective treatments, as they target hemoglobin in blood vessels, leading to their destruction and a subsequent reduction in erythema.²⁰ Other medications such as topical metronidazole, azelaic acid, calcitonin-gene related peptide inhibitors, and systemic ß-blockers also can be used to treat flushing and redness.^15,21

Skin Care Practices

Due to the increased tissue inflammation and potential skin barrier dysfunction, rosacea-affected skin is highly sensitive, and skin care practices or products that disrupt the already compromised skin barrier can contribute to flare-ups. General recommendations should include use of gentle cleansers and moisturizers to prevent dry skin and improve skin barrier function²² as well as avoidance of ingredients that are common irritants and inducers of allergic contact dermatitis (eg, fragrances).⁹

Cleansing the face should be limited to 1 to 2 times daily, as excessive cleansing and use of harsh formulations with exfoliative ingredients can lead to skin irritation and worsening of symptoms.⁹ Overcleansing can lead to alterations in cutaneous pH and strip the stratum corneum of healthy components such as lipids and natural moisturizing factors. Common ingredients in cleansers that should be avoided due to their irritant nature include alcohol, acetone, benzyl alcohol, propylene glycol, and α- and ß-hydroxy acids. Instead, syndet (synthetic detergent) cleansers that contain ceramides, hyaluronic acid, or other hydrating agents with a near-physiological pH can be helpful for dry and sensitive skin.²³ Toners with high alcohol content and astringent-based products also should be avoided.

Optimal moisturizers for rosacea-affected skin should contain physiologic lipids that help replace a healthy skin barrier as well as relieve dryness and seal in moisture. Beneficial barrier-restoring ingredients include ceramides, dimethicone, cholesterol, and free fatty acids as well as humectants such as glycerin and hyaluronic acid.^9,23,24 Applying moisturizer immediately after cleansing and prior to the application of any topical treatments also can help decrease irritation.

As mentioned previously, sun protection is a cornerstone in the management of rosacea and can help reduce redness and skin irritation. Using combination formulas, such as moisturizers with a sun protection factor of at least 50, can be effective.²⁵ Additionally, products with antioxidant or anti-inflammatory ingredients such as niacinamide and allantoin can further support skin health. Lastly, formulations containing green pigments may also be beneficial, as they provide cosmetic camouflage to neutralize redness.²⁶

Dietary Factors

Several dietary factors have been proposed as triggers for rosacea, but conclusive evidence remains limited.²⁷ Foods and beverages that generate heat (eg, hot drinks, spicy foods) may exacerbate rosacea by causing vasodilation and stimulating TRP channels, resulting in flushing.¹⁸ While capsaicin, found in spicy foods, may lead to flushing through similar activation of TRP channels, current evidence has not proved a specific and consistent role in the pathogenesis of rosacea.^18,27 Similarly, cinnamaldehyde, found in cinnamon and many commercial cinnamon-containing foods as well as various fruits and vegetables, activates thermosensitive receptors that may worsen rosacea symptoms.²⁸ Other potential triggers include histamine-rich foods (eg, avocados, bananas, dried fruits, nuts, smoked fish, aged cheeses), which can lead to skin hypersensitivity and flushing, and ­formaldehyde-containing foods (eg, apples, carrots, cauliflower, shiitake mushrooms, fish), though the role these types of foods play in rosacea remains unclear.^1,29-31

The relationship between caffeine and rosacea is complex. While caffeine commonly is found in coffee, tea, and soda, some studies have suggested that coffee consumption may reduce rosacea risk due to its vasoconstrictive and anti-inflammatory effects.^28,32 In contrast, alcohol—particularly white wine and liquor—has been associated with increased rosacea risk due to its effect on vasodilation, inflammation, and oxidative stress.³³ Despite anecdotal reports, the role of dairy products in rosacea remains unclear, with conflicting studies suggesting dairy consumption may exacerbate or protect against rosacea.^27,28 Given the variability in dietary triggers, patients with rosacea may benefit from using a dietary journal to identify and avoid foods that exacerbate their symptoms, though more research is needed to establish clear recommendations.

Conclusion

Rosacea is a complex condition influenced by genetic, immune, microbial, and environmental factors. Triggers such as UV exposure, temperature fluctuations, alterations in the skin microbiome, and diet contribute to disease exacerbation through mechanisms like vasodilation, neurogenic inflammation, and immune dysregulation. These triggers often interact, compounding their effects and making symptom management more challenging and multifaceted.

Successful rosacea treatment relies on identifying and minimizing patient-specific triggers, as lifestyle modifications can reduce flare-ups and improve outcomes. When combined with interventional, oral, and topical therapies, these adjustments enhance treatment effectiveness and contribute to better long-term disease control. Clinicians should adopt a personalized holistic approach by educating patients on common triggers, recommending lifestyle changes, and integrating medical treatments as necessary. Future research should continue exploring the relationships between rosacea and environmental factors to develop more targeted and evidence-based recommendations.

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰

Clinical simulation is a technique, not a technology, used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive fashion.¹ Simulation is widely used in medical education and spans a spectrum of sophistication, from simple reproduction of isolated body parts to high-fidelity human patient simulators that replicate whole body appearance and variable physiological parameters.^2,3

Simulation-based medical education can be a valuable tool for safe health care delivery.⁴Simulation-based education is typically provided via 5 modalities: mannequins, computer-based mannequins, standardized patients, computer-based simulators, and software-based simulations. Simulation technology increases procedural skill by allowing for deliberate practice in a safe environment.⁵ Mastery learning is a stringent form of competency-based education that requires trainees to acquire clinical skill measured against a fixed achievement standard.⁶ In mastery learning, educational practice time varies but results are uniform. This approach improves patient outcomes and is more effective than clinical training alone.^7-9

Advanced simulation models are helpful tools for neurologic education and training, especially for emergency department encounters.¹⁰ In recent years, advanced simulation models have been applied in various fields of medicine, especially emergency medicine and anesthesia.^11-14

Acute neurology

In acute neurologic conditions (eg, stroke, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory failure) clinical outcomes are highly time dependent; consequently, a reduction in treatment delays can improve patient care. The application of simulation methodology allows trainees to address acute and potentially life-threatening emergencies in a safe, controlled, and reproducible environment. In addition to improving trainees’ knowledge base, simulation also helps to enhance team skills, communication, multidisciplinary collaboration, and leadership. Research has shown that deliberate practice leads to a decrease in clinical errors and improved procedural performance in the operating room.^8,15 These results can be extrapolated to acute neurology settings to improve adherence to set protocols, thus streamlining management in acute settings.

Scenarios can be built to teach skills such as eliciting an appropriate history, establishing inclusion or exclusion criteria for the use of certain medications, evaluating neuroimaging and laboratory studies (while avoiding related common pitfalls), and managing treatment complications. Simulation also provides an opportunity for interprofessional education by training nurses and collaborative staff. It can be used to enhance nontechnical skills (eg, communication, situation awareness, decision making, and leadership) that further contribute to patient safety. 

Simulation can be performed with the help of mannequins such as the SimMan 3G(Laerdal), which can display neurologic symptoms and physiological findings, or live actors who portray a patient by mimicking focal neurologic deficits.^16,17 A briefing familiarizes the trainees with the equipment and explains the simulation process. The documentation and equipment are the same as that which is used in emergency departments or intensive care units. 

Once the simulation is completed, a trainee’s performance is checked against a critical action checklist before a debriefing process during which the scenario is reviewed and learning goals are assessed. Immediate feedback is given to trainees to identify weaknesses and the simulation is repeated if multiple critical action items are missed. (Figure).¹⁷

RESIDENCY TRAINING

Simulation training in stroke is mandatory in some residency programs for neurology postgraduate year (PGY) 2 residents.¹⁸ These simulations are a part of a boot camp for incoming neurology residents after completing an internal medicine internship. The simulation program is not standardized across various training programs. The European Stroke Organization Simulation Committee has published an opinion paper with a consensus of experts about the implementation of simulation techniques in the stroke field.^19,20 Residents participating in these mandatory programs are required to complete certification in the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale, including a pretest that assesses their knowledge of acute stroke protocols prior to live simulation.¹⁷ A stepwise algorithm that incorporates faculty specialized in the field is used to evaluate and debrief the simulation.

Stroke vignettes are typically selected by the vascular neurology attending physician to cover thrombolytic therapy (indications and contraindications), mechanical thrombectomy, early arterial blood pressure management, anticoagulant reversal protocols, and management of thrombolytic complications (eg, neurologic worsening). Nursing staff is educated on the acute stroke protocol. Computed tomography (CT) and CT angiography scans are retrieved from teaching files. These are provided as live responses along with pertinent laboratory work, vital signs, and electrocardiogram tracings. Trainee performance is based on adherence to a critical action checklist, which includes (but is not limited to) identification of relative and absolute contraindications of thrombolytic treatments, estimation of NIHSS within 5 minutes of arrival, and consideration of candidacy for endovascular intervention.¹⁷

EVIDENCE FOR SIMULATION TRAINING

Simulations for acute ischemic stroke also improve cohesive teamwork to improve the door-to-needle and door-to-puncture time. A retrospective analysis involving first-year neurology residents at a comprehensive stroke center that compared patient cohort data before and after implementation of simulation training found that there was an improvement in door-to-needle time after implementation of stroke simulation training program by nearly 10 minutes.¹⁷ This was likely due to improvement in the comfort of the flow of management across multidisciplinary teams.

Discussing goals of care, communicating poor prognosis or complex decisions with distraught family members or patients requires practice. Simulation programs with video playback help focus on trainee’s body language, avoiding medical jargon and handling ethical dilemmas while adjusting the communication style to the patient’s personality.²⁰ Enhanced communication skills improve patient satisfaction, trust, and adherence to treatments, all of which lead to better outcomes.²¹

Simulation has been effectively used as a training tool for recognizing and managing acute neuromuscular respiratory failure. These scenarios emphasize the importance of obtaining a focused clinical history, performing key neurological assessments (such as neck flexion strength and breath counting), evaluating pulmonary function tests, and identifying when to initiate ventilatory support.²² In a study designed as a simulation-based learning curriculum for status epilepticus, there was an improvement in the performance of PGY-2 residents after completing the curriculum from a median of 44.2% at pretest to 94.2% at posttest.²³ In this curriculum, an emphasis was placed on the following: recognizing the delay in identification and treatment of status epilepticus; evaluating contraindications of certain antiseizure medication (ASM) based on history or laboratory work; giving first-line ASM within 5 minutes of seizure onset; airway and blood pressure assessment; suctioning the patient; use of second-line ASMs after first-line has failed; ordering a head CT and re-evaluating the case with postload ASM level; ordering a stat electroencephalography (EEG); and communicating the decision regarding patient disposition/level of care.²⁴

There is a growing need for well designed simulation education programs targeted at the management of disorders requiring acute neurologic care, including not only stroke and status epilepticus, but also traumatic brain injury, subarachnoid hemorrhage, neuromuscular respiratory failure, flare of multiple sclerosis, acutely elevated intracranial pressure, malignant cerebral infarction, deterioration of Parkinson disease, and brain death evaluation with family counseling.²⁵ This novel approach to teaching provides an opportunity to learn in addition to remediation with repetition of scenario and might be used for maintenance of recertification programs.

PROCEDURAL SKILLs

Perhaps one of the most studied uses for simulation in neurology is in procedural skills. This extends beyond neurology trainees and can include pulmonary critical care fellows, pediatric residents, and internal medicine residents receiving training in neurology-based procedures such as lumbar punctures (LPs). Other examples of neurology procedures and protocols in which simulation has been studied include fundoscopy, brain death evaluation, EEG interpretation in context of status epilepticus, and simulated stroke code responses. Additional procedures that lack research but may benefit from simulation-based training include the use of Doppler ultrasound and botulinum toxin injections practiced on mannequins.

Proficiency in LP procedural skills has been extensively studied by multiple institutions, with trainee levels ranging from medical students to fellows. One study in France enrolled 115 medical students without prior LP experience and randomized them to either a simulation or a control group.²⁶ Those in the simulation group received instruction using a mannequin, and those in the control group received clinical training through hospital rotations. Both groups received an email containing literature-based information on the procedure as well as a self-assessment questionnaire before participating in either educational program. 

The study showed that those students who received simulation training had a success rate of 67% on their first LP on a live patient compared with a success rate of 14% in those with traditional training. Students receiving simulation training required less assistance during the procedure from a supervisor and had higher satisfaction rates and confidence in their procedural skills.²⁶

Another study of 128 medical students at the University of Pittsburgh found that a hybrid LP simulation significantly improved students’ confidence and perceived skill in performing LPs, obtaining informed consent, and electronic order entry. For example, confidence with LP increased from 5.95% presimulation to 90% postsimulation, with 58.24% of students reporting an improvement from minimal or no confidence to average or better (P < .001). Similarly, the proportion of students who felt able to perform LP with minimal or no assistance rose from 0% to 38.57% (P < .001). Confidence and perceived skill in obtaining informed consent and electronic order entry also saw significant gains. Although real-world skill assessments were limited by low survey response rates, preceptor evaluations and follow-up surveys suggested that students who participated in the simulation were more likely to perform these tasks independently or with minimal supervision during clinical rotations.²⁷

Research on simulation training involving nonneurology residents is also encouraging. One study compared the LP skills of traditionally trained neurology residents (PGY-2 to PGY-4) to internal medicine residents (PGY-1) who underwent simulation on a mannequin.²⁸ The internal medicine residents first underwent a pretest on LP performance, watched an educational video, underwent an LP demonstration, and practiced on a mannequin with feedback. The neurology residents completed the checklist-style pretest and performed an LP on a mannequin. Internal medicine residents were found to increase their pretest scores from a mean of 46.3% to 95.7% following training, whereas neurology residents scored a mean of 65.4%. More than half of neurology residents were unable to identify the correct anatomic location or standard cerebrospinal fluid (CSF) tests to be ordered on a routine LP.²⁸

A pediatric resident study in Canada found that following simulation-based training, LP procedural skill improved in 15 of 16 residents tested, and PGY-1 residents showed a reduction in anxiety related to performing the procedure.²⁹

Virtual Reality

An additional tool for simulation is the use of virtual reality (VR) in combination with mannequins. A French study used videos of LPs on actual patients, from equipment set up to final CSF collection and termination of the procedure.³⁰ These videos included a 360-degree view of the procedure. The short video was administered through a VR device (the Oculus Go headset by Microsoft) or by a YouTube video (if VR was not desired).

Participants in the study watched the video then performed an LP on a mannequin. Those who used the VR option had minimal adverse effects (eg, low rates of cybersickness, blurred vision, nausea) and high satisfaction regarding their training environment.³⁰Another VR-based program is the vascular intervention system trainer, which allows clinicians to use endovascular devices and simulate procedures such as thrombectomies. VR simulation is used for trainees and to retrain experienced physicians in performance of high-risk procedures.³¹

Fundoscopic and Ultrasound Simulations

The AR403 eye stimulator device for fundoscopic examinations is a mannequin-based simulation.³² In a single-center, prospective, single-blind study of neurology and pediatric neurology residents, trainees were split into control and intervention groups, with the intervention group receiving simulator training. Both groups received video lectures on fundoscopy techniques. Pre- and postintervention measurements included knowledge, skill, and total scores on the skills assessment. Of the 48 trainees who participated, the intervention group demonstrated significantly higher increases in skills (P = .01) and total (P = .02) scores, although knowledge scores did not improve. The intervention group also reported higher comfort levels, higher confidence, and higher success rates.

Areas that would benefit from simulation training and development include ultrasound training, such as transcranial Doppler evaluation. In a national survey of residents in anesthesia and critical care, trainees reported that simulation was not frequently used in ultrasound training and that bedside teaching was more common. Interestingly, there was a discrepancy between the opinions of residents and program directors. The program directors felt simulation was in fact used (18.2% of program directors reported this vs 5.3% of trainees).³³

A new program, the NewroSim (Gaumard), is a computer-based model of cerebral perfusion that may be a useful tool in this setting. It can simulate blood flow velocities, including pathologic ones, both with a mannequin or without.³⁴

Another potential area for development is the use of mannequins to teach botulinum toxin injections for migraine, dystonia and spasticity in a training environment This is typically led by pharmaceutical representatives who are not necessarily clinicians. Residents and fellows may benefit instead from clinician-led education during their training programs.

Simulation in Patient Communication

Simulation provides a realistic environment for teaching rapid decision-making, leadership, and appropriate management of acutely ill neurologic patients; this includes the communication skills needed in response to neurologic injury.³⁵ Simulation can be particularly useful in situations involving brain death determination, where the communication techniques differ significantly from those used in shared decision-making. Simulation provides a low-stakes setting for clinicians to practice the process of brain death determination and communication, leading to improved confidence and knowledge.³⁶

In the context of acute neurologic emergencies, simulation exercises have been used to investigate the consistency of prognostication across a spectrum of neurology physicians. These exercises revealed that acute neuroprognostication is highly variable and often inaccurate among neurology clinicians, suggesting a potential area for improvement through further simulation training.³⁷

FUTURE DIRECTIONS

Simulation education in neurology can be directed towards learners at all levels, including medical students, residents, fellows, nurses, and medical technologists. In addition, simulation has great value to different disciplines, including emergency medicine, intensive care, and psychiatry. In our view simulation is not being used to full potential in neurology.

Simulation can be used to expose clinicians to rare pathology, play an integral role in competency-based evaluations, and serve as the foundation for simulation-based neurology curriculums, teleneurology simulation training programs, and team training for neurologic emergencies.³⁸Another under-recognized aspect of neurology education is teaching interpersonal communication and professionalism. A survey conducted at a neurology department (20 residents and 73 faculty respondents) asked about residents’ comfort level in performing a number of interpersonal communication and professionalism tasks.³⁸ While none of the residents said they were “very uncomfortable” with these tasks, only 1 resident reported being “very comfortable.” In addition, fewer than 50% noted that they had been directly observed by a faculty member while performing these tasks. The results prompted the facility to develop a simulation curriculum that including observation and feedback from 8 objective structured clinical examinations at a simulation center. A standardized professional simulated the role of a patient, caregiver, medical student, or a faculty member. Residents indicated in postsimulation surveys that it was very useful, and a majority voted for the activity to be repeated for future classes.³⁸

Simulation models may also provide a more objective method to evaluate neurology residents. Accreditation Council for Graduate Medical Education has provided Milestones that are used for assessment of neurology residents. Most of the programs rely on end-of-rotation faculty evaluations. These are subjective evaluations, rely on chance evaluations and may not reflect the exact caliber of a trainee in different clinical situations. Simulation models can serve as alternatives to provide an objective and accurate assessment of resident’s competency in different neurologic scenarios. 

In a study of PGY-4 neurology residents from 3 tertiary care academic medical centers were evaluated using simulation-based assessment. Their skills in identifying and managing status epilepticus were assessed via a simulation-based model and compared with clinical experience. No graduating neurology residents were able to meet or exceed the minimum passing score during the testing. It was suggested that end-of-rotation evaluations are inadequate for assigning level of Milestones.²⁴ To move forward with use of simulation-based assessments, these models need to be trialed more extensively and validated. 

Morris et al developed simulations for assessment in neurocritical care.³⁹ Ten evaluative simulation cases were developed. Researchers reported on 64 trainee participants in 274 evaluative simulation scenarios. The participants were very satisfied with the cases, found them to be very realistic and appropriately difficult. Interrater reliability was acceptable for both checklist action items and global rating scales. The researchers concluded that they were able to demonstrate validity evidence via the 10 simulation cases for assessment in neurologic emergencies.³⁹ It is the authors’ belief that the future of residents’ competency assessment should include more widespread use of similar simulation models. 

Finally, VR and augmented reality (AR) have shown promise in various fields, including neurology. In neurology, these technologies are being explored for applications in rehabilitation, therapy, and medical training. Ongoing research aims to leverage these technologies for improved patient outcomes and medical education. Virtual simulations can recreate neurologic scenarios, allowing learners to interact with 3-dimensional (3D) models of the brain or experience virtual patient cases. AR can enhance traditional learning materials by overlaying digital information onto real-world objects, aiding in the understanding of complex neuroanatomy and medical concepts. These technologies contribute to more engaging and effective neurology education.³⁹In a study of 84 graduate medical students divided into 3 groups, the first group attended a traditional lecture on neuroanatomy, the second group was shown VR-based 3D images, and the third group had a VR-based, interactive and stereoscopic session.⁴⁰ Groups 2 and 3 showed the highest mean scores in evaluations and differed significantly from Group 1 (P < .05). Groups 2 and 3 did not differ significantly from each other. The researchers concluded that VR-based resources for teaching neuroanatomy fostered significantly higher learning when compared to the traditional methods.⁴⁰