Article

Inpatient consultative dermatology has advanced as a subspecialty and increasingly gained recognition in recent years. Since its founding in 2009, the Society of Dermatology Hospitalists has fostered research and education in hospital dermatology. Last year, we reviewed the 2022-2023 literature with a focus on developments in severe cutaneous adverse reactions, supportive oncodermatology, cost of inpatient services, and teledermatology.¹ In this review, we highlight 3 areas of interest from the 2023-2024 literature: severe cutaneous adverse drug reactions, skin and soft tissue infections, and autoimmune blistering diseases (AIBDs).

Severe Cutaneous Adverse Drug Reactions

Adverse drug reactions are among the most common diagnoses encountered by inpatient dermatology consultants.^2,3 Severe cutaneous adverse drug reactions are associated with substantial morbidity and mortality. Efforts to characterize these conditions and standardize their diagnosis and management continue to be a major focus of ongoing research.

A single-center retrospective analysis of 102 cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome evaluated differences in clinical manifestations depending on the culprit drug, offering insights into the heterogeneity of DRESS syndrome and the potential for diagnostic uncertainty.⁴ The shortest median latency was observed in a case caused by penicillin and cephalosporins (12 and 18 days, respectively), while DRESS syndrome secondary to allopurinol had the longest median latency (36 days). Nonsteroidal anti-inflammatory drug–induced DRESS syndrome was associated with the shortest hospital stay (6.5 days), while cephalosporin and vancomycin cases had the highest mortality rates.⁴

In the first international Delphi consensus study on the diagnostic workup, severity assessment, and management of DRESS syndrome, 54 dermatology and/or allergy experts reached consensus on 93 statements.⁵ Specific recommendations included basic evaluation with complete blood count with differential, kidney and liver function parameters, and electrocardiogram for all patients with suspected DRESS syndrome, with additional complementary workup considered in patients with evidence of specific organ damage and/or severe disease. In the proposed DRESS syndrome severity grading scheme, laboratory values that reached consensus for inclusion were hemoglobin, neutrophil, and platelet counts and creatinine, transaminases, and alkaline phosphatase levels. Although treatment of DRESS syndrome should be based on assessed disease severity, treatment with corticosteroids should be initiated in all patients with confirmed DRESS syndrome. Cyclosporine, antibodies interfering with the IL-5 axis, and intravenous immunoglobulins can be considered in patients with corticosteroid-refractory DRESS syndrome, and antiviral treatment can be considered in patients with a high serum cytomegalovirus viral load. Regularly following up with laboratory evaluation of involved organs; screening for autoantibodies, thyroid dysfunction, and steroid adverse effects; and offering of psychological support also were consensus recommendations.⁵

Identifying causative agents in drug hypersensitivity reactions remains challenging. A retrospective cohort study of 48 patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) highlighted the need for a systematic unbiased approach to identifying culprit drugs. Using the RegiSCAR database and algorithm for drug causality for epidermal necrolysis to analyze the cohort, more than half of causative agents were determined to be different from those initially identified by the treating physicians. Nine additional suspected culprit drugs were identified, while 43 drugs initially identified as allergens were exonerated.⁶

Etiology-associated definitions for blistering reactions in children have been proposed to replace the existing terms Stevens-Johnson syndrome, toxic epidermal necrolysis, and others.⁷ Investigators in a recent study reclassified cases of SJS and TEN as reactive infectious mucocutaneous eruption (RIME) or drug-induced epidermal necrolysis (DEN), respectively. In RIME cases, Mycoplasma pneumoniae was the most commonly identified trigger, and in DEN cases, anticonvulsants were the most common class of culprit medications. Cases of RIME were less severe and were most often treated with antibiotics, whereas patients with DEN were more likely to receive supportive care, corticosteroids, intravenous immunoglobulins, and other immunosuppressive therapies.⁷

In addition to causing acute devastating mucocutaneous complications, SJS and TEN have long-lasting effects that require ongoing care. In a cohort of 6552 incident SJS/TEN cases over an 11-year period, survivors of SJS/TEN endured a mean loss of 9.4 years in life expectancy and excess health care expenditures of $3752 per year compared with age- and sex-matched controls. Patients with more severe disease, comorbid malignancy, diabetes, end-stage renal disease, or SJS/TEN sequelae experienced greater loss in life expectancy and lifetime health care expenditures.⁸ Separately, a qualitative study investigating the psychological impact of SJS/TEN in pediatric patients described sequelae including night terrors, posttraumatic stress disorder, depression, and anxiety for many years after the acute phase. Many patients reported a desire for increased support for their physical and emotional needs following hospital discharge.⁹

Skin and Soft Tissue Infections: Diagnosis, Management, and Prevention

Dermatology consultation has been shown to be a cost-effective intervention to improve outcomes in hospitalized patients with skin and soft tissue infections.^10,11 In particular, cellulitis frequently is misdiagnosed, leading to unnecessary antibiotic use, hospitalizations, and major health care expenditures.¹² Recognizing this challenge, researchers have worked to develop objective tools to improve diagnostic accuracy. In a large prospective prognostic validation study, Pulia et al¹³ found that thermal imaging alone or in combination with the ALT-70 prediction model (asymmetry, leukocytosis, tachycardia, and age ≥70 years) could be used successfully to reduce overdiagnosis of cellulitis. Both thermal imaging and the ALT-70 prediction model demonstrated robust sensitivity (93.5% and 98.8%, respectively) but low specificity (38.4% and 22.0%, respectively, and 53.9% when combined).¹³

In a systematic review, Kovacs et al¹⁴ analyzed case reports of pseudocellulitis caused by chemotherapeutic medications. Of the 81 cases selected, 58 (71.6%) were associated with gemcitabine, with the remaining 23 (28.4%) attributed to pemetrexed. Within this group, two-thirds of the patients received antibiotic treatment prior to receiving the correct diagnosis, and 36% experienced interruptions to their oncologic therapies. In contrast to infectious cellulitis, which tends to be unilateral and associated with elevated erythrocyte sedimentation rate or C-reactive protein, most chemotherapy-induced pseudocellulitis cases occurred bilaterally on the lower extremities, while erythrocyte sedimentation rate and C-reactive protein seldom were elevated.¹⁴

Necrotizing soft tissue infections (NSTIs) are severe life-threatening conditions characterized by widespread tissue destruction, signs of systemic toxicity, hemodynamic collapse, organ failure, and high mortality. Surgical inspection along with intraoperative tissue culture is the gold standard for diagnosis. Early detection, prompt surgical intervention, and appropriate antibiotic treatment are essential to reduce mortality and improve outcomes.¹⁵ A retrospective study of patients with surgically confirmed NSTIs assessed the incidence and risk factors for recurrence within 1 year following an initial NSTI of the lower extremity. Among 93 included patients, 32 (34.4%) had recurrence within 1 year, and more than half of recurrences occurred in the first 3 months (median, 66 days). The comparison of patients with and without recurrence showed similar proportions of antibiotic prophylaxis use after the first NSTI. There was significantly less compression therapy use (33.3% vs 62.3%; P=.13) and more negative pressure wound therapy use (83.3% vs 63.3%; P=.03) in the recurrence group, though the authors acknowledged that factors such as severity of pain and size of soft tissue defect may have affected the decisions for compression and negative pressure wound therapy.¹⁶

Residents of nursing homes are a particularly vulnerable population at high risk for health care–associated infections due to older age and a higher likelihood of having wounds, indwelling medical devices, and/or coexisting conditions.¹⁷ One cluster-randomized trial compared universal decolonization with routine-care bathing practices in nursing homes (N=28,956 residents). Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. Transfer to a hospital due to infection decreased from 62.9% to 52.2% with decolonization, for a difference in risk ratio of 16.6% (P<.001) compared with routine care. Additionally, the difference in risk ratio of the secondary end point (transfer to a hospital for any reason) was 14.6%. The number needed to treat was 9.7 to prevent 1 infection-related hospitalization and 8.9 to prevent 1 hospitalization for any reason.¹⁷

Autoimmune Blistering Diseases

Although rare, AIBDs are potentially life-threatening cutaneous diseases that often require inpatient management. While corticosteroids remain the mainstay of initial AIBD management, rituximab is now well recognized as the steroid-sparing treatment of choice for patients with moderate to severe pemphigus. In a long-term follow-up study of Ritux 3¹⁸—the trial that led to the US Food and Drug Administration approval of rituximab in the treatment of moderate to severe pemphigus vulgaris—researchers assessed the long-term efficacy and safety of rituximab as a first-line treatment in patients with pemphigus.¹⁹ The 5- and 7-year disease-free survival rates without corticosteroid therapy for patients treated with rituximab were 76.7% and 72.1%, respectively, compared with 35.3% and 35.3% in those treated with prednisone alone (P<.001). Fewer serious adverse events were reported in those treated with rituximab plus prednisone compared with those treated with prednisone alone. None of the patients who maintained complete remission off corticosteroid therapy received any additional maintenance infusions of rituximab after the end of the Ritux 3 regimen (1 g of rituximab at day 0 and day 14, then 500 mg at months 12 and 18).¹⁹

By contrast, treatment of severe bullous pemphigoid (BP) often is less clear-cut, as no single therapeutic option has been shown to be superior to other immunomodulatory and immunosuppressive regimens, and the medical comorbidities of elderly patients with BP can be limiting. Fortunately, newer therapies with favorable safety profiles have emerged in recent years. In a multicenter retrospective study, 100 patients with BP received omalizumab after previously failing to respond to at least one alternative therapy. Disease control was obtained after a median of 10 days, and complete remission was achieved in 77% of patients in a median time of 3 months.²⁰ In a multicenter retrospective cohort study of 146 patients with BP treated with dupilumab following the atopic dermatitis dosing schedule (one 600-mg dose followed by 300 mg every 2 weeks), disease control was achieved in a median of 14 days, while complete remission was achieved in 35.6% of patients, with 8.9% relapsing during the observation period.²¹ A retrospective case series of 30 patients with BP treated with dupilumab with maintenance dosing frequency tailored to individual patient response showed complete remission or marked response in 76.7% (23/30) of patients.²² A phase 2/3 randomized controlled trial of dupilumab in BP is currently ongoing (ClinicalTrials.gov identifier NCT04206553).

Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis of pregnancy that may be difficult to distinguish clinically from polymorphic eruption of pregnancy but confers notably different maternal and fetal risks. Researchers developed and validated a scoring system using clinical factors—history of pemphigoid gestationis, primigravidae, timing of rash onset, and specific clinical examination findings—that was able to differentiate between the 2 diseases with 79% sensitivity, 95% specificity, and an area under the curve of 0.93 without the need for advanced immunologic testing.²³

Final Thoughts

Highlights of the literature from 2023-2024 demonstrate advancements in hospital-based dermatology as well as ongoing challenges. This year’s review emphasizes key developments in severe cutaneous adverse drug reactions, skin and soft tissue infections, and AIBDs. Continued expansion of knowledge in these areas and others informs patient care and demonstrates the value of dermatologic expertise in the inpatient setting.

Inpatient consultative dermatology has advanced as a subspecialty and increasingly gained recognition in recent years. Since its founding in 2009, the Society of Dermatology Hospitalists has fostered research and education in hospital dermatology. Last year, we reviewed the 2022-2023 literature with a focus on developments in severe cutaneous adverse reactions, supportive oncodermatology, cost of inpatient services, and teledermatology.¹ In this review, we highlight 3 areas of interest from the 2023-2024 literature: severe cutaneous adverse drug reactions, skin and soft tissue infections, and autoimmune blistering diseases (AIBDs).

Severe Cutaneous Adverse Drug Reactions

Adverse drug reactions are among the most common diagnoses encountered by inpatient dermatology consultants.^2,3 Severe cutaneous adverse drug reactions are associated with substantial morbidity and mortality. Efforts to characterize these conditions and standardize their diagnosis and management continue to be a major focus of ongoing research.

A single-center retrospective analysis of 102 cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome evaluated differences in clinical manifestations depending on the culprit drug, offering insights into the heterogeneity of DRESS syndrome and the potential for diagnostic uncertainty.⁴ The shortest median latency was observed in a case caused by penicillin and cephalosporins (12 and 18 days, respectively), while DRESS syndrome secondary to allopurinol had the longest median latency (36 days). Nonsteroidal anti-inflammatory drug–induced DRESS syndrome was associated with the shortest hospital stay (6.5 days), while cephalosporin and vancomycin cases had the highest mortality rates.⁴

In the first international Delphi consensus study on the diagnostic workup, severity assessment, and management of DRESS syndrome, 54 dermatology and/or allergy experts reached consensus on 93 statements.⁵ Specific recommendations included basic evaluation with complete blood count with differential, kidney and liver function parameters, and electrocardiogram for all patients with suspected DRESS syndrome, with additional complementary workup considered in patients with evidence of specific organ damage and/or severe disease. In the proposed DRESS syndrome severity grading scheme, laboratory values that reached consensus for inclusion were hemoglobin, neutrophil, and platelet counts and creatinine, transaminases, and alkaline phosphatase levels. Although treatment of DRESS syndrome should be based on assessed disease severity, treatment with corticosteroids should be initiated in all patients with confirmed DRESS syndrome. Cyclosporine, antibodies interfering with the IL-5 axis, and intravenous immunoglobulins can be considered in patients with corticosteroid-refractory DRESS syndrome, and antiviral treatment can be considered in patients with a high serum cytomegalovirus viral load. Regularly following up with laboratory evaluation of involved organs; screening for autoantibodies, thyroid dysfunction, and steroid adverse effects; and offering of psychological support also were consensus recommendations.⁵

Identifying causative agents in drug hypersensitivity reactions remains challenging. A retrospective cohort study of 48 patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) highlighted the need for a systematic unbiased approach to identifying culprit drugs. Using the RegiSCAR database and algorithm for drug causality for epidermal necrolysis to analyze the cohort, more than half of causative agents were determined to be different from those initially identified by the treating physicians. Nine additional suspected culprit drugs were identified, while 43 drugs initially identified as allergens were exonerated.⁶

Etiology-associated definitions for blistering reactions in children have been proposed to replace the existing terms Stevens-Johnson syndrome, toxic epidermal necrolysis, and others.⁷ Investigators in a recent study reclassified cases of SJS and TEN as reactive infectious mucocutaneous eruption (RIME) or drug-induced epidermal necrolysis (DEN), respectively. In RIME cases, Mycoplasma pneumoniae was the most commonly identified trigger, and in DEN cases, anticonvulsants were the most common class of culprit medications. Cases of RIME were less severe and were most often treated with antibiotics, whereas patients with DEN were more likely to receive supportive care, corticosteroids, intravenous immunoglobulins, and other immunosuppressive therapies.⁷

In addition to causing acute devastating mucocutaneous complications, SJS and TEN have long-lasting effects that require ongoing care. In a cohort of 6552 incident SJS/TEN cases over an 11-year period, survivors of SJS/TEN endured a mean loss of 9.4 years in life expectancy and excess health care expenditures of $3752 per year compared with age- and sex-matched controls. Patients with more severe disease, comorbid malignancy, diabetes, end-stage renal disease, or SJS/TEN sequelae experienced greater loss in life expectancy and lifetime health care expenditures.⁸ Separately, a qualitative study investigating the psychological impact of SJS/TEN in pediatric patients described sequelae including night terrors, posttraumatic stress disorder, depression, and anxiety for many years after the acute phase. Many patients reported a desire for increased support for their physical and emotional needs following hospital discharge.⁹

Skin and Soft Tissue Infections: Diagnosis, Management, and Prevention

Dermatology consultation has been shown to be a cost-effective intervention to improve outcomes in hospitalized patients with skin and soft tissue infections.^10,11 In particular, cellulitis frequently is misdiagnosed, leading to unnecessary antibiotic use, hospitalizations, and major health care expenditures.¹² Recognizing this challenge, researchers have worked to develop objective tools to improve diagnostic accuracy. In a large prospective prognostic validation study, Pulia et al¹³ found that thermal imaging alone or in combination with the ALT-70 prediction model (asymmetry, leukocytosis, tachycardia, and age ≥70 years) could be used successfully to reduce overdiagnosis of cellulitis. Both thermal imaging and the ALT-70 prediction model demonstrated robust sensitivity (93.5% and 98.8%, respectively) but low specificity (38.4% and 22.0%, respectively, and 53.9% when combined).¹³

In a systematic review, Kovacs et al¹⁴ analyzed case reports of pseudocellulitis caused by chemotherapeutic medications. Of the 81 cases selected, 58 (71.6%) were associated with gemcitabine, with the remaining 23 (28.4%) attributed to pemetrexed. Within this group, two-thirds of the patients received antibiotic treatment prior to receiving the correct diagnosis, and 36% experienced interruptions to their oncologic therapies. In contrast to infectious cellulitis, which tends to be unilateral and associated with elevated erythrocyte sedimentation rate or C-reactive protein, most chemotherapy-induced pseudocellulitis cases occurred bilaterally on the lower extremities, while erythrocyte sedimentation rate and C-reactive protein seldom were elevated.¹⁴

Necrotizing soft tissue infections (NSTIs) are severe life-threatening conditions characterized by widespread tissue destruction, signs of systemic toxicity, hemodynamic collapse, organ failure, and high mortality. Surgical inspection along with intraoperative tissue culture is the gold standard for diagnosis. Early detection, prompt surgical intervention, and appropriate antibiotic treatment are essential to reduce mortality and improve outcomes.¹⁵ A retrospective study of patients with surgically confirmed NSTIs assessed the incidence and risk factors for recurrence within 1 year following an initial NSTI of the lower extremity. Among 93 included patients, 32 (34.4%) had recurrence within 1 year, and more than half of recurrences occurred in the first 3 months (median, 66 days). The comparison of patients with and without recurrence showed similar proportions of antibiotic prophylaxis use after the first NSTI. There was significantly less compression therapy use (33.3% vs 62.3%; P=.13) and more negative pressure wound therapy use (83.3% vs 63.3%; P=.03) in the recurrence group, though the authors acknowledged that factors such as severity of pain and size of soft tissue defect may have affected the decisions for compression and negative pressure wound therapy.¹⁶

Residents of nursing homes are a particularly vulnerable population at high risk for health care–associated infections due to older age and a higher likelihood of having wounds, indwelling medical devices, and/or coexisting conditions.¹⁷ One cluster-randomized trial compared universal decolonization with routine-care bathing practices in nursing homes (N=28,956 residents). Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. Transfer to a hospital due to infection decreased from 62.9% to 52.2% with decolonization, for a difference in risk ratio of 16.6% (P<.001) compared with routine care. Additionally, the difference in risk ratio of the secondary end point (transfer to a hospital for any reason) was 14.6%. The number needed to treat was 9.7 to prevent 1 infection-related hospitalization and 8.9 to prevent 1 hospitalization for any reason.¹⁷

Autoimmune Blistering Diseases

Although rare, AIBDs are potentially life-threatening cutaneous diseases that often require inpatient management. While corticosteroids remain the mainstay of initial AIBD management, rituximab is now well recognized as the steroid-sparing treatment of choice for patients with moderate to severe pemphigus. In a long-term follow-up study of Ritux 3¹⁸—the trial that led to the US Food and Drug Administration approval of rituximab in the treatment of moderate to severe pemphigus vulgaris—researchers assessed the long-term efficacy and safety of rituximab as a first-line treatment in patients with pemphigus.¹⁹ The 5- and 7-year disease-free survival rates without corticosteroid therapy for patients treated with rituximab were 76.7% and 72.1%, respectively, compared with 35.3% and 35.3% in those treated with prednisone alone (P<.001). Fewer serious adverse events were reported in those treated with rituximab plus prednisone compared with those treated with prednisone alone. None of the patients who maintained complete remission off corticosteroid therapy received any additional maintenance infusions of rituximab after the end of the Ritux 3 regimen (1 g of rituximab at day 0 and day 14, then 500 mg at months 12 and 18).¹⁹

By contrast, treatment of severe bullous pemphigoid (BP) often is less clear-cut, as no single therapeutic option has been shown to be superior to other immunomodulatory and immunosuppressive regimens, and the medical comorbidities of elderly patients with BP can be limiting. Fortunately, newer therapies with favorable safety profiles have emerged in recent years. In a multicenter retrospective study, 100 patients with BP received omalizumab after previously failing to respond to at least one alternative therapy. Disease control was obtained after a median of 10 days, and complete remission was achieved in 77% of patients in a median time of 3 months.²⁰ In a multicenter retrospective cohort study of 146 patients with BP treated with dupilumab following the atopic dermatitis dosing schedule (one 600-mg dose followed by 300 mg every 2 weeks), disease control was achieved in a median of 14 days, while complete remission was achieved in 35.6% of patients, with 8.9% relapsing during the observation period.²¹ A retrospective case series of 30 patients with BP treated with dupilumab with maintenance dosing frequency tailored to individual patient response showed complete remission or marked response in 76.7% (23/30) of patients.²² A phase 2/3 randomized controlled trial of dupilumab in BP is currently ongoing (ClinicalTrials.gov identifier NCT04206553).

Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis of pregnancy that may be difficult to distinguish clinically from polymorphic eruption of pregnancy but confers notably different maternal and fetal risks. Researchers developed and validated a scoring system using clinical factors—history of pemphigoid gestationis, primigravidae, timing of rash onset, and specific clinical examination findings—that was able to differentiate between the 2 diseases with 79% sensitivity, 95% specificity, and an area under the curve of 0.93 without the need for advanced immunologic testing.²³

Final Thoughts

Highlights of the literature from 2023-2024 demonstrate advancements in hospital-based dermatology as well as ongoing challenges. This year’s review emphasizes key developments in severe cutaneous adverse drug reactions, skin and soft tissue infections, and AIBDs. Continued expansion of knowledge in these areas and others informs patient care and demonstrates the value of dermatologic expertise in the inpatient setting.

Inpatient consultative dermatology has advanced as a subspecialty and increasingly gained recognition in recent years. Since its founding in 2009, the Society of Dermatology Hospitalists has fostered research and education in hospital dermatology. Last year, we reviewed the 2022-2023 literature with a focus on developments in severe cutaneous adverse reactions, supportive oncodermatology, cost of inpatient services, and teledermatology.¹ In this review, we highlight 3 areas of interest from the 2023-2024 literature: severe cutaneous adverse drug reactions, skin and soft tissue infections, and autoimmune blistering diseases (AIBDs).

Severe Cutaneous Adverse Drug Reactions

Adverse drug reactions are among the most common diagnoses encountered by inpatient dermatology consultants.^2,3 Severe cutaneous adverse drug reactions are associated with substantial morbidity and mortality. Efforts to characterize these conditions and standardize their diagnosis and management continue to be a major focus of ongoing research.

A single-center retrospective analysis of 102 cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome evaluated differences in clinical manifestations depending on the culprit drug, offering insights into the heterogeneity of DRESS syndrome and the potential for diagnostic uncertainty.⁴ The shortest median latency was observed in a case caused by penicillin and cephalosporins (12 and 18 days, respectively), while DRESS syndrome secondary to allopurinol had the longest median latency (36 days). Nonsteroidal anti-inflammatory drug–induced DRESS syndrome was associated with the shortest hospital stay (6.5 days), while cephalosporin and vancomycin cases had the highest mortality rates.⁴

In the first international Delphi consensus study on the diagnostic workup, severity assessment, and management of DRESS syndrome, 54 dermatology and/or allergy experts reached consensus on 93 statements.⁵ Specific recommendations included basic evaluation with complete blood count with differential, kidney and liver function parameters, and electrocardiogram for all patients with suspected DRESS syndrome, with additional complementary workup considered in patients with evidence of specific organ damage and/or severe disease. In the proposed DRESS syndrome severity grading scheme, laboratory values that reached consensus for inclusion were hemoglobin, neutrophil, and platelet counts and creatinine, transaminases, and alkaline phosphatase levels. Although treatment of DRESS syndrome should be based on assessed disease severity, treatment with corticosteroids should be initiated in all patients with confirmed DRESS syndrome. Cyclosporine, antibodies interfering with the IL-5 axis, and intravenous immunoglobulins can be considered in patients with corticosteroid-refractory DRESS syndrome, and antiviral treatment can be considered in patients with a high serum cytomegalovirus viral load. Regularly following up with laboratory evaluation of involved organs; screening for autoantibodies, thyroid dysfunction, and steroid adverse effects; and offering of psychological support also were consensus recommendations.⁵

Identifying causative agents in drug hypersensitivity reactions remains challenging. A retrospective cohort study of 48 patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) highlighted the need for a systematic unbiased approach to identifying culprit drugs. Using the RegiSCAR database and algorithm for drug causality for epidermal necrolysis to analyze the cohort, more than half of causative agents were determined to be different from those initially identified by the treating physicians. Nine additional suspected culprit drugs were identified, while 43 drugs initially identified as allergens were exonerated.⁶

Etiology-associated definitions for blistering reactions in children have been proposed to replace the existing terms Stevens-Johnson syndrome, toxic epidermal necrolysis, and others.⁷ Investigators in a recent study reclassified cases of SJS and TEN as reactive infectious mucocutaneous eruption (RIME) or drug-induced epidermal necrolysis (DEN), respectively. In RIME cases, Mycoplasma pneumoniae was the most commonly identified trigger, and in DEN cases, anticonvulsants were the most common class of culprit medications. Cases of RIME were less severe and were most often treated with antibiotics, whereas patients with DEN were more likely to receive supportive care, corticosteroids, intravenous immunoglobulins, and other immunosuppressive therapies.⁷

In addition to causing acute devastating mucocutaneous complications, SJS and TEN have long-lasting effects that require ongoing care. In a cohort of 6552 incident SJS/TEN cases over an 11-year period, survivors of SJS/TEN endured a mean loss of 9.4 years in life expectancy and excess health care expenditures of $3752 per year compared with age- and sex-matched controls. Patients with more severe disease, comorbid malignancy, diabetes, end-stage renal disease, or SJS/TEN sequelae experienced greater loss in life expectancy and lifetime health care expenditures.⁸ Separately, a qualitative study investigating the psychological impact of SJS/TEN in pediatric patients described sequelae including night terrors, posttraumatic stress disorder, depression, and anxiety for many years after the acute phase. Many patients reported a desire for increased support for their physical and emotional needs following hospital discharge.⁹

Skin and Soft Tissue Infections: Diagnosis, Management, and Prevention

Dermatology consultation has been shown to be a cost-effective intervention to improve outcomes in hospitalized patients with skin and soft tissue infections.^10,11 In particular, cellulitis frequently is misdiagnosed, leading to unnecessary antibiotic use, hospitalizations, and major health care expenditures.¹² Recognizing this challenge, researchers have worked to develop objective tools to improve diagnostic accuracy. In a large prospective prognostic validation study, Pulia et al¹³ found that thermal imaging alone or in combination with the ALT-70 prediction model (asymmetry, leukocytosis, tachycardia, and age ≥70 years) could be used successfully to reduce overdiagnosis of cellulitis. Both thermal imaging and the ALT-70 prediction model demonstrated robust sensitivity (93.5% and 98.8%, respectively) but low specificity (38.4% and 22.0%, respectively, and 53.9% when combined).¹³

In a systematic review, Kovacs et al¹⁴ analyzed case reports of pseudocellulitis caused by chemotherapeutic medications. Of the 81 cases selected, 58 (71.6%) were associated with gemcitabine, with the remaining 23 (28.4%) attributed to pemetrexed. Within this group, two-thirds of the patients received antibiotic treatment prior to receiving the correct diagnosis, and 36% experienced interruptions to their oncologic therapies. In contrast to infectious cellulitis, which tends to be unilateral and associated with elevated erythrocyte sedimentation rate or C-reactive protein, most chemotherapy-induced pseudocellulitis cases occurred bilaterally on the lower extremities, while erythrocyte sedimentation rate and C-reactive protein seldom were elevated.¹⁴

Necrotizing soft tissue infections (NSTIs) are severe life-threatening conditions characterized by widespread tissue destruction, signs of systemic toxicity, hemodynamic collapse, organ failure, and high mortality. Surgical inspection along with intraoperative tissue culture is the gold standard for diagnosis. Early detection, prompt surgical intervention, and appropriate antibiotic treatment are essential to reduce mortality and improve outcomes.¹⁵ A retrospective study of patients with surgically confirmed NSTIs assessed the incidence and risk factors for recurrence within 1 year following an initial NSTI of the lower extremity. Among 93 included patients, 32 (34.4%) had recurrence within 1 year, and more than half of recurrences occurred in the first 3 months (median, 66 days). The comparison of patients with and without recurrence showed similar proportions of antibiotic prophylaxis use after the first NSTI. There was significantly less compression therapy use (33.3% vs 62.3%; P=.13) and more negative pressure wound therapy use (83.3% vs 63.3%; P=.03) in the recurrence group, though the authors acknowledged that factors such as severity of pain and size of soft tissue defect may have affected the decisions for compression and negative pressure wound therapy.¹⁶

Residents of nursing homes are a particularly vulnerable population at high risk for health care–associated infections due to older age and a higher likelihood of having wounds, indwelling medical devices, and/or coexisting conditions.¹⁷ One cluster-randomized trial compared universal decolonization with routine-care bathing practices in nursing homes (N=28,956 residents). Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. Transfer to a hospital due to infection decreased from 62.9% to 52.2% with decolonization, for a difference in risk ratio of 16.6% (P<.001) compared with routine care. Additionally, the difference in risk ratio of the secondary end point (transfer to a hospital for any reason) was 14.6%. The number needed to treat was 9.7 to prevent 1 infection-related hospitalization and 8.9 to prevent 1 hospitalization for any reason.¹⁷

Autoimmune Blistering Diseases

Although rare, AIBDs are potentially life-threatening cutaneous diseases that often require inpatient management. While corticosteroids remain the mainstay of initial AIBD management, rituximab is now well recognized as the steroid-sparing treatment of choice for patients with moderate to severe pemphigus. In a long-term follow-up study of Ritux 3¹⁸—the trial that led to the US Food and Drug Administration approval of rituximab in the treatment of moderate to severe pemphigus vulgaris—researchers assessed the long-term efficacy and safety of rituximab as a first-line treatment in patients with pemphigus.¹⁹ The 5- and 7-year disease-free survival rates without corticosteroid therapy for patients treated with rituximab were 76.7% and 72.1%, respectively, compared with 35.3% and 35.3% in those treated with prednisone alone (P<.001). Fewer serious adverse events were reported in those treated with rituximab plus prednisone compared with those treated with prednisone alone. None of the patients who maintained complete remission off corticosteroid therapy received any additional maintenance infusions of rituximab after the end of the Ritux 3 regimen (1 g of rituximab at day 0 and day 14, then 500 mg at months 12 and 18).¹⁹

By contrast, treatment of severe bullous pemphigoid (BP) often is less clear-cut, as no single therapeutic option has been shown to be superior to other immunomodulatory and immunosuppressive regimens, and the medical comorbidities of elderly patients with BP can be limiting. Fortunately, newer therapies with favorable safety profiles have emerged in recent years. In a multicenter retrospective study, 100 patients with BP received omalizumab after previously failing to respond to at least one alternative therapy. Disease control was obtained after a median of 10 days, and complete remission was achieved in 77% of patients in a median time of 3 months.²⁰ In a multicenter retrospective cohort study of 146 patients with BP treated with dupilumab following the atopic dermatitis dosing schedule (one 600-mg dose followed by 300 mg every 2 weeks), disease control was achieved in a median of 14 days, while complete remission was achieved in 35.6% of patients, with 8.9% relapsing during the observation period.²¹ A retrospective case series of 30 patients with BP treated with dupilumab with maintenance dosing frequency tailored to individual patient response showed complete remission or marked response in 76.7% (23/30) of patients.²² A phase 2/3 randomized controlled trial of dupilumab in BP is currently ongoing (ClinicalTrials.gov identifier NCT04206553).

Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis of pregnancy that may be difficult to distinguish clinically from polymorphic eruption of pregnancy but confers notably different maternal and fetal risks. Researchers developed and validated a scoring system using clinical factors—history of pemphigoid gestationis, primigravidae, timing of rash onset, and specific clinical examination findings—that was able to differentiate between the 2 diseases with 79% sensitivity, 95% specificity, and an area under the curve of 0.93 without the need for advanced immunologic testing.²³

Final Thoughts

Highlights of the literature from 2023-2024 demonstrate advancements in hospital-based dermatology as well as ongoing challenges. This year’s review emphasizes key developments in severe cutaneous adverse drug reactions, skin and soft tissue infections, and AIBDs. Continued expansion of knowledge in these areas and others informs patient care and demonstrates the value of dermatologic expertise in the inpatient setting.

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

Keloids are fibroproliferative lesions caused by aberrant wound healing in predisposed individuals.¹ While keloids have been reported in patients of all races and ethnicities, they most commonly develop in individuals of African or Asian descent.² Often associated with symptoms such as pain and itching, keloids can be disfiguring and result in poorer quality of life.³ There is a paucity of research on keloid pathogenesis and efficacious therapeutics, particularly in patients with skin of color (SOC). Herein, we outline the current research on keloid treatment and highlight promising new therapies ranging from innovative intralesional techniques to advanced laser-based and biologic therapies.

Deficiencies in Skin of Color Research

Although keloids are 17 times more prevalent in patients with SOC,⁴ there is a considerable lack of focus on this population in the literature.⁵ Studies on keloids that include individuals with SOC often group patients of all skin types together, and subgroup analyses are not always performed.^6,7 As a result, dermatologists may face considerable challenges in providing effective treatments for keloids in patients with SOC. With few evidence-based options available, patients with SOC who have keloids continue to experience impairments in quality of life.

Common Keloid Therapies

There currently is no gold-standard treatment for keloids. Common therapeutic modalities include intralesional corticosteroids (ILCs), antineoplastic agents and neuromodulators, laser-based devices, and surgical therapies (eg, excision), as well as combined medical and surgical techniques.⁸

Intralesional Corticosteroids—Minimally invasive ILCs are the first-line treatment in all patients with keloids, regardless of skin phototype. Because keloid formation results from trauma to the skin, ILCs often are recommended to minimize further skin damage.⁵ One meta-analysis found that ILCs have demonstrated success rates of 50% to 100%⁹; however, these studies frequently combine ILCs with other treatment modalities, and few studies have focused on the efficacy of ILC monotherapy in patients with SOC.^6,10-13

Antineoplastic Agents and Neuromodulators—Certain antineoplastic agents (eg, 5-fluorouracil [5-FU] and bleomycin) and neuromodulators (eg, botulinum toxin A [BTA]) also have been studied in keloid management.⁸

5-Fluorouracil frequently is combined with ILCs such as triamcinolone (TAC). Combined therapy is more effective than TAC monotherapy in scar height reduction.^14,15 Rates of adverse events such as dyspigmentation, atrophy, and telangiectasias also were lower in patients who received combined therapy.^14,15 A systematic review found that intralesional bleomycin may be more effective than TAC alone, 5-FU alone, TAC combined with 5-FU, and TAC combined with cryotherapy; however, hyperpigmentation was a common adverse event, occurring in roughly 70% (42/60) of patients.^16,17 Additionally, a 2024 meta-analysis evaluated 20 randomized controlled trials comprising 1114 patients treated with intralesional TAC, 5-FU, BTA, verapamil, and/or bleomycin. Botulinum toxin A and TAC plus 5-FU were found to have outstanding therapeutic efficacy for keloids, and rates of adverse events were similar among users of TAC, 5-FU, BTA, and TAC plus 5-FU.¹⁸

While antineoplastic agents and BTA may be promising keloid therapies, further studies demonstrating their efficacy and safety profiles are necessary, particularly regarding dyspigmentation as a potential adverse event, as this may be of concern in patients with darker phototypes.

Laser Therapies—Of all treatment modalities, laser-based keloid therapies have been the most robustly studied in SOC. The 2 main types are ablative (eg, CO₂, Er:YAG) and nonablative (eg, pulsed dye, Nd:YAG) lasers. Ablative lasers rapidly heat water molecules within the skin, thereby vaporizing the skin cells in a controlled precise process that reduces scar tissue by removing layers of skin. Nonablative lasers target hemoglobin in blood vessels, reducing oxygen supply and inducing collagen remodeling without damaging the epidermis.¹⁹

For patients with SOC, lasers carry a risk for postinflammatory hyperpigmentation.²⁰ To address this risk, recent advancements in laser technology and procedural protocols have aimed to minimize the number of passes and utilize cooling devices²¹; however, many of these recommendations are based on retrospective reviews and small case series. A 2024 meta-analysis comprising 550 patients found that the combination of fractional CO₂ laser therapy and 5-FU was the most effective intervention, markedly reducing Vancouver Scar Scale and pliability scores as well as keloid thickness.²² Conversely, pulsed dye lasers were the least effective in terms of improving scar thickness, pigmentation, and pliability when compared to other treatments.

Randomized controlled trials of laser-based therapies in patients with SOC are lacking in the literature. Future studies should focus on calibrating laser-based therapies for those with darker skin tones and examine the efficacy and adverse effects of ablative and nonablative lasers in patients with SOC.

Promising New Keloid Therapies

Keloid disease pathogenesis is incompletely understood, but several new therapeutic targets have been highlighted in the literature, including dupilumab, pentoxifylline, sirtuin 6 (SIRT6) modulators, remdesivir, and needle-assisted electrocoagulation plus pharmacotherapy.

Dupilumab—An anti–IL-4 and IL-13 monoclonal antibody, dupilumab was first approved for the treatment of severe atopic dermatitis. Its use has broadened since its approval, and keloids have been identified as a potential therapeutic target. A 2019 case study described a 53-year-old Black man with severe atopic dermatitis and chronic keloids that regressed with systemic dupilumab therapy.²³ This prompted a follow-up case-control study using real-time polymerase chain reaction testing to evaluate Th2 gene expression (IL-4R, IL-13, and CCL18) of lesional and nonlesional tissue in 3 Black patients with chronic keloids and no concurrent atopic dermatitis vs 5 healthy Black controls.Despite the limited sample size, a significant increase in IL-13 and the Th2 chemokine CCL18 was found in patients with keloids compared to controls (P<.05), suggesting that the entire integument of patients with severe keloids is abnormal.²³ This finding supports the use of systemic treatments for chronic and multifocal keloid disease. Several subsequent case reports have corroborated the efficacy of systemic and/or intralesional dupilumab.^24,25 However, some studies have reported contradictory findings, suggesting the need for high-quality clinical trials.^26,27

Pentoxifylline—Pentoxifylline is a methylated xanthine derivative and a nonspecific phosphodiesterase ­inhibitor used to treat claudication from peripheral artery disease. It also inhibits the proliferation and rate of collagen synthesis of fibroblasts from keloids in vitro.^28,29 A 2019 retrospective, open-label pilot study analyzed postsurgical keloid recurrence in 45 patients with 67 unique keloids that were stratified into low- and high-risk groups based on clinical factors including multiple symptomatic keloids, history of recurrence, and family history.³⁰ Both the low- and the high-risk groups were treated with 40 mg/mL intralesional triamcinolone acetonide monthly for 6 months; however, some of the high-risk keloids also received pentoxifylline 300 mg 3 times daily for 6 months. There was a statistically significant decrease in keloid recurrence rate between the high-risk group treated with pentoxifylline and the low-risk group for whom pentoxifylline was not prescribed (P=.015).

Similarly, a randomized clinical trial comparing the efficacy of combination intralesional pentoxifylline and intralesional triamcinolone vs monotherapy with pentoxifylline or triamcinolone found the most significant improvement in the combination cohort with reduction in keloid height (P=.04), pliability (P=.003), and vascularity (P=.05).³¹ These findings highlight the need for supplementary studies on the use of pentoxifylline for keloid therapy.

SIRT6 Modulators—SIRT6 modulators are an exciting future therapeutic target. In a recent case-control study evaluating the histologic milieu of keloid tissue vs normal skin specimens, the researchers found that selective overexpression of SIRT6 via the use of a recombinant adenovirus in keloid fibroblasts attenuated proliferation, invasion, and collagen synthesis while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity.³²

Remdesivir—The antiviral drug remdesivir has been reported to have pharmacologic activities in a wide range of fibrotic diseases, including keloids. A 2024 study explored the potential effect and mechanisms of remdesivir on skin fibrosis both in vitro and in rodents.³³ Remdesivir was found to decrease skin fibrosis and attenuate the gross weight of keloid tissues in vivo, suppress fibroblast activation and autophagy both in vivo and in vitro, dampen fibroblast activation by the TGF-β1/Smad signaling pathway, and inhibit fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. These results demonstrate the therapeutic potential of remdesivir for keloid management.

Needle-Assisted Electrocoagulation Plus Pharmacotherapy—A novel needle-assisted electrocoagulation technique combined with pharmacotherapy (corticosteroid and 5-FU injections) was effective in a Chinese clinical trial involving 6 patients with keloids.³⁴ Investigators used Vancouver Scar Scale and both Patient and Observer Scar Assessment Scale scores to grade patients’ scars before treatment and 1 month after the first treatment cycle. They found that ablation combined with pharmacotherapy significantly reduced all 3 scores without any obvious adverse events (P=.004, P=.006, and P=.017, respectively). This novel combination treatment may serve as a safe and effective therapeutic approach for keloid removal.

Final Thoughts

Emerging treatments offer promising new horizons in keloid management; however, the lack of robust, high-quality clinical trials, especially those focusing on SOC, underscores a pressing need for comprehensive and inclusive studies. There is much work to be done to close the existing knowledge gap, and future studies must be more intentional with recruitment, assuring that the patients who are disproportionately affected by these lesions are represented in study populations.

The American Contact Dermatitis Society (ACDS) selected sulfites as the 2024 Allergen of the Year.¹ Due to their preservative and antioxidant properties, sulfites are prevalent in a variety of foods, beverages, medications, and personal care products; however, sulfites also have been implicated as a potential contact allergen. In this article, we review common sources of sulfite exposure, clinical manifestations of allergic contact dermatitis (ACD) to sulfites, and patch testing considerations for this emerging allergen.

What Are Sulfites?

Sulfiting agents are compounds that contain the sulfite ion SO₃^2-, including sulfur dioxide, sodium disulfite (sodium metabisulfite), and potassium metabisulfite.² Sulfites occur naturally in the environment and commonly are used as preservatives, antibrowning agents, and antioxidants in various foods, beverages, medications, cosmetics, and skin care products. As antibrowning agents and antioxidants, sulfites help maintain the natural appearance of foods and other products and prevent premature spoiling by inactivating oxidative enzymes.³ It should be noted that sulfites and sulfates are distinct and unrelated compounds that do not cross-react.¹

Common Sources of Sulfite Exposure

From a morning glass of juice to an evening shower, in the pharmacy and at the hair salon, sulfite exposure is ubiquitous in most daily routines. Sulfites are present in many foods and beverages, either as a byproduct of natural fermentation or as an additive to prevent spoiling and color change. The Table provides examples of foods with high sulfite content.^1,4-6 In particular, dried fruit, bottled lemon juice, wine, grape juice, sauerkraut juice, and pickled onions have high sulfite content.

Topical medications and personal care products represent other potential sources of sulfite exposure. A number of reports have shown that sulfites may be included in topical steroids,⁷ antibiotics,⁸ antifungals,⁹ hemorrhoidal preparations,¹⁰ local anesthetics,¹¹ and urinary catheterization gel,¹² highlighting their many potential applications. In addition, a comprehensive ingredient analysis of 264 ophthalmic medications found that 3.8% of the products contained sodium disulfite.¹³ Sulfites may be found in personal care products, including facial and hand cleansers, shampoos, moisturizers, and toothpastes. Hair dyes also commonly contain sulfites,⁷ which are listed in as many as 90% of hair dye kits in the ACDS Contact Allergen Management Program database.¹

Occupational exposures also are widespread, as sulfites are extensively utilized across diverse industries such as pharmaceuticals, health care, leather manufacturing, mineral extraction, food preparation, chemical manufacturing, textiles, alcohol brewing, and wine production.¹

Sulfites also are used in the rubber industry—­particularly in gloves—due to their anticoagulant and preservative properties.⁴ This is relevant to health care providers, who may use dozens of disposable gloves in a single day. In an experimental pilot study, ­researchers detected sulfites in 83% (5/6) of natural rubber latex gloves, 96% (23/24) of synthetic (nitrile) gloves, and 0% (0/5) of polyvinyl chloride gloves.¹⁴ While this study was limited to a small sample size, it demonstrates the common use of sulfites in certain rubber gloves and encourages future studies to determine whether there is a quantitative threshold to elicit allergic reactions.

Sulfite Allergy

In 1968, an early case report of ACD to sulfites was published involving a pharmaceutical worker who developed hand eczema after working at a factory for 3 months and had a positive patch test to potassium metabisulfite.¹⁵ There have been other cases published in the literature since then, including localized ACD as well as less common cases of systemic contact dermatitis following oral, injectable, and rectal sulfite exposures.¹⁶

The North American Contact Dermatitis Group found that, among 132 (2.7%) of 4885 patients with positive patch tests to sodium disulfite from 2017 to 2018, the most commonly involved body sites were the face (28.8%) and hands (20.5%) followed by a scattered/generalized distribution (13.6%). Involvement of the face and hands may correlate with the most frequent sources of exposure that were identified, including personal care products (particularly hair dyes)(18.9%), medications (9.1%), and foods (7.6%).¹⁷ A multicenter analysis of patch test results from Germany, Austria, and Switzerland from 1999 to 2013 showed that 357 (2.9%) of 12,156 patients had positive reactions to sodium disulfite, with the most commonly identified exposure sources being topical pharmaceutical agents (59.3%); cosmetics, creams, and sunscreens (13.6%); and systemic drugs (6.8%).¹⁸ However, it is not always possible to determine the clinical relevance of a positive patch test to sulfites.¹

Other than the face and hands, there have been other unexpected anatomic locations for sulfite ACD (eg, the lower back), and systemic contact dermatitis has manifested with widespread rashes due to oral, rectal, and parenteral exposure.^4,16,19 There is no definitive link between sulfite contact allergy and patient sex, but there seems to be a higher prevalence in patients older than 40 years, perhaps related to overall lifetime exposure.¹

Immediate hypersensitivity reactions to sulfites also have been reported, including urticaria, angioedema, and anaphylaxis.⁴ Due to multiple cases of severe dermatologic and respiratory reactions to food products containing sulfites,²⁰ the US Food and Drug Administration prohibited their use in fresh fruit and vegetables as antibrowning agents in 1986 and required labels on packaged foods that contained sulfites at more than 10 parts per million.²¹ However, food and drinks produced in restaurants, bakeries, and cafes as well as those that are distributed directly to consumers from the preparation site are exempt from these rules.¹⁷

In addition, consuming high amounts of dietary sulfites has been linked to headaches through unclear (ie, not necessarily allergic) mechanisms.^4,22 One study found that wine with a higher sulfite concentration was associated with increased risk for headaches in participants who had a history of headaches related to wine consumption.²²

Patch Testing to Sulfites

The North American Contact Dermatitis Group has tested sodium disulfite since 2017 and found an increased frequency of positive patch tests from 2.7% (N=4885) in 2017 and 2018¹⁷ to 3.3% (N=4115) in 2019 and 2020²³ among patients referred for testing. Similarly, patch testing to sodium disulfite in nearly 40,000 patients in 9 European countries showed a pooled prevalence of reactions of 3.1%.¹⁷ However, this contact allergy may go unrecognized, as sulfites are not included in common patch test series, including the thin-layer rapid use epicutaneous test and the ACDS Core Allergen Series.^24,25 The relatively high patch test positivity to sulfites along with the prevalence of daily exposures supports the addition of sulfites to more patch test screening series.

The recommended patch test concentration for sodium disulfite is 1% in petrolatum.⁵ Testing in aqueous solutions is not recommended because they can cause sulfites to break down, potentially producing false-positive or irritant patch test reactions.^7,26,27

Recommendations for Patients With Sulfite Allergies

Individuals with contact allergies to sulfites should be counseled on exposure sources and should be given resources providing a list of safe products, such as the ACDS Contact Allergen Management Program (https://www.acdscamp.org/login) or SkinSAFE ­(https://www.skinsafeproducts.com/). Prescribers should be cognizant of sulfites that are present in prescription medications. Just because a patient has a positive patch test to sulfites does not automatically imply that they will need to modify their diet to avoid sulfite-containing foods; in the absence of cheilitis or a distribution suggestive of systemic contact dermatitis (eg, vesicular hand/foot dermatitis, intertriginous eruptions), this step may be unnecessary. On the other hand, individuals who have experienced immediate hypersensitivity reactions to sulfites should avoid sulfite-containing foods and carry an epinephrine autoinjector.

Final Interpretation

Sulfites are ubiquitous compounds found in various foods, beverages, medications, and personal care products in addition to a range of occupational exposures. The face and hands are the most common sites of sulfite ACD. Despite patch test positivity in as many as 3% of tested patients,^17,23 sulfite allergy may be missed due to lack of routine testing on standard screening series.

The American Contact Dermatitis Society (ACDS) selected sulfites as the 2024 Allergen of the Year.¹ Due to their preservative and antioxidant properties, sulfites are prevalent in a variety of foods, beverages, medications, and personal care products; however, sulfites also have been implicated as a potential contact allergen. In this article, we review common sources of sulfite exposure, clinical manifestations of allergic contact dermatitis (ACD) to sulfites, and patch testing considerations for this emerging allergen.

What Are Sulfites?

Sulfiting agents are compounds that contain the sulfite ion SO₃^2-, including sulfur dioxide, sodium disulfite (sodium metabisulfite), and potassium metabisulfite.² Sulfites occur naturally in the environment and commonly are used as preservatives, antibrowning agents, and antioxidants in various foods, beverages, medications, cosmetics, and skin care products. As antibrowning agents and antioxidants, sulfites help maintain the natural appearance of foods and other products and prevent premature spoiling by inactivating oxidative enzymes.³ It should be noted that sulfites and sulfates are distinct and unrelated compounds that do not cross-react.¹

Common Sources of Sulfite Exposure

From a morning glass of juice to an evening shower, in the pharmacy and at the hair salon, sulfite exposure is ubiquitous in most daily routines. Sulfites are present in many foods and beverages, either as a byproduct of natural fermentation or as an additive to prevent spoiling and color change. The Table provides examples of foods with high sulfite content.^1,4-6 In particular, dried fruit, bottled lemon juice, wine, grape juice, sauerkraut juice, and pickled onions have high sulfite content.

Topical medications and personal care products represent other potential sources of sulfite exposure. A number of reports have shown that sulfites may be included in topical steroids,⁷ antibiotics,⁸ antifungals,⁹ hemorrhoidal preparations,¹⁰ local anesthetics,¹¹ and urinary catheterization gel,¹² highlighting their many potential applications. In addition, a comprehensive ingredient analysis of 264 ophthalmic medications found that 3.8% of the products contained sodium disulfite.¹³ Sulfites may be found in personal care products, including facial and hand cleansers, shampoos, moisturizers, and toothpastes. Hair dyes also commonly contain sulfites,⁷ which are listed in as many as 90% of hair dye kits in the ACDS Contact Allergen Management Program database.¹

Occupational exposures also are widespread, as sulfites are extensively utilized across diverse industries such as pharmaceuticals, health care, leather manufacturing, mineral extraction, food preparation, chemical manufacturing, textiles, alcohol brewing, and wine production.¹

Sulfites also are used in the rubber industry—­particularly in gloves—due to their anticoagulant and preservative properties.⁴ This is relevant to health care providers, who may use dozens of disposable gloves in a single day. In an experimental pilot study, ­researchers detected sulfites in 83% (5/6) of natural rubber latex gloves, 96% (23/24) of synthetic (nitrile) gloves, and 0% (0/5) of polyvinyl chloride gloves.¹⁴ While this study was limited to a small sample size, it demonstrates the common use of sulfites in certain rubber gloves and encourages future studies to determine whether there is a quantitative threshold to elicit allergic reactions.

Sulfite Allergy

In 1968, an early case report of ACD to sulfites was published involving a pharmaceutical worker who developed hand eczema after working at a factory for 3 months and had a positive patch test to potassium metabisulfite.¹⁵ There have been other cases published in the literature since then, including localized ACD as well as less common cases of systemic contact dermatitis following oral, injectable, and rectal sulfite exposures.¹⁶

The North American Contact Dermatitis Group found that, among 132 (2.7%) of 4885 patients with positive patch tests to sodium disulfite from 2017 to 2018, the most commonly involved body sites were the face (28.8%) and hands (20.5%) followed by a scattered/generalized distribution (13.6%). Involvement of the face and hands may correlate with the most frequent sources of exposure that were identified, including personal care products (particularly hair dyes)(18.9%), medications (9.1%), and foods (7.6%).¹⁷ A multicenter analysis of patch test results from Germany, Austria, and Switzerland from 1999 to 2013 showed that 357 (2.9%) of 12,156 patients had positive reactions to sodium disulfite, with the most commonly identified exposure sources being topical pharmaceutical agents (59.3%); cosmetics, creams, and sunscreens (13.6%); and systemic drugs (6.8%).¹⁸ However, it is not always possible to determine the clinical relevance of a positive patch test to sulfites.¹

Other than the face and hands, there have been other unexpected anatomic locations for sulfite ACD (eg, the lower back), and systemic contact dermatitis has manifested with widespread rashes due to oral, rectal, and parenteral exposure.^4,16,19 There is no definitive link between sulfite contact allergy and patient sex, but there seems to be a higher prevalence in patients older than 40 years, perhaps related to overall lifetime exposure.¹

Immediate hypersensitivity reactions to sulfites also have been reported, including urticaria, angioedema, and anaphylaxis.⁴ Due to multiple cases of severe dermatologic and respiratory reactions to food products containing sulfites,²⁰ the US Food and Drug Administration prohibited their use in fresh fruit and vegetables as antibrowning agents in 1986 and required labels on packaged foods that contained sulfites at more than 10 parts per million.²¹ However, food and drinks produced in restaurants, bakeries, and cafes as well as those that are distributed directly to consumers from the preparation site are exempt from these rules.¹⁷

In addition, consuming high amounts of dietary sulfites has been linked to headaches through unclear (ie, not necessarily allergic) mechanisms.^4,22 One study found that wine with a higher sulfite concentration was associated with increased risk for headaches in participants who had a history of headaches related to wine consumption.²²

Patch Testing to Sulfites

The North American Contact Dermatitis Group has tested sodium disulfite since 2017 and found an increased frequency of positive patch tests from 2.7% (N=4885) in 2017 and 2018¹⁷ to 3.3% (N=4115) in 2019 and 2020²³ among patients referred for testing. Similarly, patch testing to sodium disulfite in nearly 40,000 patients in 9 European countries showed a pooled prevalence of reactions of 3.1%.¹⁷ However, this contact allergy may go unrecognized, as sulfites are not included in common patch test series, including the thin-layer rapid use epicutaneous test and the ACDS Core Allergen Series.^24,25 The relatively high patch test positivity to sulfites along with the prevalence of daily exposures supports the addition of sulfites to more patch test screening series.

The recommended patch test concentration for sodium disulfite is 1% in petrolatum.⁵ Testing in aqueous solutions is not recommended because they can cause sulfites to break down, potentially producing false-positive or irritant patch test reactions.^7,26,27

Recommendations for Patients With Sulfite Allergies

Individuals with contact allergies to sulfites should be counseled on exposure sources and should be given resources providing a list of safe products, such as the ACDS Contact Allergen Management Program (https://www.acdscamp.org/login) or SkinSAFE ­(https://www.skinsafeproducts.com/). Prescribers should be cognizant of sulfites that are present in prescription medications. Just because a patient has a positive patch test to sulfites does not automatically imply that they will need to modify their diet to avoid sulfite-containing foods; in the absence of cheilitis or a distribution suggestive of systemic contact dermatitis (eg, vesicular hand/foot dermatitis, intertriginous eruptions), this step may be unnecessary. On the other hand, individuals who have experienced immediate hypersensitivity reactions to sulfites should avoid sulfite-containing foods and carry an epinephrine autoinjector.

Final Interpretation

Sulfites are ubiquitous compounds found in various foods, beverages, medications, and personal care products in addition to a range of occupational exposures. The face and hands are the most common sites of sulfite ACD. Despite patch test positivity in as many as 3% of tested patients,^17,23 sulfite allergy may be missed due to lack of routine testing on standard screening series.

The American Contact Dermatitis Society (ACDS) selected sulfites as the 2024 Allergen of the Year.¹ Due to their preservative and antioxidant properties, sulfites are prevalent in a variety of foods, beverages, medications, and personal care products; however, sulfites also have been implicated as a potential contact allergen. In this article, we review common sources of sulfite exposure, clinical manifestations of allergic contact dermatitis (ACD) to sulfites, and patch testing considerations for this emerging allergen.

What Are Sulfites?

Sulfiting agents are compounds that contain the sulfite ion SO₃^2-, including sulfur dioxide, sodium disulfite (sodium metabisulfite), and potassium metabisulfite.² Sulfites occur naturally in the environment and commonly are used as preservatives, antibrowning agents, and antioxidants in various foods, beverages, medications, cosmetics, and skin care products. As antibrowning agents and antioxidants, sulfites help maintain the natural appearance of foods and other products and prevent premature spoiling by inactivating oxidative enzymes.³ It should be noted that sulfites and sulfates are distinct and unrelated compounds that do not cross-react.¹

Common Sources of Sulfite Exposure

From a morning glass of juice to an evening shower, in the pharmacy and at the hair salon, sulfite exposure is ubiquitous in most daily routines. Sulfites are present in many foods and beverages, either as a byproduct of natural fermentation or as an additive to prevent spoiling and color change. The Table provides examples of foods with high sulfite content.^1,4-6 In particular, dried fruit, bottled lemon juice, wine, grape juice, sauerkraut juice, and pickled onions have high sulfite content.

Topical medications and personal care products represent other potential sources of sulfite exposure. A number of reports have shown that sulfites may be included in topical steroids,⁷ antibiotics,⁸ antifungals,⁹ hemorrhoidal preparations,¹⁰ local anesthetics,¹¹ and urinary catheterization gel,¹² highlighting their many potential applications. In addition, a comprehensive ingredient analysis of 264 ophthalmic medications found that 3.8% of the products contained sodium disulfite.¹³ Sulfites may be found in personal care products, including facial and hand cleansers, shampoos, moisturizers, and toothpastes. Hair dyes also commonly contain sulfites,⁷ which are listed in as many as 90% of hair dye kits in the ACDS Contact Allergen Management Program database.¹

Occupational exposures also are widespread, as sulfites are extensively utilized across diverse industries such as pharmaceuticals, health care, leather manufacturing, mineral extraction, food preparation, chemical manufacturing, textiles, alcohol brewing, and wine production.¹

Sulfites also are used in the rubber industry—­particularly in gloves—due to their anticoagulant and preservative properties.⁴ This is relevant to health care providers, who may use dozens of disposable gloves in a single day. In an experimental pilot study, ­researchers detected sulfites in 83% (5/6) of natural rubber latex gloves, 96% (23/24) of synthetic (nitrile) gloves, and 0% (0/5) of polyvinyl chloride gloves.¹⁴ While this study was limited to a small sample size, it demonstrates the common use of sulfites in certain rubber gloves and encourages future studies to determine whether there is a quantitative threshold to elicit allergic reactions.

Sulfite Allergy

In 1968, an early case report of ACD to sulfites was published involving a pharmaceutical worker who developed hand eczema after working at a factory for 3 months and had a positive patch test to potassium metabisulfite.¹⁵ There have been other cases published in the literature since then, including localized ACD as well as less common cases of systemic contact dermatitis following oral, injectable, and rectal sulfite exposures.¹⁶

The North American Contact Dermatitis Group found that, among 132 (2.7%) of 4885 patients with positive patch tests to sodium disulfite from 2017 to 2018, the most commonly involved body sites were the face (28.8%) and hands (20.5%) followed by a scattered/generalized distribution (13.6%). Involvement of the face and hands may correlate with the most frequent sources of exposure that were identified, including personal care products (particularly hair dyes)(18.9%), medications (9.1%), and foods (7.6%).¹⁷ A multicenter analysis of patch test results from Germany, Austria, and Switzerland from 1999 to 2013 showed that 357 (2.9%) of 12,156 patients had positive reactions to sodium disulfite, with the most commonly identified exposure sources being topical pharmaceutical agents (59.3%); cosmetics, creams, and sunscreens (13.6%); and systemic drugs (6.8%).¹⁸ However, it is not always possible to determine the clinical relevance of a positive patch test to sulfites.¹

Other than the face and hands, there have been other unexpected anatomic locations for sulfite ACD (eg, the lower back), and systemic contact dermatitis has manifested with widespread rashes due to oral, rectal, and parenteral exposure.^4,16,19 There is no definitive link between sulfite contact allergy and patient sex, but there seems to be a higher prevalence in patients older than 40 years, perhaps related to overall lifetime exposure.¹

Immediate hypersensitivity reactions to sulfites also have been reported, including urticaria, angioedema, and anaphylaxis.⁴ Due to multiple cases of severe dermatologic and respiratory reactions to food products containing sulfites,²⁰ the US Food and Drug Administration prohibited their use in fresh fruit and vegetables as antibrowning agents in 1986 and required labels on packaged foods that contained sulfites at more than 10 parts per million.²¹ However, food and drinks produced in restaurants, bakeries, and cafes as well as those that are distributed directly to consumers from the preparation site are exempt from these rules.¹⁷

In addition, consuming high amounts of dietary sulfites has been linked to headaches through unclear (ie, not necessarily allergic) mechanisms.^4,22 One study found that wine with a higher sulfite concentration was associated with increased risk for headaches in participants who had a history of headaches related to wine consumption.²²

Patch Testing to Sulfites

The North American Contact Dermatitis Group has tested sodium disulfite since 2017 and found an increased frequency of positive patch tests from 2.7% (N=4885) in 2017 and 2018¹⁷ to 3.3% (N=4115) in 2019 and 2020²³ among patients referred for testing. Similarly, patch testing to sodium disulfite in nearly 40,000 patients in 9 European countries showed a pooled prevalence of reactions of 3.1%.¹⁷ However, this contact allergy may go unrecognized, as sulfites are not included in common patch test series, including the thin-layer rapid use epicutaneous test and the ACDS Core Allergen Series.^24,25 The relatively high patch test positivity to sulfites along with the prevalence of daily exposures supports the addition of sulfites to more patch test screening series.

The recommended patch test concentration for sodium disulfite is 1% in petrolatum.⁵ Testing in aqueous solutions is not recommended because they can cause sulfites to break down, potentially producing false-positive or irritant patch test reactions.^7,26,27

Recommendations for Patients With Sulfite Allergies

Individuals with contact allergies to sulfites should be counseled on exposure sources and should be given resources providing a list of safe products, such as the ACDS Contact Allergen Management Program (https://www.acdscamp.org/login) or SkinSAFE ­(https://www.skinsafeproducts.com/). Prescribers should be cognizant of sulfites that are present in prescription medications. Just because a patient has a positive patch test to sulfites does not automatically imply that they will need to modify their diet to avoid sulfite-containing foods; in the absence of cheilitis or a distribution suggestive of systemic contact dermatitis (eg, vesicular hand/foot dermatitis, intertriginous eruptions), this step may be unnecessary. On the other hand, individuals who have experienced immediate hypersensitivity reactions to sulfites should avoid sulfite-containing foods and carry an epinephrine autoinjector.

Final Interpretation

Sulfites are ubiquitous compounds found in various foods, beverages, medications, and personal care products in addition to a range of occupational exposures. The face and hands are the most common sites of sulfite ACD. Despite patch test positivity in as many as 3% of tested patients,^17,23 sulfite allergy may be missed due to lack of routine testing on standard screening series.

THE DIAGNOSIS: Habit-Tic Deformity

Habit-tic deformity is a cause of nail dystrophy that commonly arises in children and adults due to subconscious repetitive and self-injurious manipulation of the nail bed or cuticle, which ultimately damages the nail matrix.^1,2 It can be considered a variant of onychotillomania.¹

Characteristic features of habit-tic deformity include a longitudinal depression on the central nail plate with transverse ridges,¹ which can be more prominent on the dominant hand.³ Patients typically note a long duration of nail deformity, often without insight into its etiology.² Diagnosis relies on careful assessment of the clinical presentation and the patient’s history to rule out other differential diagnoses. Based on our patient’s clinical presentation and history, we excluded wart, squamous cell carcinoma, eczema, psoriasis, lichen planus, autoimmune connective tissue disease, onychomycosis, paronychia, pincer nail deformity, and Beau line as potential diagnoses. Biopsy also can be performed to exclude these diagnoses from the differential if the cause is unclear following clinical examination.

Treatment for habit-tic deformity involves identifying and addressing the underlying habit. Barrier methods such as bandages and cyanoacrylate adhesives that prevent further manipulation of the nail matrix are effective treatments for habit-tic deformity.² A multidisciplinary approach with psychiatry may be optimal to identify underlying psychological comorbidities and break the habit through behavior interventions and medications.⁴ Nail dystrophy generally improves once the habit is disrupted; however, a younger age of onset may carry a worse prognosis.³ Patients should be counseled that the affected nail may never grow normally.

Our patient was advised to use fluocinonide ointment 0.05% to reduce inflammation of the proximal nail fold and to cover the thumbnail with a bandage to prevent picking. He also was counseled that the nail may show ongoing abnormal growth. Minimal improvement was noted after 6 months.

THE DIAGNOSIS: Habit-Tic Deformity

Habit-tic deformity is a cause of nail dystrophy that commonly arises in children and adults due to subconscious repetitive and self-injurious manipulation of the nail bed or cuticle, which ultimately damages the nail matrix.^1,2 It can be considered a variant of onychotillomania.¹

Characteristic features of habit-tic deformity include a longitudinal depression on the central nail plate with transverse ridges,¹ which can be more prominent on the dominant hand.³ Patients typically note a long duration of nail deformity, often without insight into its etiology.² Diagnosis relies on careful assessment of the clinical presentation and the patient’s history to rule out other differential diagnoses. Based on our patient’s clinical presentation and history, we excluded wart, squamous cell carcinoma, eczema, psoriasis, lichen planus, autoimmune connective tissue disease, onychomycosis, paronychia, pincer nail deformity, and Beau line as potential diagnoses. Biopsy also can be performed to exclude these diagnoses from the differential if the cause is unclear following clinical examination.

Treatment for habit-tic deformity involves identifying and addressing the underlying habit. Barrier methods such as bandages and cyanoacrylate adhesives that prevent further manipulation of the nail matrix are effective treatments for habit-tic deformity.² A multidisciplinary approach with psychiatry may be optimal to identify underlying psychological comorbidities and break the habit through behavior interventions and medications.⁴ Nail dystrophy generally improves once the habit is disrupted; however, a younger age of onset may carry a worse prognosis.³ Patients should be counseled that the affected nail may never grow normally.

Our patient was advised to use fluocinonide ointment 0.05% to reduce inflammation of the proximal nail fold and to cover the thumbnail with a bandage to prevent picking. He also was counseled that the nail may show ongoing abnormal growth. Minimal improvement was noted after 6 months.

THE DIAGNOSIS: Habit-Tic Deformity

Habit-tic deformity is a cause of nail dystrophy that commonly arises in children and adults due to subconscious repetitive and self-injurious manipulation of the nail bed or cuticle, which ultimately damages the nail matrix.^1,2 It can be considered a variant of onychotillomania.¹

Characteristic features of habit-tic deformity include a longitudinal depression on the central nail plate with transverse ridges,¹ which can be more prominent on the dominant hand.³ Patients typically note a long duration of nail deformity, often without insight into its etiology.² Diagnosis relies on careful assessment of the clinical presentation and the patient’s history to rule out other differential diagnoses. Based on our patient’s clinical presentation and history, we excluded wart, squamous cell carcinoma, eczema, psoriasis, lichen planus, autoimmune connective tissue disease, onychomycosis, paronychia, pincer nail deformity, and Beau line as potential diagnoses. Biopsy also can be performed to exclude these diagnoses from the differential if the cause is unclear following clinical examination.

Treatment for habit-tic deformity involves identifying and addressing the underlying habit. Barrier methods such as bandages and cyanoacrylate adhesives that prevent further manipulation of the nail matrix are effective treatments for habit-tic deformity.² A multidisciplinary approach with psychiatry may be optimal to identify underlying psychological comorbidities and break the habit through behavior interventions and medications.⁴ Nail dystrophy generally improves once the habit is disrupted; however, a younger age of onset may carry a worse prognosis.³ Patients should be counseled that the affected nail may never grow normally.

Our patient was advised to use fluocinonide ointment 0.05% to reduce inflammation of the proximal nail fold and to cover the thumbnail with a bandage to prevent picking. He also was counseled that the nail may show ongoing abnormal growth. Minimal improvement was noted after 6 months.

The latest data on myasthenia gravis (MG) research, reported at the American Association of Neuromuscular and Electrodiagnostic Medicine 2024 Annual Meeting, are presented by Dr Pushpa Narayanswami of Harvard Medical School in Boston, Massachusetts.  

Dr Narayanswami begins with a safety, tolerability, and efficacy study for subcutaneous efgartigimod. Results showed that the mean change in MG activities of daily living (MG-ADL) was no different between the fixed-dose and cyclic regimens, demonstrating another dosage option for patients.

Next, Dr Narayanswami discusses two separate complement C5 inhibitor therapy trials. The first was a global registry study looking at ravulizumab. Patient cohorts consisted of those who started and remained on ravulizumab vs another that switched from initial eculizumab to ravulizumab. In both groups, MG-ADL was improved. The other study investigated zilucoplan in acetylcholine receptor autoantibody–positive generalized MG patient populations; similarly, researchers found favorable results.

She then details a study looking at the safety outcomes in pregnant patients treated with eculizumab. Because of limited disease-specific data in the registry, further investigation is recommended.

Finally, Dr Narayanaswami examines results for inebilizumab, a first-in-class anti-CD19 B cell–depleting agent. The drug demonstrated safety and beneficial efficacy compared with placebo in seropositive generalized MG patients.

--

Pushpa Narayanaswami, MD, Associate Professor, Department of Neurology, Harvard Medical School; Vice Chair of Clinical Operations, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Pushpa Narayanaswami, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Alexion; Argenx; Janssen; Dianthus; UCB; GSK

Received research grant from: Alexion; UCB; Dianthus; Janssen

The latest data on myasthenia gravis (MG) research, reported at the American Association of Neuromuscular and Electrodiagnostic Medicine 2024 Annual Meeting, are presented by Dr Pushpa Narayanswami of Harvard Medical School in Boston, Massachusetts.  

Dr Narayanswami begins with a safety, tolerability, and efficacy study for subcutaneous efgartigimod. Results showed that the mean change in MG activities of daily living (MG-ADL) was no different between the fixed-dose and cyclic regimens, demonstrating another dosage option for patients.

Next, Dr Narayanswami discusses two separate complement C5 inhibitor therapy trials. The first was a global registry study looking at ravulizumab. Patient cohorts consisted of those who started and remained on ravulizumab vs another that switched from initial eculizumab to ravulizumab. In both groups, MG-ADL was improved. The other study investigated zilucoplan in acetylcholine receptor autoantibody–positive generalized MG patient populations; similarly, researchers found favorable results.

She then details a study looking at the safety outcomes in pregnant patients treated with eculizumab. Because of limited disease-specific data in the registry, further investigation is recommended.

Finally, Dr Narayanaswami examines results for inebilizumab, a first-in-class anti-CD19 B cell–depleting agent. The drug demonstrated safety and beneficial efficacy compared with placebo in seropositive generalized MG patients.

--

Pushpa Narayanaswami, MD, Associate Professor, Department of Neurology, Harvard Medical School; Vice Chair of Clinical Operations, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Pushpa Narayanaswami, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Alexion; Argenx; Janssen; Dianthus; UCB; GSK

Received research grant from: Alexion; UCB; Dianthus; Janssen

The latest data on myasthenia gravis (MG) research, reported at the American Association of Neuromuscular and Electrodiagnostic Medicine 2024 Annual Meeting, are presented by Dr Pushpa Narayanswami of Harvard Medical School in Boston, Massachusetts.  

Dr Narayanswami begins with a safety, tolerability, and efficacy study for subcutaneous efgartigimod. Results showed that the mean change in MG activities of daily living (MG-ADL) was no different between the fixed-dose and cyclic regimens, demonstrating another dosage option for patients.

Next, Dr Narayanswami discusses two separate complement C5 inhibitor therapy trials. The first was a global registry study looking at ravulizumab. Patient cohorts consisted of those who started and remained on ravulizumab vs another that switched from initial eculizumab to ravulizumab. In both groups, MG-ADL was improved. The other study investigated zilucoplan in acetylcholine receptor autoantibody–positive generalized MG patient populations; similarly, researchers found favorable results.

She then details a study looking at the safety outcomes in pregnant patients treated with eculizumab. Because of limited disease-specific data in the registry, further investigation is recommended.

Finally, Dr Narayanaswami examines results for inebilizumab, a first-in-class anti-CD19 B cell–depleting agent. The drug demonstrated safety and beneficial efficacy compared with placebo in seropositive generalized MG patients.

--

Pushpa Narayanaswami, MD, Associate Professor, Department of Neurology, Harvard Medical School; Vice Chair of Clinical Operations, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Pushpa Narayanaswami, MD, has disclosed the following relevant financial relationships:

Serve(d) as an advisor or consultant for: Alexion; Argenx; Janssen; Dianthus; UCB; GSK

Received research grant from: Alexion; UCB; Dianthus; Janssen

More than 37 million Americans have diabetes mellitus (DM), and approximately 90% have type 2 DM (T2DM), including about 25% of veterans.^1,2 The current guidelines suggest that therapy depends on a patient's comorbidities, management needs, and patient-centered treatment factors.³ About 1 in 3 adults with DM have chronic kidney disease (CKD), defined as the presence of kidney damage or an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m², persisting for ≥ 3 months.⁴

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of antihyperglycemic agents acting on the SGLT-2 proteins expressed in the renal proximal convoluted tubules. They exert their effects by preventing the reabsorption of filtered glucose from the tubular lumen. There are 4 SGLT-2 inhibitors approved by the US Food and Drug Administration: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Empagliflozin is currently the preferred SGLT-2 inhibitor on the US Department of Veterans Affairs (VA) formulary.

According to the American Diabetes Association guidelines, empagliflozin is considered when an individual has or is at risk for atherosclerotic cardiovascular disease, heart failure, and CKD.³ SGLT-2 inhibitors are a favorable option due to their low risk for hypoglycemia while also promoting weight loss. The EMPEROR-Reduced trial demonstrated that, in addition to benefits for patients with heart failure, empagliflozin also slowed the progressive decline in kidney function in those with and without DM.⁵ The purpose of this study was to evaluate the effectiveness of empagliflozin on hemoglobin A_1c (HbA_1c) levels in patients with CKD at the Hershel “Woody” Williams VA Medical Center (HWWVAMC) in Huntington, West Virginia, along with other laboratory test markers.

Methods

The Marshall University Institutional Review Board #1 (Medical) and the HWWVAMC institutional review board and research and development committee each reviewed and approved this study. A retrospective chart review was conducted on patients diagnosed with T2DM and stage 3 CKD who were prescribed empagliflozin for DM management between January 1, 2015, and October 1, 2022, yielding 1771 patients. Data were obtained through the VHA Corporate Data Warehouse (CDW) and stored on the VA Informatics and Computing Infrastructure (VINCI) research server.

Patients were included if they were aged 18 to 89 years, prescribed empagliflozin by a VA clinician for the treatment of T2DM, had an eGFR between 30 and 59 mL/min/1.73 m², and had an initial HbA_1c between 7% and 10%. Using further random sampling, patients were either excluded or divided into, those with stage 3a CKD and those with stage 3b CKD. The primary endpoint of this study was the change in HbA_1c levels in patients with stage 3b CKD (eGFR 30-44 mL/min/1.73 m²) compared with stage 3a (eGFR 45-59 mL/min/1.73 m²) after 12 months. The secondary endpoints included effects on renal function, weight, blood pressure, incidence of adverse drug events, and cardiovascular events. Of the excluded, 38 had HbA_1c < 7%, 30 had HbA_1c ≥ 10%, 21 did not have data at 1-year mark, 15 had the medication discontinued due to decline in renal function, 14 discontinued their medication without documented reason, 10 discontinued their medication due to adverse drug reactions (ADRs), 12 had eGFR > 60 mL/ min/1.73 m², 9 died within 1 year of initiation, 4 had eGFR < 30 mL/min/1.73 m², 1 had no baseline eGFR, and 1 was the spouse of a veteran.

Statistical Analysis

All statistical analyses were performed using STATA v.15. We used t tests to examine changes within each group, along with paired t tests to compare the 2 groups. Two-sample t tests were used to analyze the continuous data at both the primary and secondary endpoints.

Results

Of the 1771 patients included in the initial data set, a randomized sample of 255 charts were reviewed, 155 were excluded, and 100 were included. Fifty patients, had stage 3a CKD and 50 had stage 3b CKD. Baseline demographics were similar between the stage 3a and 3b groups (Table 1). Both groups were predominantly White and male, with mean age > 70 years.

The primary endpoint was the differences in HbA_1c levels over time and between groups for patients with stage 3a and stage 3b CKD 1 year after initiation of empagliflozin. The starting doses of empagliflozin were either 12.5 mg or 25.0 mg. For both groups, the changes in HbA_1c levels were statistically significant (Table 2). HbA_1c levels dropped 0.65% for the stage 3a group and 0.48% for the 3b group. When compared to one another, the results were not statistically significant (P = .51).

Secondary Endpoint

There was no statistically significant difference in serum creatinine levels within each group between baselines and 1 year later for the stage 3a (P = .21) and stage 3b (P = .22) groups, or when compared to each other (P = .67). There were statistically significant changes in weight for patients in the stage 3a group (P < .05), but not for stage 3b group (P = .06) or when compared to each other (P = .41). A statistically significant change in systolic blood pressure was observed for the stage 3a group (P = .003), but not the stage 3b group (P = .16) or when compared to each other (P = .27). There were statistically significant changes in diastolic blood pressure within the stage 3a group (P = .04), but not within the stage 3b group (P = .61) or when compared to each other (P = .31).

Ten patients discontinued empagliflozin before the 1-year mark due to ADRs, including dizziness, increased incidence of urinary tract infections, rash, and tachycardia (Table 3). Additionally, 3 ADRs resulted in the empagliflozin discontinuation after 1 year (Table 3).

Discussion

This study showed a statistically significant change in HbA_1c levels for patients with stage 3a and stage 3b CKD. With eGFR levels in these 2 groups > 30 mL/min/1.73 m², patients were able to achieve glycemic benefits. There were no significant changes to the serum creatinine levels. Both groups saw statistically significant changes in weight loss within their own group; however, there were no statistically significant changes when compared to each other. With both systolic and diastolic blood pressure, the stage 3a group had statistically significant changes.

The EMPA-REG BP study demonstrated that empagliflozin was associated with significant and clinically meaningful reductions in blood pressure and HbA_1c levels compared with placebo and was well tolerated in patients with T2DM and hypertension.^6,7,8

Limitations

This study had a retrospective study design, which resulted in missing information for many patients and higher rates of exclusion. The population was predominantly older, White, and male and may not reflect other populations. The starting doses of empagliflozin varied between the groups. The VA employs tablet splitting for some patients, and the available doses were either 10.0 mg, 12.5 mg, or 25.0 mg. Some prescribers start veterans at lower doses and gradually increase to the higher dose of 25.0 mg, adding to the variability in starting doses.

Patients with eGFR < 30 mL/min/1.73 m² make it difficult to determine any potential benefit in this population. The EMPA-KIDNEY trial demonstrated that the benefits of empagliflozin treatment were consistent among patients with or without DM and regardless of eGFR at randomization.⁹ Furthermore, many veterans had an initial HbA_1c levels outside the inclusion criteria range, which was a factor in the smaller sample size.

Conclusions

While the reduction in HbA_1c levels was less in patients with stage 3b CKD compared to patients stage 3a CKD, all patients experienced a benefit. The overall incidence of ADRs was low in the study population, showing empagliflozin as a favorable choice for those with T2DM and CKD. Based on the findings of this study, empagliflozin is a potentially beneficial option for reducing HbA_1c levels in patients with CKD.

More than 37 million Americans have diabetes mellitus (DM), and approximately 90% have type 2 DM (T2DM), including about 25% of veterans.^1,2 The current guidelines suggest that therapy depends on a patient's comorbidities, management needs, and patient-centered treatment factors.³ About 1 in 3 adults with DM have chronic kidney disease (CKD), defined as the presence of kidney damage or an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m², persisting for ≥ 3 months.⁴

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of antihyperglycemic agents acting on the SGLT-2 proteins expressed in the renal proximal convoluted tubules. They exert their effects by preventing the reabsorption of filtered glucose from the tubular lumen. There are 4 SGLT-2 inhibitors approved by the US Food and Drug Administration: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Empagliflozin is currently the preferred SGLT-2 inhibitor on the US Department of Veterans Affairs (VA) formulary.

According to the American Diabetes Association guidelines, empagliflozin is considered when an individual has or is at risk for atherosclerotic cardiovascular disease, heart failure, and CKD.³ SGLT-2 inhibitors are a favorable option due to their low risk for hypoglycemia while also promoting weight loss. The EMPEROR-Reduced trial demonstrated that, in addition to benefits for patients with heart failure, empagliflozin also slowed the progressive decline in kidney function in those with and without DM.⁵ The purpose of this study was to evaluate the effectiveness of empagliflozin on hemoglobin A_1c (HbA_1c) levels in patients with CKD at the Hershel “Woody” Williams VA Medical Center (HWWVAMC) in Huntington, West Virginia, along with other laboratory test markers.

Methods

The Marshall University Institutional Review Board #1 (Medical) and the HWWVAMC institutional review board and research and development committee each reviewed and approved this study. A retrospective chart review was conducted on patients diagnosed with T2DM and stage 3 CKD who were prescribed empagliflozin for DM management between January 1, 2015, and October 1, 2022, yielding 1771 patients. Data were obtained through the VHA Corporate Data Warehouse (CDW) and stored on the VA Informatics and Computing Infrastructure (VINCI) research server.

Patients were included if they were aged 18 to 89 years, prescribed empagliflozin by a VA clinician for the treatment of T2DM, had an eGFR between 30 and 59 mL/min/1.73 m², and had an initial HbA_1c between 7% and 10%. Using further random sampling, patients were either excluded or divided into, those with stage 3a CKD and those with stage 3b CKD. The primary endpoint of this study was the change in HbA_1c levels in patients with stage 3b CKD (eGFR 30-44 mL/min/1.73 m²) compared with stage 3a (eGFR 45-59 mL/min/1.73 m²) after 12 months. The secondary endpoints included effects on renal function, weight, blood pressure, incidence of adverse drug events, and cardiovascular events. Of the excluded, 38 had HbA_1c < 7%, 30 had HbA_1c ≥ 10%, 21 did not have data at 1-year mark, 15 had the medication discontinued due to decline in renal function, 14 discontinued their medication without documented reason, 10 discontinued their medication due to adverse drug reactions (ADRs), 12 had eGFR > 60 mL/ min/1.73 m², 9 died within 1 year of initiation, 4 had eGFR < 30 mL/min/1.73 m², 1 had no baseline eGFR, and 1 was the spouse of a veteran.

Statistical Analysis

All statistical analyses were performed using STATA v.15. We used t tests to examine changes within each group, along with paired t tests to compare the 2 groups. Two-sample t tests were used to analyze the continuous data at both the primary and secondary endpoints.

Results

Of the 1771 patients included in the initial data set, a randomized sample of 255 charts were reviewed, 155 were excluded, and 100 were included. Fifty patients, had stage 3a CKD and 50 had stage 3b CKD. Baseline demographics were similar between the stage 3a and 3b groups (Table 1). Both groups were predominantly White and male, with mean age > 70 years.

The primary endpoint was the differences in HbA_1c levels over time and between groups for patients with stage 3a and stage 3b CKD 1 year after initiation of empagliflozin. The starting doses of empagliflozin were either 12.5 mg or 25.0 mg. For both groups, the changes in HbA_1c levels were statistically significant (Table 2). HbA_1c levels dropped 0.65% for the stage 3a group and 0.48% for the 3b group. When compared to one another, the results were not statistically significant (P = .51).

Secondary Endpoint

There was no statistically significant difference in serum creatinine levels within each group between baselines and 1 year later for the stage 3a (P = .21) and stage 3b (P = .22) groups, or when compared to each other (P = .67). There were statistically significant changes in weight for patients in the stage 3a group (P < .05), but not for stage 3b group (P = .06) or when compared to each other (P = .41). A statistically significant change in systolic blood pressure was observed for the stage 3a group (P = .003), but not the stage 3b group (P = .16) or when compared to each other (P = .27). There were statistically significant changes in diastolic blood pressure within the stage 3a group (P = .04), but not within the stage 3b group (P = .61) or when compared to each other (P = .31).

Ten patients discontinued empagliflozin before the 1-year mark due to ADRs, including dizziness, increased incidence of urinary tract infections, rash, and tachycardia (Table 3). Additionally, 3 ADRs resulted in the empagliflozin discontinuation after 1 year (Table 3).

Discussion

This study showed a statistically significant change in HbA_1c levels for patients with stage 3a and stage 3b CKD. With eGFR levels in these 2 groups > 30 mL/min/1.73 m², patients were able to achieve glycemic benefits. There were no significant changes to the serum creatinine levels. Both groups saw statistically significant changes in weight loss within their own group; however, there were no statistically significant changes when compared to each other. With both systolic and diastolic blood pressure, the stage 3a group had statistically significant changes.

The EMPA-REG BP study demonstrated that empagliflozin was associated with significant and clinically meaningful reductions in blood pressure and HbA_1c levels compared with placebo and was well tolerated in patients with T2DM and hypertension.^6,7,8

Limitations

This study had a retrospective study design, which resulted in missing information for many patients and higher rates of exclusion. The population was predominantly older, White, and male and may not reflect other populations. The starting doses of empagliflozin varied between the groups. The VA employs tablet splitting for some patients, and the available doses were either 10.0 mg, 12.5 mg, or 25.0 mg. Some prescribers start veterans at lower doses and gradually increase to the higher dose of 25.0 mg, adding to the variability in starting doses.

Patients with eGFR < 30 mL/min/1.73 m² make it difficult to determine any potential benefit in this population. The EMPA-KIDNEY trial demonstrated that the benefits of empagliflozin treatment were consistent among patients with or without DM and regardless of eGFR at randomization.⁹ Furthermore, many veterans had an initial HbA_1c levels outside the inclusion criteria range, which was a factor in the smaller sample size.

Conclusions

While the reduction in HbA_1c levels was less in patients with stage 3b CKD compared to patients stage 3a CKD, all patients experienced a benefit. The overall incidence of ADRs was low in the study population, showing empagliflozin as a favorable choice for those with T2DM and CKD. Based on the findings of this study, empagliflozin is a potentially beneficial option for reducing HbA_1c levels in patients with CKD.

More than 37 million Americans have diabetes mellitus (DM), and approximately 90% have type 2 DM (T2DM), including about 25% of veterans.^1,2 The current guidelines suggest that therapy depends on a patient's comorbidities, management needs, and patient-centered treatment factors.³ About 1 in 3 adults with DM have chronic kidney disease (CKD), defined as the presence of kidney damage or an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m², persisting for ≥ 3 months.⁴

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of antihyperglycemic agents acting on the SGLT-2 proteins expressed in the renal proximal convoluted tubules. They exert their effects by preventing the reabsorption of filtered glucose from the tubular lumen. There are 4 SGLT-2 inhibitors approved by the US Food and Drug Administration: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Empagliflozin is currently the preferred SGLT-2 inhibitor on the US Department of Veterans Affairs (VA) formulary.

According to the American Diabetes Association guidelines, empagliflozin is considered when an individual has or is at risk for atherosclerotic cardiovascular disease, heart failure, and CKD.³ SGLT-2 inhibitors are a favorable option due to their low risk for hypoglycemia while also promoting weight loss. The EMPEROR-Reduced trial demonstrated that, in addition to benefits for patients with heart failure, empagliflozin also slowed the progressive decline in kidney function in those with and without DM.⁵ The purpose of this study was to evaluate the effectiveness of empagliflozin on hemoglobin A_1c (HbA_1c) levels in patients with CKD at the Hershel “Woody” Williams VA Medical Center (HWWVAMC) in Huntington, West Virginia, along with other laboratory test markers.

Methods

The Marshall University Institutional Review Board #1 (Medical) and the HWWVAMC institutional review board and research and development committee each reviewed and approved this study. A retrospective chart review was conducted on patients diagnosed with T2DM and stage 3 CKD who were prescribed empagliflozin for DM management between January 1, 2015, and October 1, 2022, yielding 1771 patients. Data were obtained through the VHA Corporate Data Warehouse (CDW) and stored on the VA Informatics and Computing Infrastructure (VINCI) research server.

Patients were included if they were aged 18 to 89 years, prescribed empagliflozin by a VA clinician for the treatment of T2DM, had an eGFR between 30 and 59 mL/min/1.73 m², and had an initial HbA_1c between 7% and 10%. Using further random sampling, patients were either excluded or divided into, those with stage 3a CKD and those with stage 3b CKD. The primary endpoint of this study was the change in HbA_1c levels in patients with stage 3b CKD (eGFR 30-44 mL/min/1.73 m²) compared with stage 3a (eGFR 45-59 mL/min/1.73 m²) after 12 months. The secondary endpoints included effects on renal function, weight, blood pressure, incidence of adverse drug events, and cardiovascular events. Of the excluded, 38 had HbA_1c < 7%, 30 had HbA_1c ≥ 10%, 21 did not have data at 1-year mark, 15 had the medication discontinued due to decline in renal function, 14 discontinued their medication without documented reason, 10 discontinued their medication due to adverse drug reactions (ADRs), 12 had eGFR > 60 mL/ min/1.73 m², 9 died within 1 year of initiation, 4 had eGFR < 30 mL/min/1.73 m², 1 had no baseline eGFR, and 1 was the spouse of a veteran.

Statistical Analysis

All statistical analyses were performed using STATA v.15. We used t tests to examine changes within each group, along with paired t tests to compare the 2 groups. Two-sample t tests were used to analyze the continuous data at both the primary and secondary endpoints.

Results

Of the 1771 patients included in the initial data set, a randomized sample of 255 charts were reviewed, 155 were excluded, and 100 were included. Fifty patients, had stage 3a CKD and 50 had stage 3b CKD. Baseline demographics were similar between the stage 3a and 3b groups (Table 1). Both groups were predominantly White and male, with mean age > 70 years.

The primary endpoint was the differences in HbA_1c levels over time and between groups for patients with stage 3a and stage 3b CKD 1 year after initiation of empagliflozin. The starting doses of empagliflozin were either 12.5 mg or 25.0 mg. For both groups, the changes in HbA_1c levels were statistically significant (Table 2). HbA_1c levels dropped 0.65% for the stage 3a group and 0.48% for the 3b group. When compared to one another, the results were not statistically significant (P = .51).

Secondary Endpoint

There was no statistically significant difference in serum creatinine levels within each group between baselines and 1 year later for the stage 3a (P = .21) and stage 3b (P = .22) groups, or when compared to each other (P = .67). There were statistically significant changes in weight for patients in the stage 3a group (P < .05), but not for stage 3b group (P = .06) or when compared to each other (P = .41). A statistically significant change in systolic blood pressure was observed for the stage 3a group (P = .003), but not the stage 3b group (P = .16) or when compared to each other (P = .27). There were statistically significant changes in diastolic blood pressure within the stage 3a group (P = .04), but not within the stage 3b group (P = .61) or when compared to each other (P = .31).

Ten patients discontinued empagliflozin before the 1-year mark due to ADRs, including dizziness, increased incidence of urinary tract infections, rash, and tachycardia (Table 3). Additionally, 3 ADRs resulted in the empagliflozin discontinuation after 1 year (Table 3).

Discussion

This study showed a statistically significant change in HbA_1c levels for patients with stage 3a and stage 3b CKD. With eGFR levels in these 2 groups > 30 mL/min/1.73 m², patients were able to achieve glycemic benefits. There were no significant changes to the serum creatinine levels. Both groups saw statistically significant changes in weight loss within their own group; however, there were no statistically significant changes when compared to each other. With both systolic and diastolic blood pressure, the stage 3a group had statistically significant changes.

The EMPA-REG BP study demonstrated that empagliflozin was associated with significant and clinically meaningful reductions in blood pressure and HbA_1c levels compared with placebo and was well tolerated in patients with T2DM and hypertension.^6,7,8

Limitations

This study had a retrospective study design, which resulted in missing information for many patients and higher rates of exclusion. The population was predominantly older, White, and male and may not reflect other populations. The starting doses of empagliflozin varied between the groups. The VA employs tablet splitting for some patients, and the available doses were either 10.0 mg, 12.5 mg, or 25.0 mg. Some prescribers start veterans at lower doses and gradually increase to the higher dose of 25.0 mg, adding to the variability in starting doses.

Patients with eGFR < 30 mL/min/1.73 m² make it difficult to determine any potential benefit in this population. The EMPA-KIDNEY trial demonstrated that the benefits of empagliflozin treatment were consistent among patients with or without DM and regardless of eGFR at randomization.⁹ Furthermore, many veterans had an initial HbA_1c levels outside the inclusion criteria range, which was a factor in the smaller sample size.

Conclusions

While the reduction in HbA_1c levels was less in patients with stage 3b CKD compared to patients stage 3a CKD, all patients experienced a benefit. The overall incidence of ADRs was low in the study population, showing empagliflozin as a favorable choice for those with T2DM and CKD. Based on the findings of this study, empagliflozin is a potentially beneficial option for reducing HbA_1c levels in patients with CKD.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Lichenoid drug eruptions are lichen planus–like hypersensitivity reactions induced by medications. These reactions are rare but cause irritation to the skin, as extreme pruritus is common. One review of 300 consecutive cases of drug eruptions submitted to dermatopathology revealed that 12% of cases were classified as lichenoid drug reactions.¹ Lichenoid dermatitis is characterized by extremely pruritic, scaly, eczematous or psoriasiform papules, often along the extensor surfaces and trunk.² The pruritic nature of the rash can negatively impact quality of life. Treatment typically involves discontinuation of the offending medication, although complete resolution can take months, even after the drug is stopped. Although there have been some data suggesting that topical and/or oral corticosteroids can help with resolution, the rash can persist even with steroid treatment.²

The histopathologic findings of lichenoid drug eruptions show lichen planus–like changes such as hyperkeratosis, irregular acanthosis, and lichenoid interface dermatitis. Accordingly, idiopathic lichen planus is an important differential diagnosis for lichenoid drug eruptions; however, compared to idiopathic lichen planus, lichenoid drug eruptions are more likely to be associated with eosinophils and parakeratosis.^1,3 In some cases, the histopathologic distinction between the 2 conditions is impossible, and clinical history needs to be considered to make a diagnosis.¹ Drugs known to cause lichenoid drug reactions more commonly include angiotensin-converting enzyme inhibitors, beta blockers, thiazides, gold, penicillamine, and antimalarials.² Lichenoid drug eruptions also have been documented in patients taking the second-generation nonsteroidal androgen receptor antagonist enzalutamide, which is used for the treatment of prostate cancer.⁴ More recently, the newer second-generation nonsteroidal androgen receptor antagonist apalutamide has been implicated in several cases of lichenoid drug eruptions.^5,6

We present a case of an apalutamide-induced lichenoid drug eruption that was resistant to dose reduction and required discontinuation of treatment due to the negative impact on the patient’s quality of life. Once the rash resolved, the patient transitioned to enzalutamide without any adverse events (AEs).

A 72-year-old man with a history of metastatic prostate cancer (stage IVB) presented to the dermatology clinic with a 4-month history of a dry itchy rash on the face, chest, back, and legs that had developed 2 to 3 months after oncology started him on apalutamide. The patient initially received apalutamide 240 mg/d, which was reduced by his oncologist 3 months later to 180 mg/d following the appearance of the rash. Then apalutamide was held as he awaited improvement of the rash.

One week after the apalutamide was held, the patient presented to dermatology. He reported that he had tried over-the-counter ammonium lactate 12% lotion twice daily when the rash first developed without improvement. When the apalutamide was held, oncology prescribed mupirocin ointment 2% 3 times daily which yielded minimal relief. On physical examination, widespread lichenified papules and plaques were noted on the face, chest, back, and legs (Figure 1). Dermatology initially prescribed triamcinolone ointment 0.1% twice daily. A 4-mm punch biopsy specimen of the upper back revealed a lichenoid interface dermatitis with numerous eosinophils compatible with a lichenoid hypersensitivity reaction (Figure 2). Considering the clinical and histologic findings, a diagnosis of lichenoid drug eruption secondary to apalutamide treatment was made.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

To the Editor:

Scleroderma is a chronic autoimmune connective tissue disease that results in excessive collagen deposition in the skin and other organs throughout the body. On its own or in the setting of mixed connective tissue disease, scleroderma can result in systemic or localized symptoms that can limit patients’ functional capabilities, cause pain and discomfort, and reduce self-esteem—all negatively impacting patients’ quality of life.^1,2 Neck sclerosis is a common manifestation of scleroderma. There is no curative treatment for scleroderma; thus, therapy is focused on slowing disease progression and improving quality of life. We present a case of neck sclerosis in a 44-year-old woman with scleroderma that was successfully treated with botulinum toxin (BTX) type A injection, resulting in improved skin laxity and appearance with high patient satisfaction. Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region.

A 44-year-old woman presented to the dermatology clinic for treatment of thickened neck skin with stiffness and tightness that had been present for months to years. She had a history of mixed connective tissue disease (MCTD)(positive anti-ribonucleoprotein, anti–Sjögren syndrome–related antigen, and anti-Smith antibodies) with features of scleroderma and polyarthritis. The patient currently was taking sulfasalazine for the polyarthritis; she previously had taken hydroxychloroquine but discontinued treatment due to ineffectiveness. She was not taking any topical or systemic medications for scleroderma. On physical examination, the skin on the anterior neck appeared thickened with shiny patches (Figure 1). Pinching the skin in the affected area demonstrated ­sclerosis with high tension.

Scleroderma is a chronic connective tissue disorder that results in excessive collagen deposition in the skin and other organs throughout the body.⁴ Although the etiology is unknown, scleroderma develops when overactivation of the immune system leads to CD4⁺ T-lymphocyte infiltration in the skin, along with the release of profibrotic interleukins and growth factors, resulting in fibrosis.⁴ Subtypes include localized scleroderma (morphea), limited cutaneous systemic sclerosis (formerly known as CREST [calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia] syndrome), diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma.⁵ Scleroderma is associated with positive antinuclear antibodies and HLA II alleles (HLA-DR2 and HLA-DR5).

On its own or in the setting of MCTD, scleroderma can result in systemic or localized symptoms. Overall, the most common symptom is RP.⁵ Localized scleroderma and limited cutaneous systemic sclerosis manifest with symptoms of the skin and underlying tissues. Diffuse cutaneous systemic sclerosis involves cutaneous and visceral symptoms, including lung, esophageal, and vascular involvement.⁶ Similar to MCTD, scleroderma is most prevalent in middle-aged females,⁷ though it occurs at a higher rate and with a more severe disease course in Black patients.⁸

A highly sensitive and specific test for scleroderma that can aid in diagnosis is the neck sign—tightening of the skin of the neck when the head extends.^9,10 In one study, the neck sign was positive in more than 90% of patients with scleroderma and negative for control patients and those with primary RP.⁹ Thus, neck sclerosis is a common manifestation of scleroderma for which patients may seek treatment.

While there is no curative treatment for scleroderma, skin manifestations can be treated with mycophenolate mofetil or methotrexate.⁵ Systemic treatments may be recommended if the patient has additional symptoms, such as azathioprine for myositis/arthritis and cyclophosphamide for interstitial lung disease.⁵ However, it is important to note that these medications are associated with risk for gastrointestinal upset, mouth sores, fatigue, or other complications.

Botulinum toxin is a bacterial protein toxin and neuromodulator that inhibits neurotransmitter release by cleaving SNARE proteins at peripheral nerve terminal junctions.¹¹ It has been used in a variety of dermatologic and nondermatologic conditions, including migraines, hyperhidrosis, contractures, scars, and overactive bladder. It also has been used in aesthetics for facial rejuvenation and minimization of wrinkle appearance. Dermatologists and rheumatologists have successfully used BTX to treat primary and secondary RP—the most common symptom of scleroderma—due to its vasodilatation properties.¹² Although our patient did not have RP, use of BTX to treat other features of scleroderma, including en coup de sabre, thoracic outlet syndrome, dyspareunia, gastroparesis, pterygium inversum unguis, and dysphagia has been documented.^13-18 An in vivo mouse study that examined the possible mechanism for BTX as a treatment in scleroderma found that BTX injections significantly decreased dermal thickness and inflammation in fibrosis (P<.05). An analysis of oxidative stress and mRNA expression showed that BTX may treat fibrosis by suppressing oxidative stress and inflammatory cells, resulting in decreased apoptosis and oxidant-induced intracellular accumulation of reactive oxygen species.¹⁹ Another animal study demonstrated the positive effects of BTX treatment for fibrosis of the bladder in rats.²⁰ In one case report, a female patient with scleroderma and facial fibrosis received perioral BTX injections for cosmetic purposes but also observed improvement in mouth constriction, demonstrating the potential efficacy of BTX for facial fibrosis.²¹

Our case demonstrates the potential positive effects of BTX treatment in patients with features of sclerosis or fibrosis, particularly in the neck region. We recommend assessing the efficacy of the initial BTX treatment after 2 to 3 weeks, with additional injections as needed to achieve the patient’s desired level of comfort and appearance at approximately 3-month intervals (aligning with the expected duration of efficacy of BTX).²² Our patient experienced considerable relief and high satisfaction with BTX treatment. Given the limitations of sclerosis treatments and the unwanted adverse-effect profile of systemic treatments, BTX injections may be a preferrable treatment option for cutaneous manifestations of ­scleroderma among patients. Future studies with larger patient populations and a control group are warranted to further explore the use of BTX for the dermatologic treatment of scleroderma.

THE DIAGNOSIS: Acral Hemorrhagic Darier Disease

Darier disease (DD), also known as keratosis follicularis, is a rare autosomal-dominant genodermatosis caused by mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene (ATP2A2). This gene encodes the enzyme sarcoplasmic/endoplasmic reticulum calcium ATPase 2, which results in abnormal calcium signaling in keratinocytes and leads to dyskeratosis.¹ Darier disease commonly manifests in the second decade of life with hyperkeratotic papules coalescing into plaques, often accompanied by erosions and fissures that cause discomfort and pruritus. Darier disease also is associated with characteristic nail findings such as the classic candy cane nails and V-shaped nicking.

Acral hemorrhagic lesions are a rare manifestation of DD. Clinically, these lesions can manifest as hemorrhagic macules, papules, and/or vesicles, most commonly occurring following local trauma or retinoid use. Patients with these lesions are believed to have either specific mutations in the ATP2A2 gene that impair sarcoplasmic/endoplasmic reticulum calcium ATPase 2 function in the vascular endothelium or a mutation in the sarcoplasmic/endoplasmic reticulum calcium ATPase protein itself, leading to dysregulation of mitochondrial homeostasis from within the cell, provoking oxidative stress and causing detrimental effects on blood vessels.² Patients with this variant can present with all the features of classic DD concomitantly, with varying symptom severity or distinct clinical features during separate episodic flares, or as the sole manifestation. Other nonclassical lesions of DD include acral keratoderma, giant comedones, keloidlike vegetations, and leucodermic macules (Figure).³

Acral hemorrhagic DD may appear either in isolation or in tandem with more traditional symptoms, necessitating consideration of other possible differential diagnoses such as acrokeratosis verruciformis of Hopf (AKV), porphyria cutanea tarda, bullous lichen planus (BLP), and hemorrhagic lichen sclerosus.

Sometimes regarded as a variant of DD, AKV is an autosomal- dominant genodermatosis characterized by flat or verrucous hyperkeratotic papules on the hands and feet. In AKV, the nails also may be affected, with changes including striations, subungual hyperkeratosis, and V-shaped nicking of the distal nails. Although our patient displayed features of AKV, it has not been associated with acral hemorrhagic macules, making this diagnosis less likely than DD.⁴

Porphyria cutanea tarda, a condition caused by decreased levels of uroporphyrinogen decarboxylase, also can cause skin manifestations such as blistering as well as increased skin fragility, predominantly in sun-exposed areas.⁵ Our patient’s lack of photosensitivity and absence of other common symptoms of this disorder, such as hypertrichosis and hyperpigmentation, made porphyria cutanea tarda less likely.

Bullous lichen planus is a rare subtype of lichen planus characterized by tense bullae arising from preexisting lichen planus lesions or appearing de novo, most commonly manifesting on the oral mucosa or the legs.⁶ The bullae associated with BLP can rupture and form ulcers—a symptom that could potentially be mistaken for hemorrhagic macules like the ones observed in our patient. However, BLP typically is characterized by erythematous, violaceous, polygonal papules commonly appearing on the oral mucosa and the legs with blisters developing near or on pre-existing lichen planus lesions. These are different from the hyperkeratotic papules and leucodermic macules seen in our patient, which aligned more closely with the clinical presentation of DD.

Hemorrhagic lichen sclerosus presents with white atrophic patches and plaques and hemorrhagic bullae, which may resemble the leucodermic macules and hemorrhagic macules of DD. However, hemorrhagic lichen sclerosus most commonly involves the genital area in postmenopausal women. Extragenital manifestations of lichen sclerosus, although less common, can occur and typically manifest on the thighs, buttocks, breasts, back, chest, axillae, shoulders, and wrists.⁷ Notably, these hemorrhagic lesions typically are surrounded by hypopigmented skin and display an atrophic appearance.

Management of DD can be challenging. General measures include sun protection, heat avoidance, and friction reduction. Retinoids are considered the first-line therapy for severe DD, as they help normalize keratinocyte differentiation and reduce keratotic scaling.⁸ Topical corticosteroids can help manage inflammation and reduce the risk for secondary infections. Our patient responded well to this treatment approach, with a notable reduction in the number and severity of the hyperkeratotic plaques and resolution of the acral hemorrhagic lesions.

THE DIAGNOSIS: Acral Hemorrhagic Darier Disease

Darier disease (DD), also known as keratosis follicularis, is a rare autosomal-dominant genodermatosis caused by mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene (ATP2A2). This gene encodes the enzyme sarcoplasmic/endoplasmic reticulum calcium ATPase 2, which results in abnormal calcium signaling in keratinocytes and leads to dyskeratosis.¹ Darier disease commonly manifests in the second decade of life with hyperkeratotic papules coalescing into plaques, often accompanied by erosions and fissures that cause discomfort and pruritus. Darier disease also is associated with characteristic nail findings such as the classic candy cane nails and V-shaped nicking.

Acral hemorrhagic lesions are a rare manifestation of DD. Clinically, these lesions can manifest as hemorrhagic macules, papules, and/or vesicles, most commonly occurring following local trauma or retinoid use. Patients with these lesions are believed to have either specific mutations in the ATP2A2 gene that impair sarcoplasmic/endoplasmic reticulum calcium ATPase 2 function in the vascular endothelium or a mutation in the sarcoplasmic/endoplasmic reticulum calcium ATPase protein itself, leading to dysregulation of mitochondrial homeostasis from within the cell, provoking oxidative stress and causing detrimental effects on blood vessels.² Patients with this variant can present with all the features of classic DD concomitantly, with varying symptom severity or distinct clinical features during separate episodic flares, or as the sole manifestation. Other nonclassical lesions of DD include acral keratoderma, giant comedones, keloidlike vegetations, and leucodermic macules (Figure).³

Acral hemorrhagic DD may appear either in isolation or in tandem with more traditional symptoms, necessitating consideration of other possible differential diagnoses such as acrokeratosis verruciformis of Hopf (AKV), porphyria cutanea tarda, bullous lichen planus (BLP), and hemorrhagic lichen sclerosus.

Sometimes regarded as a variant of DD, AKV is an autosomal- dominant genodermatosis characterized by flat or verrucous hyperkeratotic papules on the hands and feet. In AKV, the nails also may be affected, with changes including striations, subungual hyperkeratosis, and V-shaped nicking of the distal nails. Although our patient displayed features of AKV, it has not been associated with acral hemorrhagic macules, making this diagnosis less likely than DD.⁴

Porphyria cutanea tarda, a condition caused by decreased levels of uroporphyrinogen decarboxylase, also can cause skin manifestations such as blistering as well as increased skin fragility, predominantly in sun-exposed areas.⁵ Our patient’s lack of photosensitivity and absence of other common symptoms of this disorder, such as hypertrichosis and hyperpigmentation, made porphyria cutanea tarda less likely.

Bullous lichen planus is a rare subtype of lichen planus characterized by tense bullae arising from preexisting lichen planus lesions or appearing de novo, most commonly manifesting on the oral mucosa or the legs.⁶ The bullae associated with BLP can rupture and form ulcers—a symptom that could potentially be mistaken for hemorrhagic macules like the ones observed in our patient. However, BLP typically is characterized by erythematous, violaceous, polygonal papules commonly appearing on the oral mucosa and the legs with blisters developing near or on pre-existing lichen planus lesions. These are different from the hyperkeratotic papules and leucodermic macules seen in our patient, which aligned more closely with the clinical presentation of DD.

Hemorrhagic lichen sclerosus presents with white atrophic patches and plaques and hemorrhagic bullae, which may resemble the leucodermic macules and hemorrhagic macules of DD. However, hemorrhagic lichen sclerosus most commonly involves the genital area in postmenopausal women. Extragenital manifestations of lichen sclerosus, although less common, can occur and typically manifest on the thighs, buttocks, breasts, back, chest, axillae, shoulders, and wrists.⁷ Notably, these hemorrhagic lesions typically are surrounded by hypopigmented skin and display an atrophic appearance.

Management of DD can be challenging. General measures include sun protection, heat avoidance, and friction reduction. Retinoids are considered the first-line therapy for severe DD, as they help normalize keratinocyte differentiation and reduce keratotic scaling.⁸ Topical corticosteroids can help manage inflammation and reduce the risk for secondary infections. Our patient responded well to this treatment approach, with a notable reduction in the number and severity of the hyperkeratotic plaques and resolution of the acral hemorrhagic lesions.

THE DIAGNOSIS: Acral Hemorrhagic Darier Disease

Darier disease (DD), also known as keratosis follicularis, is a rare autosomal-dominant genodermatosis caused by mutations in the ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 gene (ATP2A2). This gene encodes the enzyme sarcoplasmic/endoplasmic reticulum calcium ATPase 2, which results in abnormal calcium signaling in keratinocytes and leads to dyskeratosis.¹ Darier disease commonly manifests in the second decade of life with hyperkeratotic papules coalescing into plaques, often accompanied by erosions and fissures that cause discomfort and pruritus. Darier disease also is associated with characteristic nail findings such as the classic candy cane nails and V-shaped nicking.

Acral hemorrhagic lesions are a rare manifestation of DD. Clinically, these lesions can manifest as hemorrhagic macules, papules, and/or vesicles, most commonly occurring following local trauma or retinoid use. Patients with these lesions are believed to have either specific mutations in the ATP2A2 gene that impair sarcoplasmic/endoplasmic reticulum calcium ATPase 2 function in the vascular endothelium or a mutation in the sarcoplasmic/endoplasmic reticulum calcium ATPase protein itself, leading to dysregulation of mitochondrial homeostasis from within the cell, provoking oxidative stress and causing detrimental effects on blood vessels.² Patients with this variant can present with all the features of classic DD concomitantly, with varying symptom severity or distinct clinical features during separate episodic flares, or as the sole manifestation. Other nonclassical lesions of DD include acral keratoderma, giant comedones, keloidlike vegetations, and leucodermic macules (Figure).³

Acral hemorrhagic DD may appear either in isolation or in tandem with more traditional symptoms, necessitating consideration of other possible differential diagnoses such as acrokeratosis verruciformis of Hopf (AKV), porphyria cutanea tarda, bullous lichen planus (BLP), and hemorrhagic lichen sclerosus.

Sometimes regarded as a variant of DD, AKV is an autosomal- dominant genodermatosis characterized by flat or verrucous hyperkeratotic papules on the hands and feet. In AKV, the nails also may be affected, with changes including striations, subungual hyperkeratosis, and V-shaped nicking of the distal nails. Although our patient displayed features of AKV, it has not been associated with acral hemorrhagic macules, making this diagnosis less likely than DD.⁴

Porphyria cutanea tarda, a condition caused by decreased levels of uroporphyrinogen decarboxylase, also can cause skin manifestations such as blistering as well as increased skin fragility, predominantly in sun-exposed areas.⁵ Our patient’s lack of photosensitivity and absence of other common symptoms of this disorder, such as hypertrichosis and hyperpigmentation, made porphyria cutanea tarda less likely.

Bullous lichen planus is a rare subtype of lichen planus characterized by tense bullae arising from preexisting lichen planus lesions or appearing de novo, most commonly manifesting on the oral mucosa or the legs.⁶ The bullae associated with BLP can rupture and form ulcers—a symptom that could potentially be mistaken for hemorrhagic macules like the ones observed in our patient. However, BLP typically is characterized by erythematous, violaceous, polygonal papules commonly appearing on the oral mucosa and the legs with blisters developing near or on pre-existing lichen planus lesions. These are different from the hyperkeratotic papules and leucodermic macules seen in our patient, which aligned more closely with the clinical presentation of DD.

Hemorrhagic lichen sclerosus presents with white atrophic patches and plaques and hemorrhagic bullae, which may resemble the leucodermic macules and hemorrhagic macules of DD. However, hemorrhagic lichen sclerosus most commonly involves the genital area in postmenopausal women. Extragenital manifestations of lichen sclerosus, although less common, can occur and typically manifest on the thighs, buttocks, breasts, back, chest, axillae, shoulders, and wrists.⁷ Notably, these hemorrhagic lesions typically are surrounded by hypopigmented skin and display an atrophic appearance.

Management of DD can be challenging. General measures include sun protection, heat avoidance, and friction reduction. Retinoids are considered the first-line therapy for severe DD, as they help normalize keratinocyte differentiation and reduce keratotic scaling.⁸ Topical corticosteroids can help manage inflammation and reduce the risk for secondary infections. Our patient responded well to this treatment approach, with a notable reduction in the number and severity of the hyperkeratotic plaques and resolution of the acral hemorrhagic lesions.

As large-scale natural disasters become more common, health care coalitions and the engagement of health systems with local, state, and federal public health departments have effectively bolstered communities’ resilience via collective sharing and distribution of resources.¹ These resources may include supplies and the dissemination of emergency information, education, and training.² The COVID-19 pandemic demonstrated that larger health care systems including hospital networks and nursing homes are better connected to health care coalition resources than smaller, independent systems, such as community home health agencies.³ This leaves some organizations on their own to meet requirements that maintain continuity of care and support their patients and staff throughout a natural disaster.

Home health care workers play important roles in the care of older adults.⁴ Older adults experience high levels of disability and comorbidities that put them at risk during emergencies; they often require support from paid, family, and neighborhood caregivers to live independently.⁵ More than 9.3 million US adults receive paid care from 2.6 million home health care workers (eg, home health aides and personal care assistants).⁶ Many of these individuals are hired through small independent home health agencies (HHAs), while others may work directly for an individual. When neighborhood resources and family caregiving are disrupted during emergencies, the critical services these workers administer become even more essential to ensuring continued access to medical care and social services.

The importance of these services was underscored by the Centers for Medicare and Medicaid Services 2017 inclusion of HHAs in federal emergency preparedness guidelines.^7,8 The fractured and decentralized nature of the home health care industry means many HHAs struggle to maintain continuous care during emergencies and protect their staff. HHAs, and health care workers in the home, are often isolated, under-resourced, and disconnected from broader emergency planning efforts. Additionally, home care jobs are largely part-time, unstable, and low paying, making the workers themselves vulnerable during emergencies.^3,9-13

This is a significant issue for the Veterans Health Administration (VHA), which annually purchases 10.5 million home health care worker visits for 150,000 veterans from community-based HHAs to enable those individuals to live independently. Figure 1 illustrates the existing structure of directly provided and contracted VHA services for community-dwelling veterans, highlighting the circle of care around the veteran.^8,9 Home health care workers anchored health care teams during the COVID-19 pandemic, observing and reporting on patients’ well-being to family caregivers, primary care practitioners, and HHAs. They also provided critical emotional support and companionship to patients isolated from family and friends.⁹ These workers also exposed themselves and their families to considerable risk and often lacked the protection afforded by personal protective equipment (PPE) in accordance with infection prevention guidance.^3,12

Through a combination of its national and local health care networks, the VHA has a robust and well-positioned emergency infrastructure to supportcommunity-dwelling older adults during disasters.¹⁴ This network is supported by the VHA Office of Emergency Management, which shares resources and guidance with local emergency managers at each facility as well as individual programs such as the VHA Home Based Primary Care (HBPC) program, which provides 38,000 seriously ill veterans with home medical visits.¹⁵ Working closely with their local and national hospital networks and emergency managers, individual VHA HBPC programs were able to maintain the safety of staff and continuity of care for patients enrolled in HBPC by rapidly administering COVID-19 vaccines to patients, caregivers, and staff, and providing emergency assistance during the 2017 hurricane season.^16,17 These efforts were successful because HBPC practitioners and their patients, had access to a level of emergency-related information, resources, and technology that are often out of reach for individual community-based health care practitioners (HCPs). The US Department of Veterans Affairs (VA) also supports local communities through its Fourth Mission, which provides emergency resources to non-VHA health care facilities (ie, hospitals and nursing homes) during national emergencies and natural disasters.¹⁷ Although there has been an expansion in the definition of shared resources, such as extending behavioral health support to local communities, the VHA has not historically provided these resources to HHAs.¹⁴

This study examines opportunities to leverage VHA emergency management resources to support contracted HHAs and inform other large health system emergency planning efforts. The findings from the exploratory phase are described in this article. We interviewed VHA emergency managers, HBPC and VA staff who coordinate home health care worker services, as well as administrators at contracted HHAs within a Veterans Integrated Services Network (VISN). These findings will inform the second (single-site pilot study) and third (feasibility study) phases. Our intent was to (1) better understand the relationships between VA medical centers (VAMCs) and their contracted HHAs; (2) identify existing VHA emergency protocols to support community-dwelling older adults; and (3) determine opportunities to build on existing infrastructure and relationships to better support contracted HHAs and their staff in emergencies.

Methods

The 18 VISNs act as regional systems of care that are loosely connected to better meet local health needs and maximize access to care. This study was conducted at 6 of 9 VAMCs within VISN 2, the New York/New Jersey VHA Health Care Network.¹⁸ VAMCs that serve urban, rural, and mixed urban/rural catchment areas were included.

Each VAMC has an emergency management program led by an emergency manager, an HBPC program led by a program director and medical director, and a community care or purchased care office that has a liaison who manages contracted home health care worker services. The studyfocused on HBPC programs because they are most likely to interact with veterans’ home health care workers in the home and care for community-dwelling veterans during emergencies. Each VHA also contracts with a series of local HHAs that generally have a dedicated staff member who interfaces with the VHA liaison. Our goal was to interview ≥ 1 emergency manager, ≥ 1 HBPC team member, ≥ 1 community care staff person, and ≥ 1 contracted home health agency administrator at each site to gain multiple perspectives from the range of HCPs serving veterans in the community.

Recruitment and Data Collection

The 6 sites were selected in consultation with VISN 2 leadership for their strong HBPC and emergency management programs. To recruit respondents, we contacted VISN and VAMC leads and used our professional networks to identify a sample of multidisciplinary individuals who represent both community care and HBPC programs who were contacted via email.

Since each VAMC is organized differently, we utilized a snowball sampling approach to identify the appropriate contacts.¹⁹ At the completion of each interview, we asked the participant to suggest additional contacts and introduce us to any remaining stakeholders (eg, the emergency manager) at that site or colleagues at other VISN facilities. Because roles vary among VAMCs, we contacted the person who most closely resembled the identified role and asked them to direct us to a more appropriate contact, if necessary. We asked community care managers to identify 1 to 2 agencies serving the highest volume of patients who are veterans at their site and requested interviews with those liaisons. This resulted in the recruitment of key stakeholders from 4 teams across the 6 sites (Table).

A semistructured interview guide was jointly developed based on constructs of interest, including relationships within VAMCs and between VAMCs and HHAs; existing emergency protocols and experience during disasters; and suggestions and opportunities for supporting agencies during emergencies and potential barriers. Two researchers (TWL and EF) who were trained in qualitative methods jointly conducted interviews using the interview guide, with 1 researcher leading and another taking notes and asking clarifying questions.

Interviews were conducted virtually via Microsoft Teams with respondents at their work locations between September 2022 and January 2023. Interviews were audio recorded and transcribed and 2 authors (TWL and ESO) reviewed transcripts for accuracy. Interviews averaged 47 minutes in length (range, 20-59).

The study was reviewed and determined to be exempt by institutional review boards at the James J. Peters VAMC and Greater Los Angeles VAMC. We asked participants for verbal consent to participate and preserved their confidentiality.

Analysis

Data were analyzed via an inductive approach, which involves drawing salient themes rather than imposing preconceived theories.²⁰ Three researchers (TWL, EF, and ES) listened to and discussed 2 staff interviews and tagged text with specific codes (eg, communication between the VHA and HHA, internal communication, and barriers to case fulfillment) so the team could selectively return to the interview text for deeper analysis, allowing for the development of a final codebook. The project team synthesized the findings to identify higher-level themes, drawing comparisons across and within the respondent groups, including within and between health care systems. Throughout the analysis, we maintained analytic memos, documented discussions, and engaged in analyst triangulation to ensure trustworthiness.^21,22 To ensure the analysis accurately reflected the participants’ understanding, we held 2 virtual member-checking sessions with participants to share preliminary findings and conclusions and solicit feedback. Analysis was conducted using ATLAS.ti version 20.

Results

VHA-based participants described internal emergency management systems that are deployed during a disaster to support patients and staff. Agency participants described their own internal emergency management protocols. Respondents discussed how and when the 2 intersected, as well as opportunities for future mutual support. The analysis identified several themes: (1) relationships between VAMC teams; (2) relationships between VHA and HHAs; (3) VHA and agencies responses during emergencies; (4) receptivity and opportunities for extending VHA resources into the community; and (5) barriers and facilitators to deeper engagement.

Relationships Within VHA (n = 17)

Staff at all VHA sites described close relationships between the internal emergency management and HBPC teams. HBPC teams identified patients who were most at risk during emergencies to triage those with the highest medical needs (eg, patients dependent on home infusion, oxygen, or electronic medical devices) and worked alongside emergency managers to develop plans to continue care during an emergency. HBPC representatives were part of their facilities’ local emergency response committees. Due to this close collaboration, VHA emergency managers were familiar with the needs of homebound veterans and caregivers. “I invite our [HBPC] program manager to attend [committee] meetings and … they’re part of the EOC [emergency operations center]," an emergency manager said. “We work together and I’m constantly in contact with that individual, especially during natural disasters and so forth, to ensure that everybody’s prepared in the community.”

On the other hand, community caremanagers—who described frequent interactions with HBPC teams, largely around coordinating and managing non-VHA home care services—were less likely to have direct relationships with their facility emergency managers. For example, when asked if they had a relationship with their emergency manager, a community care manager admitted, “I [only] know who he is.” They also did not report having structured protocols for veteran outreach during emergencies, “because all those veterans who are receiving [home health care worker] services also belong to a primary care team,” and considered the outreach to be the responsibility of the primary care team and HHA.

Relationships Between the VHA and HHAs (n = 17)

Communication between VAMCs and contracted agencies primarily went through community care managers, who described established long-term relationships with agency administrators. Communication was commonly restricted to operational activities, such as processing referrals and occasional troubleshooting. According to a community care manager most communication is “why haven’t you signed my orders?” There was a general sense from participants that communication was promptly answered, problems were addressed, and professional collegiality existed between the agencies as patients were referred and placed for services. One community care manager reported meeting with agencies regularly, noting, “I talk to them pretty much daily.”

If problems arose, community care managers described themselves as “the liaison” between agencies and VHA HCPs who ordered the referrals. This is particularly the case if the agency needed help finding a VHA clinician or addressing differences in care delivery protocols.

Responding During Emergencies (n = 19)

During emergencies, VHA and agency staff described following their own organization’s protocols and communicating with each other only on a case-by-case basis rather than through formal or systematic channels and had little knowledge of their counterpart’s emergency protocols. Beyond patient care, there was no evidence of information sharing between VHA and agency staff. Regarding sharing information with their local community, an HBPC Program Director said, “it’s almost like the VHA had become siloed” and operated on its own without engaging with community health systems or emergency managers.

Beyond the guidance provided by state departments of public health, HHAs described collaborating with other agencies in their network and relying on their informal professional network to manage the volume of information and updates they followed during emergencies like the COVID-19 pandemic. One agency administrator did not frequently communicate with VHA partners during the pandemic but explained that the local public health department helped work through challenges. However, “we realized pretty quickly they were overloaded and there was only so much they could do.” The agency administrator turned to a “sister agency” and local hospitals, noting, “Wherever you have connections in the field or in the industry, you know you’re going to reach out to people for guidance on policies and… protocol.”

Opportunities for Extending VHA Resources to the Community (n = 16)

All VHA emergency managers were receptive to extending support to community-based HCPS and, in some cases, felt strongly that they were an essential part of veterans’ care networks. Emergency managers offered examples for how they supportedcommunity-based HCPs, such as helping those in the VAMC medical foster home program develop and evaluate emergency plans. Many said they had not explicitly considered HHAs before (Appendix).

Emergency managers also described how supporting community-based HCPs could be considered within the scope of the VHA role and mission, specifically the Fourth Mission. “I think that we should be making our best effort to make sure that we’re also providing that same level [of protection] to the people taking care of the veteran [as our VHA staff],” an emergency manager said. “It’s our responsibility to provide the best for the staff that are going into those homes to take care of that patient.”

In many cases, emergency managers had already developed practical tools that could be easily shared outside the VHA, including weather alerts, trainings, emergency plan templates, and lists of community resources and shelters (Figure 2). A number of these examples built on existing communication channels. One emergency manager said that the extension of resources could be an opportunity to decrease the perceived isolation of home health care workers through regular training for agencies that are providing health care aides, so that they know that “some bigger folks are keeping an eye on it.”

On the agency side, participants noted that some HHAs could benefit more from support than others. While some agencies are well staffed and have good protocols and keep up to date, “There are smaller agencies, agencies that are starting up that may not have the resources to just disseminate all the information. Those are the agencies [that] could well benefit from the VHA,” an HBPC medical director explained. Agency administrators suggested several areas where they would welcome support, including a deeper understanding of available community resources and access to PPE for staff. Regarding informational resources, an administrator said, “Anytime we can get information, it’s good to have it come to you and not always have to go out searching for it.”

Barriers and Facilitators to Partnering With Community Agencies (n = 16)

A primary barrier regarding resource sharing was potential misalignment between each organization’s policies. HHAs followed state and federal public health guidelines, which sometimes differed from VHA policies. Given that agencies care for both VHA and non-VHA clients, questions also arose around how agencies would prioritize information from the VHA, if they were already receiving information from other sources. When asked about information sharing, both VHA staff and agencies agreed staff time to support any additional activities should be weighed against the value of the information gained.

Six participants also shared that education around emergency preparedness could be an opportunity to bridge gaps between VAMCs and their surrounding communities. One local Chief of Community Care noted, “Any opportunity to just give information is going to make it a lot better for the veteran patient … to have something that’s a little more robust.”

Two emergency managers noted the need to be sensitive in the way they engaged with partners, respecting and building on the work that agencies were already doing in this area to ensure VHA was seen as a trusted partner and resource rather than trying to impose new policies or rules on community-based HCPs. “I know that like all leadership in various organizations, there’s a little bit of bristling going on when other people try and tell them what to do,” an HBPC medical director said. “However, if it is established that as a sort of greater level like a state level or a federal level, that VHA can be a resource. I think that as long as that’s recognized by their own professional organizations within each state, then I think that that would be a tremendous advantage to many agencies.”

In terms of sharing physical resources, emergency managers raised concerns around potential liability, although they also acknowledged this issue was important enough to think about potential workarounds. As one emergency manager said, “I want to know that my PPE is not compromised in any way shape or form and that I am in charge of that PPE, so to rely upon going to a home and hoping that [the PPE] wasn’t compromised … would kind of make me a little uneasy.” This emergency manager suggested possible solutions, such as creating a sealed PPE package to give directly to an aide.

Discussion

As the prevalence of climate-related disasters increases, the need to ensure the safety and independence of older adults during emergencies grows more urgent. Health systems must think beyond the direct services they provide and consider the community resources upon which their patients rely. While relationships did not formally exist between VHA emergency managers and community home health HCPs in the sample analyzed in this article, there is precedent and interest in supporting contracted home health agencies caring for veterans in the community. Although not historically part of the VA Fourth Mission, creating a pipeline of support for contracted HHAs by leveraging existing relationships and resources can potentially strengthen its mission to protect older veterans in emergencies, help them age safely in place, and provide a model for health systems to collaborate with community-based HCPs around emergency planning and response (Figure 3).²³

Existing research on the value of health care coalitions highlights the need for established and growing partnerships with a focus on ensuring they are value-added, which echoes concerns we heard in interviews.²⁴ Investment in community partnerships not only includes sharing supplies but also relying on bidirectional support that can be a trusted form of timely information.^1,25 The findings in this study exhibit strong communication practices within the VHA during periods of nonemergency and underscore the untapped value of the pre-existing relationship between VAMCs and their contracted HHAs as an area of potential growth for health care coalitions.

Sharing resources in a way that does not put new demands on partners contributes to the sustainability and value-added nature of coalitions. Examples include establishing new low-investment practices (ie, information sharing) that support capacity and compliance with existing requirements rather than create new responsibilities for either member of the coalition. The relationship between the VHA emergency managers and the VHA HBPC program can act as a guide. The emergency managers interviewed for this study are currently engaged with HBPC programs and therefore understand the needs of homebound older adults and their caregivers. Extending the information already available to the HBPC teams via existing channels strengthens workforce practices and increased security for the shared patient, even without direct relationships between emergency managers and agencies. It is important to understand the limitations of these practices, including concerns around conflicting federal and state mandates, legal concerns around the liability of sharing physical resources (such as PPE), and awareness that the objective is not for the VHA to increase burdens (eg, increasing compliance requirements) but rather to serve as a resource for a mutual population in a shared community.

Offering training and practical resources to HHA home health care workers can help them meet disaster preparedness requirements. This is particularly important considering the growing home care workforce shortages, a topic mentioned by all HBPC and community care participants interviewed for this study.^26,27 Home health care workers report feeling underprepared and isolated while on the job in normal conditions, a sentiment exacerbated by the COVID-19 pandemic.^3,10 Supporting these individuals may help them feel more prepared and connected to their work, improving stability and quality of care.

While these issues are priorities within the VHA, there is growing recognition at the state and federal level of the importance of including older adults and their HCPs in disaster preparedness and response.^5,28 The US Department of Health and Human Services, for example, includes older adults and organizations that serve them on its National Advisory Committee on Seniors and Disasters. The Senate version of the 2023 reauthorization of the Pandemic and All-Hazards Preparedness and Response Act included specific provisions to support community-dwelling older adults and people with disabilities, incorporating funding for community organizations to support continuity of services and avoid institutionalization in an emergency.²⁹ Other proposed legislation includes the Real Emergency Access for Aging and Disability Inclusion for Disasters Act, which would ensure the needs of older adults and people with disabilities are explicitly included in all phases of emergency planning and response.³⁰

The VHA expansion of the its VEText program to include disaster response is an effort to more efficiently extend outreach to older and vulnerable patients who are veterans.³¹ Given these growing efforts, the VHA and other health systems have an opportunity to expand internal emergency preparedness efforts to ensure the health and safety of individuals living in the community.

Limitations

VISN 2 has been a target of terrorism and other disasters. In addition to the sites being initially recruited for their strong emergency management protocols, this context may have biased respondents who are favorable to extending their resources into the community. At the time of recruitment, contracted HHAs were still experiencing staff shortages due to the COVID-19 pandemic, which limited the ability of agency staff to participate in interviews. Additionally, while the comprehensive exploration of VISN 2 facilities allows for confidence of the organizational structures described, the qualitative research design and small study sample, the study findings cannot be immediately generalized to all VISNs.

Conclusions

Many older veterans increasingly rely on home health care workers to age safely. The VHA, as a large national health care system and leader in emergency preparedness, could play an important role in supporting home health care workers and ameliorating their sense of isolation during emergencies and natural disasters. Leveraging existing resources and relationships may be a low-cost, low-effort opportunity to build higher-level interventions that support the needs of patients. Future research and work in this field, including the authors’ ongoing work, will expand agency participation and engage agency staff in conceptualizing pilot projects to ensure they are viable and feasible for the field.

As large-scale natural disasters become more common, health care coalitions and the engagement of health systems with local, state, and federal public health departments have effectively bolstered communities’ resilience via collective sharing and distribution of resources.¹ These resources may include supplies and the dissemination of emergency information, education, and training.² The COVID-19 pandemic demonstrated that larger health care systems including hospital networks and nursing homes are better connected to health care coalition resources than smaller, independent systems, such as community home health agencies.³ This leaves some organizations on their own to meet requirements that maintain continuity of care and support their patients and staff throughout a natural disaster.

Home health care workers play important roles in the care of older adults.⁴ Older adults experience high levels of disability and comorbidities that put them at risk during emergencies; they often require support from paid, family, and neighborhood caregivers to live independently.⁵ More than 9.3 million US adults receive paid care from 2.6 million home health care workers (eg, home health aides and personal care assistants).⁶ Many of these individuals are hired through small independent home health agencies (HHAs), while others may work directly for an individual. When neighborhood resources and family caregiving are disrupted during emergencies, the critical services these workers administer become even more essential to ensuring continued access to medical care and social services.

The importance of these services was underscored by the Centers for Medicare and Medicaid Services 2017 inclusion of HHAs in federal emergency preparedness guidelines.^7,8 The fractured and decentralized nature of the home health care industry means many HHAs struggle to maintain continuous care during emergencies and protect their staff. HHAs, and health care workers in the home, are often isolated, under-resourced, and disconnected from broader emergency planning efforts. Additionally, home care jobs are largely part-time, unstable, and low paying, making the workers themselves vulnerable during emergencies.^3,9-13

This is a significant issue for the Veterans Health Administration (VHA), which annually purchases 10.5 million home health care worker visits for 150,000 veterans from community-based HHAs to enable those individuals to live independently. Figure 1 illustrates the existing structure of directly provided and contracted VHA services for community-dwelling veterans, highlighting the circle of care around the veteran.^8,9 Home health care workers anchored health care teams during the COVID-19 pandemic, observing and reporting on patients’ well-being to family caregivers, primary care practitioners, and HHAs. They also provided critical emotional support and companionship to patients isolated from family and friends.⁹ These workers also exposed themselves and their families to considerable risk and often lacked the protection afforded by personal protective equipment (PPE) in accordance with infection prevention guidance.^3,12

Through a combination of its national and local health care networks, the VHA has a robust and well-positioned emergency infrastructure to supportcommunity-dwelling older adults during disasters.¹⁴ This network is supported by the VHA Office of Emergency Management, which shares resources and guidance with local emergency managers at each facility as well as individual programs such as the VHA Home Based Primary Care (HBPC) program, which provides 38,000 seriously ill veterans with home medical visits.¹⁵ Working closely with their local and national hospital networks and emergency managers, individual VHA HBPC programs were able to maintain the safety of staff and continuity of care for patients enrolled in HBPC by rapidly administering COVID-19 vaccines to patients, caregivers, and staff, and providing emergency assistance during the 2017 hurricane season.^16,17 These efforts were successful because HBPC practitioners and their patients, had access to a level of emergency-related information, resources, and technology that are often out of reach for individual community-based health care practitioners (HCPs). The US Department of Veterans Affairs (VA) also supports local communities through its Fourth Mission, which provides emergency resources to non-VHA health care facilities (ie, hospitals and nursing homes) during national emergencies and natural disasters.¹⁷ Although there has been an expansion in the definition of shared resources, such as extending behavioral health support to local communities, the VHA has not historically provided these resources to HHAs.¹⁴

This study examines opportunities to leverage VHA emergency management resources to support contracted HHAs and inform other large health system emergency planning efforts. The findings from the exploratory phase are described in this article. We interviewed VHA emergency managers, HBPC and VA staff who coordinate home health care worker services, as well as administrators at contracted HHAs within a Veterans Integrated Services Network (VISN). These findings will inform the second (single-site pilot study) and third (feasibility study) phases. Our intent was to (1) better understand the relationships between VA medical centers (VAMCs) and their contracted HHAs; (2) identify existing VHA emergency protocols to support community-dwelling older adults; and (3) determine opportunities to build on existing infrastructure and relationships to better support contracted HHAs and their staff in emergencies.

Methods

The 18 VISNs act as regional systems of care that are loosely connected to better meet local health needs and maximize access to care. This study was conducted at 6 of 9 VAMCs within VISN 2, the New York/New Jersey VHA Health Care Network.¹⁸ VAMCs that serve urban, rural, and mixed urban/rural catchment areas were included.

Each VAMC has an emergency management program led by an emergency manager, an HBPC program led by a program director and medical director, and a community care or purchased care office that has a liaison who manages contracted home health care worker services. The studyfocused on HBPC programs because they are most likely to interact with veterans’ home health care workers in the home and care for community-dwelling veterans during emergencies. Each VHA also contracts with a series of local HHAs that generally have a dedicated staff member who interfaces with the VHA liaison. Our goal was to interview ≥ 1 emergency manager, ≥ 1 HBPC team member, ≥ 1 community care staff person, and ≥ 1 contracted home health agency administrator at each site to gain multiple perspectives from the range of HCPs serving veterans in the community.

Recruitment and Data Collection

The 6 sites were selected in consultation with VISN 2 leadership for their strong HBPC and emergency management programs. To recruit respondents, we contacted VISN and VAMC leads and used our professional networks to identify a sample of multidisciplinary individuals who represent both community care and HBPC programs who were contacted via email.

Since each VAMC is organized differently, we utilized a snowball sampling approach to identify the appropriate contacts.¹⁹ At the completion of each interview, we asked the participant to suggest additional contacts and introduce us to any remaining stakeholders (eg, the emergency manager) at that site or colleagues at other VISN facilities. Because roles vary among VAMCs, we contacted the person who most closely resembled the identified role and asked them to direct us to a more appropriate contact, if necessary. We asked community care managers to identify 1 to 2 agencies serving the highest volume of patients who are veterans at their site and requested interviews with those liaisons. This resulted in the recruitment of key stakeholders from 4 teams across the 6 sites (Table).

A semistructured interview guide was jointly developed based on constructs of interest, including relationships within VAMCs and between VAMCs and HHAs; existing emergency protocols and experience during disasters; and suggestions and opportunities for supporting agencies during emergencies and potential barriers. Two researchers (TWL and EF) who were trained in qualitative methods jointly conducted interviews using the interview guide, with 1 researcher leading and another taking notes and asking clarifying questions.

Interviews were conducted virtually via Microsoft Teams with respondents at their work locations between September 2022 and January 2023. Interviews were audio recorded and transcribed and 2 authors (TWL and ESO) reviewed transcripts for accuracy. Interviews averaged 47 minutes in length (range, 20-59).

The study was reviewed and determined to be exempt by institutional review boards at the James J. Peters VAMC and Greater Los Angeles VAMC. We asked participants for verbal consent to participate and preserved their confidentiality.

Analysis

Data were analyzed via an inductive approach, which involves drawing salient themes rather than imposing preconceived theories.²⁰ Three researchers (TWL, EF, and ES) listened to and discussed 2 staff interviews and tagged text with specific codes (eg, communication between the VHA and HHA, internal communication, and barriers to case fulfillment) so the team could selectively return to the interview text for deeper analysis, allowing for the development of a final codebook. The project team synthesized the findings to identify higher-level themes, drawing comparisons across and within the respondent groups, including within and between health care systems. Throughout the analysis, we maintained analytic memos, documented discussions, and engaged in analyst triangulation to ensure trustworthiness.^21,22 To ensure the analysis accurately reflected the participants’ understanding, we held 2 virtual member-checking sessions with participants to share preliminary findings and conclusions and solicit feedback. Analysis was conducted using ATLAS.ti version 20.

Results

VHA-based participants described internal emergency management systems that are deployed during a disaster to support patients and staff. Agency participants described their own internal emergency management protocols. Respondents discussed how and when the 2 intersected, as well as opportunities for future mutual support. The analysis identified several themes: (1) relationships between VAMC teams; (2) relationships between VHA and HHAs; (3) VHA and agencies responses during emergencies; (4) receptivity and opportunities for extending VHA resources into the community; and (5) barriers and facilitators to deeper engagement.

Relationships Within VHA (n = 17)

Staff at all VHA sites described close relationships between the internal emergency management and HBPC teams. HBPC teams identified patients who were most at risk during emergencies to triage those with the highest medical needs (eg, patients dependent on home infusion, oxygen, or electronic medical devices) and worked alongside emergency managers to develop plans to continue care during an emergency. HBPC representatives were part of their facilities’ local emergency response committees. Due to this close collaboration, VHA emergency managers were familiar with the needs of homebound veterans and caregivers. “I invite our [HBPC] program manager to attend [committee] meetings and … they’re part of the EOC [emergency operations center]," an emergency manager said. “We work together and I’m constantly in contact with that individual, especially during natural disasters and so forth, to ensure that everybody’s prepared in the community.”

On the other hand, community caremanagers—who described frequent interactions with HBPC teams, largely around coordinating and managing non-VHA home care services—were less likely to have direct relationships with their facility emergency managers. For example, when asked if they had a relationship with their emergency manager, a community care manager admitted, “I [only] know who he is.” They also did not report having structured protocols for veteran outreach during emergencies, “because all those veterans who are receiving [home health care worker] services also belong to a primary care team,” and considered the outreach to be the responsibility of the primary care team and HHA.

Relationships Between the VHA and HHAs (n = 17)

Communication between VAMCs and contracted agencies primarily went through community care managers, who described established long-term relationships with agency administrators. Communication was commonly restricted to operational activities, such as processing referrals and occasional troubleshooting. According to a community care manager most communication is “why haven’t you signed my orders?” There was a general sense from participants that communication was promptly answered, problems were addressed, and professional collegiality existed between the agencies as patients were referred and placed for services. One community care manager reported meeting with agencies regularly, noting, “I talk to them pretty much daily.”

If problems arose, community care managers described themselves as “the liaison” between agencies and VHA HCPs who ordered the referrals. This is particularly the case if the agency needed help finding a VHA clinician or addressing differences in care delivery protocols.

Responding During Emergencies (n = 19)

During emergencies, VHA and agency staff described following their own organization’s protocols and communicating with each other only on a case-by-case basis rather than through formal or systematic channels and had little knowledge of their counterpart’s emergency protocols. Beyond patient care, there was no evidence of information sharing between VHA and agency staff. Regarding sharing information with their local community, an HBPC Program Director said, “it’s almost like the VHA had become siloed” and operated on its own without engaging with community health systems or emergency managers.

Beyond the guidance provided by state departments of public health, HHAs described collaborating with other agencies in their network and relying on their informal professional network to manage the volume of information and updates they followed during emergencies like the COVID-19 pandemic. One agency administrator did not frequently communicate with VHA partners during the pandemic but explained that the local public health department helped work through challenges. However, “we realized pretty quickly they were overloaded and there was only so much they could do.” The agency administrator turned to a “sister agency” and local hospitals, noting, “Wherever you have connections in the field or in the industry, you know you’re going to reach out to people for guidance on policies and… protocol.”

Opportunities for Extending VHA Resources to the Community (n = 16)

All VHA emergency managers were receptive to extending support to community-based HCPS and, in some cases, felt strongly that they were an essential part of veterans’ care networks. Emergency managers offered examples for how they supportedcommunity-based HCPs, such as helping those in the VAMC medical foster home program develop and evaluate emergency plans. Many said they had not explicitly considered HHAs before (Appendix).

Emergency managers also described how supporting community-based HCPs could be considered within the scope of the VHA role and mission, specifically the Fourth Mission. “I think that we should be making our best effort to make sure that we’re also providing that same level [of protection] to the people taking care of the veteran [as our VHA staff],” an emergency manager said. “It’s our responsibility to provide the best for the staff that are going into those homes to take care of that patient.”

In many cases, emergency managers had already developed practical tools that could be easily shared outside the VHA, including weather alerts, trainings, emergency plan templates, and lists of community resources and shelters (Figure 2). A number of these examples built on existing communication channels. One emergency manager said that the extension of resources could be an opportunity to decrease the perceived isolation of home health care workers through regular training for agencies that are providing health care aides, so that they know that “some bigger folks are keeping an eye on it.”

On the agency side, participants noted that some HHAs could benefit more from support than others. While some agencies are well staffed and have good protocols and keep up to date, “There are smaller agencies, agencies that are starting up that may not have the resources to just disseminate all the information. Those are the agencies [that] could well benefit from the VHA,” an HBPC medical director explained. Agency administrators suggested several areas where they would welcome support, including a deeper understanding of available community resources and access to PPE for staff. Regarding informational resources, an administrator said, “Anytime we can get information, it’s good to have it come to you and not always have to go out searching for it.”

Barriers and Facilitators to Partnering With Community Agencies (n = 16)

A primary barrier regarding resource sharing was potential misalignment between each organization’s policies. HHAs followed state and federal public health guidelines, which sometimes differed from VHA policies. Given that agencies care for both VHA and non-VHA clients, questions also arose around how agencies would prioritize information from the VHA, if they were already receiving information from other sources. When asked about information sharing, both VHA staff and agencies agreed staff time to support any additional activities should be weighed against the value of the information gained.

Six participants also shared that education around emergency preparedness could be an opportunity to bridge gaps between VAMCs and their surrounding communities. One local Chief of Community Care noted, “Any opportunity to just give information is going to make it a lot better for the veteran patient … to have something that’s a little more robust.”

Two emergency managers noted the need to be sensitive in the way they engaged with partners, respecting and building on the work that agencies were already doing in this area to ensure VHA was seen as a trusted partner and resource rather than trying to impose new policies or rules on community-based HCPs. “I know that like all leadership in various organizations, there’s a little bit of bristling going on when other people try and tell them what to do,” an HBPC medical director said. “However, if it is established that as a sort of greater level like a state level or a federal level, that VHA can be a resource. I think that as long as that’s recognized by their own professional organizations within each state, then I think that that would be a tremendous advantage to many agencies.”

In terms of sharing physical resources, emergency managers raised concerns around potential liability, although they also acknowledged this issue was important enough to think about potential workarounds. As one emergency manager said, “I want to know that my PPE is not compromised in any way shape or form and that I am in charge of that PPE, so to rely upon going to a home and hoping that [the PPE] wasn’t compromised … would kind of make me a little uneasy.” This emergency manager suggested possible solutions, such as creating a sealed PPE package to give directly to an aide.

Discussion

As the prevalence of climate-related disasters increases, the need to ensure the safety and independence of older adults during emergencies grows more urgent. Health systems must think beyond the direct services they provide and consider the community resources upon which their patients rely. While relationships did not formally exist between VHA emergency managers and community home health HCPs in the sample analyzed in this article, there is precedent and interest in supporting contracted home health agencies caring for veterans in the community. Although not historically part of the VA Fourth Mission, creating a pipeline of support for contracted HHAs by leveraging existing relationships and resources can potentially strengthen its mission to protect older veterans in emergencies, help them age safely in place, and provide a model for health systems to collaborate with community-based HCPs around emergency planning and response (Figure 3).²³

Existing research on the value of health care coalitions highlights the need for established and growing partnerships with a focus on ensuring they are value-added, which echoes concerns we heard in interviews.²⁴ Investment in community partnerships not only includes sharing supplies but also relying on bidirectional support that can be a trusted form of timely information.^1,25 The findings in this study exhibit strong communication practices within the VHA during periods of nonemergency and underscore the untapped value of the pre-existing relationship between VAMCs and their contracted HHAs as an area of potential growth for health care coalitions.

Sharing resources in a way that does not put new demands on partners contributes to the sustainability and value-added nature of coalitions. Examples include establishing new low-investment practices (ie, information sharing) that support capacity and compliance with existing requirements rather than create new responsibilities for either member of the coalition. The relationship between the VHA emergency managers and the VHA HBPC program can act as a guide. The emergency managers interviewed for this study are currently engaged with HBPC programs and therefore understand the needs of homebound older adults and their caregivers. Extending the information already available to the HBPC teams via existing channels strengthens workforce practices and increased security for the shared patient, even without direct relationships between emergency managers and agencies. It is important to understand the limitations of these practices, including concerns around conflicting federal and state mandates, legal concerns around the liability of sharing physical resources (such as PPE), and awareness that the objective is not for the VHA to increase burdens (eg, increasing compliance requirements) but rather to serve as a resource for a mutual population in a shared community.

Offering training and practical resources to HHA home health care workers can help them meet disaster preparedness requirements. This is particularly important considering the growing home care workforce shortages, a topic mentioned by all HBPC and community care participants interviewed for this study.^26,27 Home health care workers report feeling underprepared and isolated while on the job in normal conditions, a sentiment exacerbated by the COVID-19 pandemic.^3,10 Supporting these individuals may help them feel more prepared and connected to their work, improving stability and quality of care.

While these issues are priorities within the VHA, there is growing recognition at the state and federal level of the importance of including older adults and their HCPs in disaster preparedness and response.^5,28 The US Department of Health and Human Services, for example, includes older adults and organizations that serve them on its National Advisory Committee on Seniors and Disasters. The Senate version of the 2023 reauthorization of the Pandemic and All-Hazards Preparedness and Response Act included specific provisions to support community-dwelling older adults and people with disabilities, incorporating funding for community organizations to support continuity of services and avoid institutionalization in an emergency.²⁹ Other proposed legislation includes the Real Emergency Access for Aging and Disability Inclusion for Disasters Act, which would ensure the needs of older adults and people with disabilities are explicitly included in all phases of emergency planning and response.³⁰

The VHA expansion of the its VEText program to include disaster response is an effort to more efficiently extend outreach to older and vulnerable patients who are veterans.³¹ Given these growing efforts, the VHA and other health systems have an opportunity to expand internal emergency preparedness efforts to ensure the health and safety of individuals living in the community.

Limitations

VISN 2 has been a target of terrorism and other disasters. In addition to the sites being initially recruited for their strong emergency management protocols, this context may have biased respondents who are favorable to extending their resources into the community. At the time of recruitment, contracted HHAs were still experiencing staff shortages due to the COVID-19 pandemic, which limited the ability of agency staff to participate in interviews. Additionally, while the comprehensive exploration of VISN 2 facilities allows for confidence of the organizational structures described, the qualitative research design and small study sample, the study findings cannot be immediately generalized to all VISNs.

Conclusions

Many older veterans increasingly rely on home health care workers to age safely. The VHA, as a large national health care system and leader in emergency preparedness, could play an important role in supporting home health care workers and ameliorating their sense of isolation during emergencies and natural disasters. Leveraging existing resources and relationships may be a low-cost, low-effort opportunity to build higher-level interventions that support the needs of patients. Future research and work in this field, including the authors’ ongoing work, will expand agency participation and engage agency staff in conceptualizing pilot projects to ensure they are viable and feasible for the field.

As large-scale natural disasters become more common, health care coalitions and the engagement of health systems with local, state, and federal public health departments have effectively bolstered communities’ resilience via collective sharing and distribution of resources.¹ These resources may include supplies and the dissemination of emergency information, education, and training.² The COVID-19 pandemic demonstrated that larger health care systems including hospital networks and nursing homes are better connected to health care coalition resources than smaller, independent systems, such as community home health agencies.³ This leaves some organizations on their own to meet requirements that maintain continuity of care and support their patients and staff throughout a natural disaster.

Home health care workers play important roles in the care of older adults.⁴ Older adults experience high levels of disability and comorbidities that put them at risk during emergencies; they often require support from paid, family, and neighborhood caregivers to live independently.⁵ More than 9.3 million US adults receive paid care from 2.6 million home health care workers (eg, home health aides and personal care assistants).⁶ Many of these individuals are hired through small independent home health agencies (HHAs), while others may work directly for an individual. When neighborhood resources and family caregiving are disrupted during emergencies, the critical services these workers administer become even more essential to ensuring continued access to medical care and social services.

The importance of these services was underscored by the Centers for Medicare and Medicaid Services 2017 inclusion of HHAs in federal emergency preparedness guidelines.^7,8 The fractured and decentralized nature of the home health care industry means many HHAs struggle to maintain continuous care during emergencies and protect their staff. HHAs, and health care workers in the home, are often isolated, under-resourced, and disconnected from broader emergency planning efforts. Additionally, home care jobs are largely part-time, unstable, and low paying, making the workers themselves vulnerable during emergencies.^3,9-13

This is a significant issue for the Veterans Health Administration (VHA), which annually purchases 10.5 million home health care worker visits for 150,000 veterans from community-based HHAs to enable those individuals to live independently. Figure 1 illustrates the existing structure of directly provided and contracted VHA services for community-dwelling veterans, highlighting the circle of care around the veteran.^8,9 Home health care workers anchored health care teams during the COVID-19 pandemic, observing and reporting on patients’ well-being to family caregivers, primary care practitioners, and HHAs. They also provided critical emotional support and companionship to patients isolated from family and friends.⁹ These workers also exposed themselves and their families to considerable risk and often lacked the protection afforded by personal protective equipment (PPE) in accordance with infection prevention guidance.^3,12

Through a combination of its national and local health care networks, the VHA has a robust and well-positioned emergency infrastructure to supportcommunity-dwelling older adults during disasters.¹⁴ This network is supported by the VHA Office of Emergency Management, which shares resources and guidance with local emergency managers at each facility as well as individual programs such as the VHA Home Based Primary Care (HBPC) program, which provides 38,000 seriously ill veterans with home medical visits.¹⁵ Working closely with their local and national hospital networks and emergency managers, individual VHA HBPC programs were able to maintain the safety of staff and continuity of care for patients enrolled in HBPC by rapidly administering COVID-19 vaccines to patients, caregivers, and staff, and providing emergency assistance during the 2017 hurricane season.^16,17 These efforts were successful because HBPC practitioners and their patients, had access to a level of emergency-related information, resources, and technology that are often out of reach for individual community-based health care practitioners (HCPs). The US Department of Veterans Affairs (VA) also supports local communities through its Fourth Mission, which provides emergency resources to non-VHA health care facilities (ie, hospitals and nursing homes) during national emergencies and natural disasters.¹⁷ Although there has been an expansion in the definition of shared resources, such as extending behavioral health support to local communities, the VHA has not historically provided these resources to HHAs.¹⁴

This study examines opportunities to leverage VHA emergency management resources to support contracted HHAs and inform other large health system emergency planning efforts. The findings from the exploratory phase are described in this article. We interviewed VHA emergency managers, HBPC and VA staff who coordinate home health care worker services, as well as administrators at contracted HHAs within a Veterans Integrated Services Network (VISN). These findings will inform the second (single-site pilot study) and third (feasibility study) phases. Our intent was to (1) better understand the relationships between VA medical centers (VAMCs) and their contracted HHAs; (2) identify existing VHA emergency protocols to support community-dwelling older adults; and (3) determine opportunities to build on existing infrastructure and relationships to better support contracted HHAs and their staff in emergencies.

Methods

The 18 VISNs act as regional systems of care that are loosely connected to better meet local health needs and maximize access to care. This study was conducted at 6 of 9 VAMCs within VISN 2, the New York/New Jersey VHA Health Care Network.¹⁸ VAMCs that serve urban, rural, and mixed urban/rural catchment areas were included.

Each VAMC has an emergency management program led by an emergency manager, an HBPC program led by a program director and medical director, and a community care or purchased care office that has a liaison who manages contracted home health care worker services. The studyfocused on HBPC programs because they are most likely to interact with veterans’ home health care workers in the home and care for community-dwelling veterans during emergencies. Each VHA also contracts with a series of local HHAs that generally have a dedicated staff member who interfaces with the VHA liaison. Our goal was to interview ≥ 1 emergency manager, ≥ 1 HBPC team member, ≥ 1 community care staff person, and ≥ 1 contracted home health agency administrator at each site to gain multiple perspectives from the range of HCPs serving veterans in the community.

Recruitment and Data Collection

The 6 sites were selected in consultation with VISN 2 leadership for their strong HBPC and emergency management programs. To recruit respondents, we contacted VISN and VAMC leads and used our professional networks to identify a sample of multidisciplinary individuals who represent both community care and HBPC programs who were contacted via email.

Since each VAMC is organized differently, we utilized a snowball sampling approach to identify the appropriate contacts.¹⁹ At the completion of each interview, we asked the participant to suggest additional contacts and introduce us to any remaining stakeholders (eg, the emergency manager) at that site or colleagues at other VISN facilities. Because roles vary among VAMCs, we contacted the person who most closely resembled the identified role and asked them to direct us to a more appropriate contact, if necessary. We asked community care managers to identify 1 to 2 agencies serving the highest volume of patients who are veterans at their site and requested interviews with those liaisons. This resulted in the recruitment of key stakeholders from 4 teams across the 6 sites (Table).

A semistructured interview guide was jointly developed based on constructs of interest, including relationships within VAMCs and between VAMCs and HHAs; existing emergency protocols and experience during disasters; and suggestions and opportunities for supporting agencies during emergencies and potential barriers. Two researchers (TWL and EF) who were trained in qualitative methods jointly conducted interviews using the interview guide, with 1 researcher leading and another taking notes and asking clarifying questions.

Interviews were conducted virtually via Microsoft Teams with respondents at their work locations between September 2022 and January 2023. Interviews were audio recorded and transcribed and 2 authors (TWL and ESO) reviewed transcripts for accuracy. Interviews averaged 47 minutes in length (range, 20-59).

The study was reviewed and determined to be exempt by institutional review boards at the James J. Peters VAMC and Greater Los Angeles VAMC. We asked participants for verbal consent to participate and preserved their confidentiality.

Analysis

Data were analyzed via an inductive approach, which involves drawing salient themes rather than imposing preconceived theories.²⁰ Three researchers (TWL, EF, and ES) listened to and discussed 2 staff interviews and tagged text with specific codes (eg, communication between the VHA and HHA, internal communication, and barriers to case fulfillment) so the team could selectively return to the interview text for deeper analysis, allowing for the development of a final codebook. The project team synthesized the findings to identify higher-level themes, drawing comparisons across and within the respondent groups, including within and between health care systems. Throughout the analysis, we maintained analytic memos, documented discussions, and engaged in analyst triangulation to ensure trustworthiness.^21,22 To ensure the analysis accurately reflected the participants’ understanding, we held 2 virtual member-checking sessions with participants to share preliminary findings and conclusions and solicit feedback. Analysis was conducted using ATLAS.ti version 20.

Results

VHA-based participants described internal emergency management systems that are deployed during a disaster to support patients and staff. Agency participants described their own internal emergency management protocols. Respondents discussed how and when the 2 intersected, as well as opportunities for future mutual support. The analysis identified several themes: (1) relationships between VAMC teams; (2) relationships between VHA and HHAs; (3) VHA and agencies responses during emergencies; (4) receptivity and opportunities for extending VHA resources into the community; and (5) barriers and facilitators to deeper engagement.

Relationships Within VHA (n = 17)

Staff at all VHA sites described close relationships between the internal emergency management and HBPC teams. HBPC teams identified patients who were most at risk during emergencies to triage those with the highest medical needs (eg, patients dependent on home infusion, oxygen, or electronic medical devices) and worked alongside emergency managers to develop plans to continue care during an emergency. HBPC representatives were part of their facilities’ local emergency response committees. Due to this close collaboration, VHA emergency managers were familiar with the needs of homebound veterans and caregivers. “I invite our [HBPC] program manager to attend [committee] meetings and … they’re part of the EOC [emergency operations center]," an emergency manager said. “We work together and I’m constantly in contact with that individual, especially during natural disasters and so forth, to ensure that everybody’s prepared in the community.”

On the other hand, community caremanagers—who described frequent interactions with HBPC teams, largely around coordinating and managing non-VHA home care services—were less likely to have direct relationships with their facility emergency managers. For example, when asked if they had a relationship with their emergency manager, a community care manager admitted, “I [only] know who he is.” They also did not report having structured protocols for veteran outreach during emergencies, “because all those veterans who are receiving [home health care worker] services also belong to a primary care team,” and considered the outreach to be the responsibility of the primary care team and HHA.

Relationships Between the VHA and HHAs (n = 17)

Communication between VAMCs and contracted agencies primarily went through community care managers, who described established long-term relationships with agency administrators. Communication was commonly restricted to operational activities, such as processing referrals and occasional troubleshooting. According to a community care manager most communication is “why haven’t you signed my orders?” There was a general sense from participants that communication was promptly answered, problems were addressed, and professional collegiality existed between the agencies as patients were referred and placed for services. One community care manager reported meeting with agencies regularly, noting, “I talk to them pretty much daily.”

If problems arose, community care managers described themselves as “the liaison” between agencies and VHA HCPs who ordered the referrals. This is particularly the case if the agency needed help finding a VHA clinician or addressing differences in care delivery protocols.

Responding During Emergencies (n = 19)

During emergencies, VHA and agency staff described following their own organization’s protocols and communicating with each other only on a case-by-case basis rather than through formal or systematic channels and had little knowledge of their counterpart’s emergency protocols. Beyond patient care, there was no evidence of information sharing between VHA and agency staff. Regarding sharing information with their local community, an HBPC Program Director said, “it’s almost like the VHA had become siloed” and operated on its own without engaging with community health systems or emergency managers.

Beyond the guidance provided by state departments of public health, HHAs described collaborating with other agencies in their network and relying on their informal professional network to manage the volume of information and updates they followed during emergencies like the COVID-19 pandemic. One agency administrator did not frequently communicate with VHA partners during the pandemic but explained that the local public health department helped work through challenges. However, “we realized pretty quickly they were overloaded and there was only so much they could do.” The agency administrator turned to a “sister agency” and local hospitals, noting, “Wherever you have connections in the field or in the industry, you know you’re going to reach out to people for guidance on policies and… protocol.”

Opportunities for Extending VHA Resources to the Community (n = 16)

All VHA emergency managers were receptive to extending support to community-based HCPS and, in some cases, felt strongly that they were an essential part of veterans’ care networks. Emergency managers offered examples for how they supportedcommunity-based HCPs, such as helping those in the VAMC medical foster home program develop and evaluate emergency plans. Many said they had not explicitly considered HHAs before (Appendix).

Emergency managers also described how supporting community-based HCPs could be considered within the scope of the VHA role and mission, specifically the Fourth Mission. “I think that we should be making our best effort to make sure that we’re also providing that same level [of protection] to the people taking care of the veteran [as our VHA staff],” an emergency manager said. “It’s our responsibility to provide the best for the staff that are going into those homes to take care of that patient.”

In many cases, emergency managers had already developed practical tools that could be easily shared outside the VHA, including weather alerts, trainings, emergency plan templates, and lists of community resources and shelters (Figure 2). A number of these examples built on existing communication channels. One emergency manager said that the extension of resources could be an opportunity to decrease the perceived isolation of home health care workers through regular training for agencies that are providing health care aides, so that they know that “some bigger folks are keeping an eye on it.”

On the agency side, participants noted that some HHAs could benefit more from support than others. While some agencies are well staffed and have good protocols and keep up to date, “There are smaller agencies, agencies that are starting up that may not have the resources to just disseminate all the information. Those are the agencies [that] could well benefit from the VHA,” an HBPC medical director explained. Agency administrators suggested several areas where they would welcome support, including a deeper understanding of available community resources and access to PPE for staff. Regarding informational resources, an administrator said, “Anytime we can get information, it’s good to have it come to you and not always have to go out searching for it.”

Barriers and Facilitators to Partnering With Community Agencies (n = 16)

A primary barrier regarding resource sharing was potential misalignment between each organization’s policies. HHAs followed state and federal public health guidelines, which sometimes differed from VHA policies. Given that agencies care for both VHA and non-VHA clients, questions also arose around how agencies would prioritize information from the VHA, if they were already receiving information from other sources. When asked about information sharing, both VHA staff and agencies agreed staff time to support any additional activities should be weighed against the value of the information gained.

Six participants also shared that education around emergency preparedness could be an opportunity to bridge gaps between VAMCs and their surrounding communities. One local Chief of Community Care noted, “Any opportunity to just give information is going to make it a lot better for the veteran patient … to have something that’s a little more robust.”

Two emergency managers noted the need to be sensitive in the way they engaged with partners, respecting and building on the work that agencies were already doing in this area to ensure VHA was seen as a trusted partner and resource rather than trying to impose new policies or rules on community-based HCPs. “I know that like all leadership in various organizations, there’s a little bit of bristling going on when other people try and tell them what to do,” an HBPC medical director said. “However, if it is established that as a sort of greater level like a state level or a federal level, that VHA can be a resource. I think that as long as that’s recognized by their own professional organizations within each state, then I think that that would be a tremendous advantage to many agencies.”

In terms of sharing physical resources, emergency managers raised concerns around potential liability, although they also acknowledged this issue was important enough to think about potential workarounds. As one emergency manager said, “I want to know that my PPE is not compromised in any way shape or form and that I am in charge of that PPE, so to rely upon going to a home and hoping that [the PPE] wasn’t compromised … would kind of make me a little uneasy.” This emergency manager suggested possible solutions, such as creating a sealed PPE package to give directly to an aide.

Discussion

As the prevalence of climate-related disasters increases, the need to ensure the safety and independence of older adults during emergencies grows more urgent. Health systems must think beyond the direct services they provide and consider the community resources upon which their patients rely. While relationships did not formally exist between VHA emergency managers and community home health HCPs in the sample analyzed in this article, there is precedent and interest in supporting contracted home health agencies caring for veterans in the community. Although not historically part of the VA Fourth Mission, creating a pipeline of support for contracted HHAs by leveraging existing relationships and resources can potentially strengthen its mission to protect older veterans in emergencies, help them age safely in place, and provide a model for health systems to collaborate with community-based HCPs around emergency planning and response (Figure 3).²³

Existing research on the value of health care coalitions highlights the need for established and growing partnerships with a focus on ensuring they are value-added, which echoes concerns we heard in interviews.²⁴ Investment in community partnerships not only includes sharing supplies but also relying on bidirectional support that can be a trusted form of timely information.^1,25 The findings in this study exhibit strong communication practices within the VHA during periods of nonemergency and underscore the untapped value of the pre-existing relationship between VAMCs and their contracted HHAs as an area of potential growth for health care coalitions.

Sharing resources in a way that does not put new demands on partners contributes to the sustainability and value-added nature of coalitions. Examples include establishing new low-investment practices (ie, information sharing) that support capacity and compliance with existing requirements rather than create new responsibilities for either member of the coalition. The relationship between the VHA emergency managers and the VHA HBPC program can act as a guide. The emergency managers interviewed for this study are currently engaged with HBPC programs and therefore understand the needs of homebound older adults and their caregivers. Extending the information already available to the HBPC teams via existing channels strengthens workforce practices and increased security for the shared patient, even without direct relationships between emergency managers and agencies. It is important to understand the limitations of these practices, including concerns around conflicting federal and state mandates, legal concerns around the liability of sharing physical resources (such as PPE), and awareness that the objective is not for the VHA to increase burdens (eg, increasing compliance requirements) but rather to serve as a resource for a mutual population in a shared community.

Offering training and practical resources to HHA home health care workers can help them meet disaster preparedness requirements. This is particularly important considering the growing home care workforce shortages, a topic mentioned by all HBPC and community care participants interviewed for this study.^26,27 Home health care workers report feeling underprepared and isolated while on the job in normal conditions, a sentiment exacerbated by the COVID-19 pandemic.^3,10 Supporting these individuals may help them feel more prepared and connected to their work, improving stability and quality of care.

While these issues are priorities within the VHA, there is growing recognition at the state and federal level of the importance of including older adults and their HCPs in disaster preparedness and response.^5,28 The US Department of Health and Human Services, for example, includes older adults and organizations that serve them on its National Advisory Committee on Seniors and Disasters. The Senate version of the 2023 reauthorization of the Pandemic and All-Hazards Preparedness and Response Act included specific provisions to support community-dwelling older adults and people with disabilities, incorporating funding for community organizations to support continuity of services and avoid institutionalization in an emergency.²⁹ Other proposed legislation includes the Real Emergency Access for Aging and Disability Inclusion for Disasters Act, which would ensure the needs of older adults and people with disabilities are explicitly included in all phases of emergency planning and response.³⁰

The VHA expansion of the its VEText program to include disaster response is an effort to more efficiently extend outreach to older and vulnerable patients who are veterans.³¹ Given these growing efforts, the VHA and other health systems have an opportunity to expand internal emergency preparedness efforts to ensure the health and safety of individuals living in the community.

Limitations

VISN 2 has been a target of terrorism and other disasters. In addition to the sites being initially recruited for their strong emergency management protocols, this context may have biased respondents who are favorable to extending their resources into the community. At the time of recruitment, contracted HHAs were still experiencing staff shortages due to the COVID-19 pandemic, which limited the ability of agency staff to participate in interviews. Additionally, while the comprehensive exploration of VISN 2 facilities allows for confidence of the organizational structures described, the qualitative research design and small study sample, the study findings cannot be immediately generalized to all VISNs.

Conclusions

Many older veterans increasingly rely on home health care workers to age safely. The VHA, as a large national health care system and leader in emergency preparedness, could play an important role in supporting home health care workers and ameliorating their sense of isolation during emergencies and natural disasters. Leveraging existing resources and relationships may be a low-cost, low-effort opportunity to build higher-level interventions that support the needs of patients. Future research and work in this field, including the authors’ ongoing work, will expand agency participation and engage agency staff in conceptualizing pilot projects to ensure they are viable and feasible for the field.