The Journal of Family Practice

The presence and location of this mass, paired with the patient’s symptoms, led to the diagnosis of pelvic inflammatory disease (PID).

PID is an acute infection of the upper genital tract in women that is thought to be due to an ascending infection from the lower genital tract. Diagnosis of PID in middle-aged women is a challenge, given the broad differential diagnosis of nonspecific presenting symptoms, lower index of suspicion in this age group, and unknown exact incidence of PID in postmenopausal women. Delay in diagnosis in postmenopausal women can pose serious potential complications such as tubo-ovarian abscess (TOA)—as was seen with this patient—and concurrent gynecologic malignancy found on pathology of TOA specimens.

Risk factors for PID in the postmenopausal population include recent uterine instrumentation, history of prior PID, and structural abnormalities such as cervical stenosis, uterine anatomic abnormalities, or tubal disease.

The Centers for Disease Control and Prevention (CDC) 2015 Sexually Transmitted Diseases Treatment Guidelines recommend presumptive treatment for PID in women with pelvic or lower abdominal pain with 1 or more of the following clinical criteria: cervical motion tenderness, uterine tenderness, or adnexal tenderness. The CDC also suggests that the most specific criteria for PID include endometrial biopsy consistent with endometritis, imaging (transvaginal ultrasound or magnetic resonance imaging) demonstrating fluid-filled tubes, or laparoscopic findings consistent with PID.

Due to the polymicrobial nature of PID, antibiotics should cover not only gonorrhea and chlamydia but also anaerobic pathogens. CDC guidelines recommend the following treatment:

• intravenous (IV) cefotetan (2 g bid) plus doxycycline (100 mg PO or IV bid),
• IV cefoxitin (2 g qid) plus doxycycline (100 mg PO or IV bid), or
• IV clindamycin (900 mg tid) plus IV or intramuscular gentamicin loading dose (2 mg/kg) followed by a maintenance dose (1.5 mg/kg tid).

Due to the increased risk of malignancy in postmenopausal women with TOA, surgical intervention may be needed.

This patient underwent diagnostic laparoscopy, hysterectomy, left salpingo-oophorectomy, and right salpingectomy (with her right ovary left in place due to her perimenopausal status). Intraoperatively, she was found to have cervical stenosis. Postoperatively, she improved on IV cefoxitin (2 g qid) and IV doxycycline (100 mg bid), which was eventually transitioned to oral doxycycline (100 mg bid) and metronidazole (500 mg bid) on discharge. She made a full recovery and is doing well.

‌

This case was adapted from: Khoo CP. Fever, abdominal pain, and adnexal mass. J Fam Pract. 2020;69:101-103

The presence and location of this mass, paired with the patient’s symptoms, led to the diagnosis of pelvic inflammatory disease (PID).

PID is an acute infection of the upper genital tract in women that is thought to be due to an ascending infection from the lower genital tract. Diagnosis of PID in middle-aged women is a challenge, given the broad differential diagnosis of nonspecific presenting symptoms, lower index of suspicion in this age group, and unknown exact incidence of PID in postmenopausal women. Delay in diagnosis in postmenopausal women can pose serious potential complications such as tubo-ovarian abscess (TOA)—as was seen with this patient—and concurrent gynecologic malignancy found on pathology of TOA specimens.

Risk factors for PID in the postmenopausal population include recent uterine instrumentation, history of prior PID, and structural abnormalities such as cervical stenosis, uterine anatomic abnormalities, or tubal disease.

The Centers for Disease Control and Prevention (CDC) 2015 Sexually Transmitted Diseases Treatment Guidelines recommend presumptive treatment for PID in women with pelvic or lower abdominal pain with 1 or more of the following clinical criteria: cervical motion tenderness, uterine tenderness, or adnexal tenderness. The CDC also suggests that the most specific criteria for PID include endometrial biopsy consistent with endometritis, imaging (transvaginal ultrasound or magnetic resonance imaging) demonstrating fluid-filled tubes, or laparoscopic findings consistent with PID.

Due to the polymicrobial nature of PID, antibiotics should cover not only gonorrhea and chlamydia but also anaerobic pathogens. CDC guidelines recommend the following treatment:

• intravenous (IV) cefotetan (2 g bid) plus doxycycline (100 mg PO or IV bid),
• IV cefoxitin (2 g qid) plus doxycycline (100 mg PO or IV bid), or
• IV clindamycin (900 mg tid) plus IV or intramuscular gentamicin loading dose (2 mg/kg) followed by a maintenance dose (1.5 mg/kg tid).

Due to the increased risk of malignancy in postmenopausal women with TOA, surgical intervention may be needed.

This patient underwent diagnostic laparoscopy, hysterectomy, left salpingo-oophorectomy, and right salpingectomy (with her right ovary left in place due to her perimenopausal status). Intraoperatively, she was found to have cervical stenosis. Postoperatively, she improved on IV cefoxitin (2 g qid) and IV doxycycline (100 mg bid), which was eventually transitioned to oral doxycycline (100 mg bid) and metronidazole (500 mg bid) on discharge. She made a full recovery and is doing well.

‌

This case was adapted from: Khoo CP. Fever, abdominal pain, and adnexal mass. J Fam Pract. 2020;69:101-103

The presence and location of this mass, paired with the patient’s symptoms, led to the diagnosis of pelvic inflammatory disease (PID).

PID is an acute infection of the upper genital tract in women that is thought to be due to an ascending infection from the lower genital tract. Diagnosis of PID in middle-aged women is a challenge, given the broad differential diagnosis of nonspecific presenting symptoms, lower index of suspicion in this age group, and unknown exact incidence of PID in postmenopausal women. Delay in diagnosis in postmenopausal women can pose serious potential complications such as tubo-ovarian abscess (TOA)—as was seen with this patient—and concurrent gynecologic malignancy found on pathology of TOA specimens.

Risk factors for PID in the postmenopausal population include recent uterine instrumentation, history of prior PID, and structural abnormalities such as cervical stenosis, uterine anatomic abnormalities, or tubal disease.

The Centers for Disease Control and Prevention (CDC) 2015 Sexually Transmitted Diseases Treatment Guidelines recommend presumptive treatment for PID in women with pelvic or lower abdominal pain with 1 or more of the following clinical criteria: cervical motion tenderness, uterine tenderness, or adnexal tenderness. The CDC also suggests that the most specific criteria for PID include endometrial biopsy consistent with endometritis, imaging (transvaginal ultrasound or magnetic resonance imaging) demonstrating fluid-filled tubes, or laparoscopic findings consistent with PID.

Due to the polymicrobial nature of PID, antibiotics should cover not only gonorrhea and chlamydia but also anaerobic pathogens. CDC guidelines recommend the following treatment:

• intravenous (IV) cefotetan (2 g bid) plus doxycycline (100 mg PO or IV bid),
• IV cefoxitin (2 g qid) plus doxycycline (100 mg PO or IV bid), or
• IV clindamycin (900 mg tid) plus IV or intramuscular gentamicin loading dose (2 mg/kg) followed by a maintenance dose (1.5 mg/kg tid).

Due to the increased risk of malignancy in postmenopausal women with TOA, surgical intervention may be needed.

This patient underwent diagnostic laparoscopy, hysterectomy, left salpingo-oophorectomy, and right salpingectomy (with her right ovary left in place due to her perimenopausal status). Intraoperatively, she was found to have cervical stenosis. Postoperatively, she improved on IV cefoxitin (2 g qid) and IV doxycycline (100 mg bid), which was eventually transitioned to oral doxycycline (100 mg bid) and metronidazole (500 mg bid) on discharge. She made a full recovery and is doing well.

‌

This case was adapted from: Khoo CP. Fever, abdominal pain, and adnexal mass. J Fam Pract. 2020;69:101-103

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

REFERENCES

1. American Academy of Family Physicians. Lung cancer: lung cancer screening in adults. AAFP Clinical Preventive Service Recommendations. Accessed April 26, 2021. www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/lung-cancer.html
2. USPSTF. Screening for lung cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:962-970. doi:10.1001/jama.2021.1117
3. Jonas DE, Reuland DS, Reddy, SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;325:971-987. doi:10.1001/jama.2021.0377
4. Henderson LM, Rivera MP, Basch E. Broadened eligibility for lung cancer screening: challenges and uncertainty for implementation and equity. JAMA. 2021;325:939-941. doi:10.1001/jama.2020.26422
5. Meza R, Jeon J, Toumazis I, et al. Evaluation of the benefits and harms of lung cancer screening with low-dose computed tomography: modeling study for the US Preventive Services Task Force. JAMA. 2021;325:988-997. doi:10.1001/jama.2021.1077

Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.

It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.¹ The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.

Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.

In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.

It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.¹ The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.

Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.

In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Fortunately, the dermoscopy images of these 2 small palmar lesions showed a pattern of pigmentation that aligned in the furrows and was consistent with benign palmar nevi.

It is not uncommon to have nevi on the palms or soles of the feet, so it is important to distinguish between acral lentiginous melanoma (ALM) and benign nevi. ALM is the least common form of melanoma. In contrast to other types of melanoma, it is not considered secondary to excessive sun exposure. Clinically, ALM presents with irregular, enlarging pigmentation that follows, or crosses, the raised ridges of the palms or soles.¹ The pigmented areas can progress to ulcerated or bleeding lesions. As with other melanomas, early diagnosis and removal is important to optimize prognosis.

Removal of lesions suspicious for ALM can be achieved in several ways: deep shave biopsy, punch excision if the lesion is small, excision with narrow margins, or, if the lesion is large, by a selective punch biopsy of the most suspicious portion of the lesion (typically the thickest and most irregular area). Larger diameter lesions that are raised and irregular are more worrisome than this patient’s 2-mm macular lesions.

In this case, the patient was reassured that the lesions did not require excision. She was advised to continue to monitor her lesions for growth or changes over time and to return for evaluation, as needed. She was also counseled regarding the American Cancer Society’s ABCDE rules (Asymmetry, Border irregularity, Color, Diameter, Elevation or Evolving) regarding melanomas.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

A punch biopsy revealed that the patient had granuloma annulare (GA).

GA is usually a self-limiting disorder that manifests as a single or, less commonly, multiple nonscaly, red, annular lesions that are typically found on the extremities. It frequently starts as a papule or cluster of papules before coalescing into its classic annular pattern. Biopsy is not usually needed to make the diagnosis when annular lesions are present. In this case, the lesions displayed the Koebner phenomenon, occurring along her areolar scar, making diagnosis more difficult and necessitating the biopsy. While the cause of GA is unknown, it has been found more often in women than men, but has no predilection for race, ethnicity, or geographic areas.¹

GA is typically asymptomatic and can resolve spontaneously. Treatment is often performed for cosmetic reasons. First-line therapies include topical corticosteroids, topical tacrolimus, imiquimod cream, intralesional injections into the elevated border with 2.5 to 5 mg/mL triamcinolone acetonide, or destructive methods such as cryosurgery or pulsed dye laser therapy.¹

After a discussion of treatment options, this patient chose watchful waiting.

‌

Image courtesy of Kamini Geer, MD, and text courtesy of Kamini Geer, MD, AdventHealth East Orlando Osteopathic Family Medicine Residency and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A punch biopsy revealed that the patient had granuloma annulare (GA).

GA is usually a self-limiting disorder that manifests as a single or, less commonly, multiple nonscaly, red, annular lesions that are typically found on the extremities. It frequently starts as a papule or cluster of papules before coalescing into its classic annular pattern. Biopsy is not usually needed to make the diagnosis when annular lesions are present. In this case, the lesions displayed the Koebner phenomenon, occurring along her areolar scar, making diagnosis more difficult and necessitating the biopsy. While the cause of GA is unknown, it has been found more often in women than men, but has no predilection for race, ethnicity, or geographic areas.¹

GA is typically asymptomatic and can resolve spontaneously. Treatment is often performed for cosmetic reasons. First-line therapies include topical corticosteroids, topical tacrolimus, imiquimod cream, intralesional injections into the elevated border with 2.5 to 5 mg/mL triamcinolone acetonide, or destructive methods such as cryosurgery or pulsed dye laser therapy.¹

After a discussion of treatment options, this patient chose watchful waiting.

‌

Image courtesy of Kamini Geer, MD, and text courtesy of Kamini Geer, MD, AdventHealth East Orlando Osteopathic Family Medicine Residency and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

A punch biopsy revealed that the patient had granuloma annulare (GA).

GA is usually a self-limiting disorder that manifests as a single or, less commonly, multiple nonscaly, red, annular lesions that are typically found on the extremities. It frequently starts as a papule or cluster of papules before coalescing into its classic annular pattern. Biopsy is not usually needed to make the diagnosis when annular lesions are present. In this case, the lesions displayed the Koebner phenomenon, occurring along her areolar scar, making diagnosis more difficult and necessitating the biopsy. While the cause of GA is unknown, it has been found more often in women than men, but has no predilection for race, ethnicity, or geographic areas.¹

GA is typically asymptomatic and can resolve spontaneously. Treatment is often performed for cosmetic reasons. First-line therapies include topical corticosteroids, topical tacrolimus, imiquimod cream, intralesional injections into the elevated border with 2.5 to 5 mg/mL triamcinolone acetonide, or destructive methods such as cryosurgery or pulsed dye laser therapy.¹

After a discussion of treatment options, this patient chose watchful waiting.

‌

Image courtesy of Kamini Geer, MD, and text courtesy of Kamini Geer, MD, AdventHealth East Orlando Osteopathic Family Medicine Residency and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Dr. Crain’s excellent review, “Breaking the cycle of medication overuse headache” (J Fam Pract. 2021;70:20-28) provides an approach to the diagnosis and treatment of this common disorder that is consistent with most expert opinion and published guidelines. However, like most articles on this subject, it is missing a critical review of the evidence that supports the existence of this condition and the recommended treatments. 

The strong association between intractable headaches and quantity of medication used makes the diagnosis of medication overuse headache (MOH) attractive with plausible (if unproven) pathophysiological mechanisms. However, reversing the direction of causation (intractable headaches lead to more medication) seems just as likely. While MOH is taken as an article of faith by most headache experts, high-quality studies in support of this theory have not yet been performed.¹

On the other hand, fear of MOH often leads to rigid, arbitrary limitations of abortive medications, blaming of the patient for their symptoms, and the substitution of a host of pharmacologic and nonpharmacologic interventions that similarly lack evidence of efficacy. Patients with chronic migraine are told to take abortive medications early in the headache but not to take them more than twice per week. They hoard their medications while trying to decide if each daily headache is the “big one” that merits depleting their limited supply of medication.

Avoiding medication “overuse” and prescribing from our growing armamentarium of effective preventive medications remain important strategies. However, until we have better evidence, we need to be a little more flexible in prescribing abortive medications and avoid accepting the MOH paradigm as gospel.

David A. Silverstein, MD
Buffalo, NY

Dr. Crain’s excellent review, “Breaking the cycle of medication overuse headache” (J Fam Pract. 2021;70:20-28) provides an approach to the diagnosis and treatment of this common disorder that is consistent with most expert opinion and published guidelines. However, like most articles on this subject, it is missing a critical review of the evidence that supports the existence of this condition and the recommended treatments. 

The strong association between intractable headaches and quantity of medication used makes the diagnosis of medication overuse headache (MOH) attractive with plausible (if unproven) pathophysiological mechanisms. However, reversing the direction of causation (intractable headaches lead to more medication) seems just as likely. While MOH is taken as an article of faith by most headache experts, high-quality studies in support of this theory have not yet been performed.¹

On the other hand, fear of MOH often leads to rigid, arbitrary limitations of abortive medications, blaming of the patient for their symptoms, and the substitution of a host of pharmacologic and nonpharmacologic interventions that similarly lack evidence of efficacy. Patients with chronic migraine are told to take abortive medications early in the headache but not to take them more than twice per week. They hoard their medications while trying to decide if each daily headache is the “big one” that merits depleting their limited supply of medication.

Avoiding medication “overuse” and prescribing from our growing armamentarium of effective preventive medications remain important strategies. However, until we have better evidence, we need to be a little more flexible in prescribing abortive medications and avoid accepting the MOH paradigm as gospel.

David A. Silverstein, MD
Buffalo, NY

Dr. Crain’s excellent review, “Breaking the cycle of medication overuse headache” (J Fam Pract. 2021;70:20-28) provides an approach to the diagnosis and treatment of this common disorder that is consistent with most expert opinion and published guidelines. However, like most articles on this subject, it is missing a critical review of the evidence that supports the existence of this condition and the recommended treatments. 

The strong association between intractable headaches and quantity of medication used makes the diagnosis of medication overuse headache (MOH) attractive with plausible (if unproven) pathophysiological mechanisms. However, reversing the direction of causation (intractable headaches lead to more medication) seems just as likely. While MOH is taken as an article of faith by most headache experts, high-quality studies in support of this theory have not yet been performed.¹

On the other hand, fear of MOH often leads to rigid, arbitrary limitations of abortive medications, blaming of the patient for their symptoms, and the substitution of a host of pharmacologic and nonpharmacologic interventions that similarly lack evidence of efficacy. Patients with chronic migraine are told to take abortive medications early in the headache but not to take them more than twice per week. They hoard their medications while trying to decide if each daily headache is the “big one” that merits depleting their limited supply of medication.

Avoiding medication “overuse” and prescribing from our growing armamentarium of effective preventive medications remain important strategies. However, until we have better evidence, we need to be a little more flexible in prescribing abortive medications and avoid accepting the MOH paradigm as gospel.

David A. Silverstein, MD
Buffalo, NY

Mnemonics are often used to help remember complex groups of individual items related to a common theme. Studies have shown that college students studying with mnemonics outperform students using rote learning, suggesting that mnemonics are useful in retention of facts. ¹

In 1 study, researchers compared memory athletes and control subjects before and after mnemonic training. ² Findings showed that mnemonics created connectivity changes in the control group similar to memory athletes at baseline. These changes persisted for as long as 4 months after training, demonstrating that mnemonics have long-lasting effects on memory capacity. ²  

The most frequently used forms of medical mnemonics are acronyms or acrostics. Acronyms are words in which each letter in the word corresponds to a series of words to be remembered. ³ A familiar example of a medical acronym is “SLUDGE,” which represents the symptoms for cholinergic toxicity (salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis). An acrostic involves a phrase in which the first letter of each word corresponds to the first letter of a word to be remembered. ³ A commonly used acrostic phrase for the memorization of the 12 cranial nerves is “On Old Olympus’ Towering Tops A Finn And German Viewed Some Hops”: olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, auditory (vestibulocochlear), glossopharyngeal, vagus, spinal accessory, hypoglossal.

Mnemonics are an effective way for medical students, residents, and current practitioners to effortlessly recall information. For example, COVERABCD is an acronym that stands for circulation/capnograph/color, oxygen, ventilation, endotracheal tube, review of equipment, airway, breathing, circulation, and drugs. ⁴ Runciman et al showed that the use of the acronym COVERABCD could have prevented or mitigated 60% of 2000 anesthetic incidents. ⁴ Another mnemonic, FAST, used to assess for a stroke, reduced median hospital arrival times by more than an hour. ⁵    

There are hundreds of mnemonics related to medical practice. Collections of those that might be useful for family practitioners and medical residents can be found at the following links: 

https://epomedicine.com/medical-mnemonics/  

www.oxfordmedicaleducation.com/medical-mnemonics/  

Kristyn McKnight, PharmD candidate
Hannah Lutz, PharmD candidate
Tracy Mahvan, MBA, PharmD, BCGP
School of Pharmacy, University of Wyoming, Laramie

Mnemonics are often used to help remember complex groups of individual items related to a common theme. Studies have shown that college students studying with mnemonics outperform students using rote learning, suggesting that mnemonics are useful in retention of facts. ¹

In 1 study, researchers compared memory athletes and control subjects before and after mnemonic training. ² Findings showed that mnemonics created connectivity changes in the control group similar to memory athletes at baseline. These changes persisted for as long as 4 months after training, demonstrating that mnemonics have long-lasting effects on memory capacity. ²  

The most frequently used forms of medical mnemonics are acronyms or acrostics. Acronyms are words in which each letter in the word corresponds to a series of words to be remembered. ³ A familiar example of a medical acronym is “SLUDGE,” which represents the symptoms for cholinergic toxicity (salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis). An acrostic involves a phrase in which the first letter of each word corresponds to the first letter of a word to be remembered. ³ A commonly used acrostic phrase for the memorization of the 12 cranial nerves is “On Old Olympus’ Towering Tops A Finn And German Viewed Some Hops”: olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, auditory (vestibulocochlear), glossopharyngeal, vagus, spinal accessory, hypoglossal.

Mnemonics are an effective way for medical students, residents, and current practitioners to effortlessly recall information. For example, COVERABCD is an acronym that stands for circulation/capnograph/color, oxygen, ventilation, endotracheal tube, review of equipment, airway, breathing, circulation, and drugs. ⁴ Runciman et al showed that the use of the acronym COVERABCD could have prevented or mitigated 60% of 2000 anesthetic incidents. ⁴ Another mnemonic, FAST, used to assess for a stroke, reduced median hospital arrival times by more than an hour. ⁵    

There are hundreds of mnemonics related to medical practice. Collections of those that might be useful for family practitioners and medical residents can be found at the following links: 

https://epomedicine.com/medical-mnemonics/  

www.oxfordmedicaleducation.com/medical-mnemonics/  

Kristyn McKnight, PharmD candidate
Hannah Lutz, PharmD candidate
Tracy Mahvan, MBA, PharmD, BCGP
School of Pharmacy, University of Wyoming, Laramie

Mnemonics are often used to help remember complex groups of individual items related to a common theme. Studies have shown that college students studying with mnemonics outperform students using rote learning, suggesting that mnemonics are useful in retention of facts. ¹

In 1 study, researchers compared memory athletes and control subjects before and after mnemonic training. ² Findings showed that mnemonics created connectivity changes in the control group similar to memory athletes at baseline. These changes persisted for as long as 4 months after training, demonstrating that mnemonics have long-lasting effects on memory capacity. ²  

The most frequently used forms of medical mnemonics are acronyms or acrostics. Acronyms are words in which each letter in the word corresponds to a series of words to be remembered. ³ A familiar example of a medical acronym is “SLUDGE,” which represents the symptoms for cholinergic toxicity (salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis). An acrostic involves a phrase in which the first letter of each word corresponds to the first letter of a word to be remembered. ³ A commonly used acrostic phrase for the memorization of the 12 cranial nerves is “On Old Olympus’ Towering Tops A Finn And German Viewed Some Hops”: olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, auditory (vestibulocochlear), glossopharyngeal, vagus, spinal accessory, hypoglossal.

Mnemonics are an effective way for medical students, residents, and current practitioners to effortlessly recall information. For example, COVERABCD is an acronym that stands for circulation/capnograph/color, oxygen, ventilation, endotracheal tube, review of equipment, airway, breathing, circulation, and drugs. ⁴ Runciman et al showed that the use of the acronym COVERABCD could have prevented or mitigated 60% of 2000 anesthetic incidents. ⁴ Another mnemonic, FAST, used to assess for a stroke, reduced median hospital arrival times by more than an hour. ⁵    

There are hundreds of mnemonics related to medical practice. Collections of those that might be useful for family practitioners and medical residents can be found at the following links: 

https://epomedicine.com/medical-mnemonics/  

www.oxfordmedicaleducation.com/medical-mnemonics/  

Kristyn McKnight, PharmD candidate
Hannah Lutz, PharmD candidate
Tracy Mahvan, MBA, PharmD, BCGP
School of Pharmacy, University of Wyoming, Laramie

THE CASE

A 23-year-old woman with past medical history of bipolar II disorder and a REM-specific seizure disorder that resolved at age 9 presented after a syncopal episode. The patient reported an initial sensation of lightheadedness while at work, which was followed by a syncopal episode with brief (1-2 min) loss of consciousness and a minor head injury.

She denied other prodromal symptoms including chest pain, shortness of breath, ­palpitations, and nausea. She also did not experience convulsions, urinary/bowel incontinence, or confusion upon regaining consciousness.

She denied previous syncopal episodes. However, she reported that, 2 weeks prior, there had been an event similar to that of her presenting complaint. During that episode, she experienced lightheadedness and a fall without loss of consciousness.

The patient had been prescribed a regimen of sertraline 100 mg/d and aripiprazole 10 mg/d to maintain mood stability. She had self-discontinued these medications about 8 months prior to presentation. A recent return of her depressive features had prompted a restart of this regimen 1 week before her first fall, without an initial taper upward.

While in the emergency department, she became bradycardic (heart rate, 38 beats/min) and hypotensive (blood pressure, 70/40 mm Hg). She subsequently became increasingly somnolent and had 1 episode of emesis. An electrocardiogram (EKG) revealed sinus bradycardia without other acute abnormalities (FIGURE).

Blood work including a basic metabolic panel, complete blood count, and cardiac enzymes were all within normal limits. Computed tomography of the head revealed no intracranial pathology. Her vitals were initially unresponsive to a fluid bolus but improved and stabilized after administration of intravenous atropine 0.5 mg.

Aripiprazole was held and sertraline was decreased to 75 mg on hospital Day 1, with close monitoring of her mood. Cardiology was consulted and followed the patient ­during her stay. The patient was monitored on telemetry for 3 days, exhibiting only sinus ­bradycardia with a stable heart rate of 45-55 beats/min. Systolic blood pressures were ­stable within 120 to 130 mm Hg. Transthoracic echocardiogram performed on hospital Day 2 was unremarkable, revealing a normal left ventricular ejection fraction of 65% and no wall motion abnormalities. She had no recurrence of the syncope or emesis.

Continue to: THE DIAGNOSIS

Given her benign cardiac work-up and symptom onset coinciding with the abrupt resumption of high doses of aripiprazole after an 8-month abstinence, the patient’s presentation was attributed to a rather uncommon adverse drug reaction to aripiprazole. This has only been described in a few case reports.

DISCUSSION

Aripiprazole (Abilify) is an atypical antipsychotic frequently used in the treatment of psychiatric conditions, including bipolar disorder and schizophrenia. While the specific therapeutic mechanism is unknown, it is believed that drug efficacy is related to partial agonism at dopamine D₂, serotonin 5-HT_1A, and serotonin 5-HT_2A.¹ As aripiprazole works on a variety of receptors involved in other physiologic processes, clinical adverse effects have been reported, most of which are associated with the adrenergic alpha₁ receptors.¹ These include cognitive impairment and seizures. Cardiovascular adverse effects of aripiprazole include orthostatic hypotension, cardiac arrhythmia, prolonged QT interval, and syncope.^1-5

Family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms.

Selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) have also been shown to cause cardiac arrhythmia and syncope.⁶ Although sertraline may have contributed to the patient’s cardiac symptoms, it is more likely that the aripiprazole was the direct cause, as she remained asymptomatic while on a therapeutic dose of sertraline. Furthermore, aripiprazole is primarily metabolized though hepatic CYP2D6, which sertraline has been shown to inhibit.^1,7 Therefore, the concomitant use of sertraline with no initial taper of either medication likely led to an increased effective dose of aripiprazole in our patient and subsequently to her presentation.

Few prior cases have identified aripiprazole as a cause of antipsychotic-associated bradycardic response.⁸ Based on the Adverse Drug Reaction Probability Scale, often referred to as the Naranjo Scale, we believe this to be a probable adverse response in our patient.⁹ Bradycardia followed a reasonable temporal sequence after aripiprazole use with a response previously described in the literature. Symptoms also improved after discontinuation of the drug and other etiologies of the bradycardia were ruled out.

Our patient was discharged with a 30-day cardiac event monitor and a scheduled appointment with Cardiology.

Continue to: THE TAKEAWAY

As this case suggests, there may be an association between aripiprazole and symptomatic bradycardia. Therefore, family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms and consider tapering this medication if other causes cannot be identified. Additionally, given the potential cardiac adverse effects of atypical antipsychotics, physicians may consider ordering baseline and follow-up EKGs to monitor for arrhythmias in patients prescribed aripiprazole. This may be especially prudent when an atypical antipsychotic is combined with an SSRI, as potential cardiac adverse effects may occur more frequently.

CORRESPONDENCE
Kyle Fletke, MD, Department of Family and Community Medicine, University of Maryland School of Medicine, 29 South Paca Street, Baltimore, MD 21201; kfletke@som.umaryland.edu

THE CASE

A 23-year-old woman with past medical history of bipolar II disorder and a REM-specific seizure disorder that resolved at age 9 presented after a syncopal episode. The patient reported an initial sensation of lightheadedness while at work, which was followed by a syncopal episode with brief (1-2 min) loss of consciousness and a minor head injury.

She denied other prodromal symptoms including chest pain, shortness of breath, ­palpitations, and nausea. She also did not experience convulsions, urinary/bowel incontinence, or confusion upon regaining consciousness.

She denied previous syncopal episodes. However, she reported that, 2 weeks prior, there had been an event similar to that of her presenting complaint. During that episode, she experienced lightheadedness and a fall without loss of consciousness.

The patient had been prescribed a regimen of sertraline 100 mg/d and aripiprazole 10 mg/d to maintain mood stability. She had self-discontinued these medications about 8 months prior to presentation. A recent return of her depressive features had prompted a restart of this regimen 1 week before her first fall, without an initial taper upward.

While in the emergency department, she became bradycardic (heart rate, 38 beats/min) and hypotensive (blood pressure, 70/40 mm Hg). She subsequently became increasingly somnolent and had 1 episode of emesis. An electrocardiogram (EKG) revealed sinus bradycardia without other acute abnormalities (FIGURE).

Blood work including a basic metabolic panel, complete blood count, and cardiac enzymes were all within normal limits. Computed tomography of the head revealed no intracranial pathology. Her vitals were initially unresponsive to a fluid bolus but improved and stabilized after administration of intravenous atropine 0.5 mg.

Aripiprazole was held and sertraline was decreased to 75 mg on hospital Day 1, with close monitoring of her mood. Cardiology was consulted and followed the patient ­during her stay. The patient was monitored on telemetry for 3 days, exhibiting only sinus ­bradycardia with a stable heart rate of 45-55 beats/min. Systolic blood pressures were ­stable within 120 to 130 mm Hg. Transthoracic echocardiogram performed on hospital Day 2 was unremarkable, revealing a normal left ventricular ejection fraction of 65% and no wall motion abnormalities. She had no recurrence of the syncope or emesis.

Continue to: THE DIAGNOSIS

Given her benign cardiac work-up and symptom onset coinciding with the abrupt resumption of high doses of aripiprazole after an 8-month abstinence, the patient’s presentation was attributed to a rather uncommon adverse drug reaction to aripiprazole. This has only been described in a few case reports.

DISCUSSION

Aripiprazole (Abilify) is an atypical antipsychotic frequently used in the treatment of psychiatric conditions, including bipolar disorder and schizophrenia. While the specific therapeutic mechanism is unknown, it is believed that drug efficacy is related to partial agonism at dopamine D₂, serotonin 5-HT_1A, and serotonin 5-HT_2A.¹ As aripiprazole works on a variety of receptors involved in other physiologic processes, clinical adverse effects have been reported, most of which are associated with the adrenergic alpha₁ receptors.¹ These include cognitive impairment and seizures. Cardiovascular adverse effects of aripiprazole include orthostatic hypotension, cardiac arrhythmia, prolonged QT interval, and syncope.^1-5

Family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms.

Selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) have also been shown to cause cardiac arrhythmia and syncope.⁶ Although sertraline may have contributed to the patient’s cardiac symptoms, it is more likely that the aripiprazole was the direct cause, as she remained asymptomatic while on a therapeutic dose of sertraline. Furthermore, aripiprazole is primarily metabolized though hepatic CYP2D6, which sertraline has been shown to inhibit.^1,7 Therefore, the concomitant use of sertraline with no initial taper of either medication likely led to an increased effective dose of aripiprazole in our patient and subsequently to her presentation.

Few prior cases have identified aripiprazole as a cause of antipsychotic-associated bradycardic response.⁸ Based on the Adverse Drug Reaction Probability Scale, often referred to as the Naranjo Scale, we believe this to be a probable adverse response in our patient.⁹ Bradycardia followed a reasonable temporal sequence after aripiprazole use with a response previously described in the literature. Symptoms also improved after discontinuation of the drug and other etiologies of the bradycardia were ruled out.

Our patient was discharged with a 30-day cardiac event monitor and a scheduled appointment with Cardiology.

Continue to: THE TAKEAWAY

As this case suggests, there may be an association between aripiprazole and symptomatic bradycardia. Therefore, family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms and consider tapering this medication if other causes cannot be identified. Additionally, given the potential cardiac adverse effects of atypical antipsychotics, physicians may consider ordering baseline and follow-up EKGs to monitor for arrhythmias in patients prescribed aripiprazole. This may be especially prudent when an atypical antipsychotic is combined with an SSRI, as potential cardiac adverse effects may occur more frequently.

CORRESPONDENCE
Kyle Fletke, MD, Department of Family and Community Medicine, University of Maryland School of Medicine, 29 South Paca Street, Baltimore, MD 21201; kfletke@som.umaryland.edu

THE CASE

A 23-year-old woman with past medical history of bipolar II disorder and a REM-specific seizure disorder that resolved at age 9 presented after a syncopal episode. The patient reported an initial sensation of lightheadedness while at work, which was followed by a syncopal episode with brief (1-2 min) loss of consciousness and a minor head injury.

She denied other prodromal symptoms including chest pain, shortness of breath, ­palpitations, and nausea. She also did not experience convulsions, urinary/bowel incontinence, or confusion upon regaining consciousness.

She denied previous syncopal episodes. However, she reported that, 2 weeks prior, there had been an event similar to that of her presenting complaint. During that episode, she experienced lightheadedness and a fall without loss of consciousness.

The patient had been prescribed a regimen of sertraline 100 mg/d and aripiprazole 10 mg/d to maintain mood stability. She had self-discontinued these medications about 8 months prior to presentation. A recent return of her depressive features had prompted a restart of this regimen 1 week before her first fall, without an initial taper upward.

While in the emergency department, she became bradycardic (heart rate, 38 beats/min) and hypotensive (blood pressure, 70/40 mm Hg). She subsequently became increasingly somnolent and had 1 episode of emesis. An electrocardiogram (EKG) revealed sinus bradycardia without other acute abnormalities (FIGURE).

Blood work including a basic metabolic panel, complete blood count, and cardiac enzymes were all within normal limits. Computed tomography of the head revealed no intracranial pathology. Her vitals were initially unresponsive to a fluid bolus but improved and stabilized after administration of intravenous atropine 0.5 mg.

Aripiprazole was held and sertraline was decreased to 75 mg on hospital Day 1, with close monitoring of her mood. Cardiology was consulted and followed the patient ­during her stay. The patient was monitored on telemetry for 3 days, exhibiting only sinus ­bradycardia with a stable heart rate of 45-55 beats/min. Systolic blood pressures were ­stable within 120 to 130 mm Hg. Transthoracic echocardiogram performed on hospital Day 2 was unremarkable, revealing a normal left ventricular ejection fraction of 65% and no wall motion abnormalities. She had no recurrence of the syncope or emesis.

Continue to: THE DIAGNOSIS

Given her benign cardiac work-up and symptom onset coinciding with the abrupt resumption of high doses of aripiprazole after an 8-month abstinence, the patient’s presentation was attributed to a rather uncommon adverse drug reaction to aripiprazole. This has only been described in a few case reports.

DISCUSSION

Aripiprazole (Abilify) is an atypical antipsychotic frequently used in the treatment of psychiatric conditions, including bipolar disorder and schizophrenia. While the specific therapeutic mechanism is unknown, it is believed that drug efficacy is related to partial agonism at dopamine D₂, serotonin 5-HT_1A, and serotonin 5-HT_2A.¹ As aripiprazole works on a variety of receptors involved in other physiologic processes, clinical adverse effects have been reported, most of which are associated with the adrenergic alpha₁ receptors.¹ These include cognitive impairment and seizures. Cardiovascular adverse effects of aripiprazole include orthostatic hypotension, cardiac arrhythmia, prolonged QT interval, and syncope.^1-5

Family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms.

Selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) have also been shown to cause cardiac arrhythmia and syncope.⁶ Although sertraline may have contributed to the patient’s cardiac symptoms, it is more likely that the aripiprazole was the direct cause, as she remained asymptomatic while on a therapeutic dose of sertraline. Furthermore, aripiprazole is primarily metabolized though hepatic CYP2D6, which sertraline has been shown to inhibit.^1,7 Therefore, the concomitant use of sertraline with no initial taper of either medication likely led to an increased effective dose of aripiprazole in our patient and subsequently to her presentation.

Few prior cases have identified aripiprazole as a cause of antipsychotic-associated bradycardic response.⁸ Based on the Adverse Drug Reaction Probability Scale, often referred to as the Naranjo Scale, we believe this to be a probable adverse response in our patient.⁹ Bradycardia followed a reasonable temporal sequence after aripiprazole use with a response previously described in the literature. Symptoms also improved after discontinuation of the drug and other etiologies of the bradycardia were ruled out.

Our patient was discharged with a 30-day cardiac event monitor and a scheduled appointment with Cardiology.

Continue to: THE TAKEAWAY

As this case suggests, there may be an association between aripiprazole and symptomatic bradycardia. Therefore, family physicians should inquire about aripiprazole use in patients who present with cardiac symptoms and consider tapering this medication if other causes cannot be identified. Additionally, given the potential cardiac adverse effects of atypical antipsychotics, physicians may consider ordering baseline and follow-up EKGs to monitor for arrhythmias in patients prescribed aripiprazole. This may be especially prudent when an atypical antipsychotic is combined with an SSRI, as potential cardiac adverse effects may occur more frequently.

CORRESPONDENCE
Kyle Fletke, MD, Department of Family and Community Medicine, University of Maryland School of Medicine, 29 South Paca Street, Baltimore, MD 21201; kfletke@som.umaryland.edu

Sarcoidosis is a multisystem inflammatory disease of unclear etiology that primarily affects the lungs. It can occur at any age but usually develops before the age of 50 years, with an initial peak incidence at 20 to 29 years and a second peak incidence after 50 years of age, especially among women in Scandinavia and Japan.¹ Sarcoidosis affects men and women of all racial and ethnic groups throughout the world, but differences based on race, sex, and geography are noted.¹

The highest rates are reported in northern European and African-American individuals, particularly in women.^1,2 The adjusted annual incidence of sarcoidosis among African Americans is approximately 3 times that among White Americans³ and is more likely to be chronic and fatal in African Americans.³ The disease can be familial with a possible recessive inheritance mode with incomplete penetrance.⁴ Risk of sarcoidosis in monozygotic twins appears to be 80 times greater than that in the general population, which supports genetic factors accounting for two-thirds of disease susceptibility.⁵

Likely factors in the development of sarcoidosis

The exact cause of sarcoidosis is unknown, but we have insights into its pathogenesis and potential triggers.^1,6-9 Genes involved are being identified: class I and II human leukocyte antigen (HLA) molecules are most consistently associated with risk of sarcoidosis. Environmental exposures can activate the innate immune system and precondition a susceptible individual to react to potential causative antigens in a highly polarized, antigen-specific Th1 immune response. The epithelioid granulomatous response involves local proinflammatory cytokine production and enhanced T-cell immunity at sites of inflammation.¹⁰ Granulomas generally form to confine pathogens, restrict inflammation, and protect surrounding tissue.^11-13

Sarcoidosis is a diagnosis of exclusion; one must rule out infections, occupational or environmental exposures, malignancies, and other disorders that cause granulomatous inflammation.

ACCESS (A Case Control Etiologic Study of Sarcoidosis) identified several environmental exposures such as chemicals used in the agriculture industry, mold or mildew, and musty odors at work.¹⁴ Tobacco use was not associated with sarcoidosis.¹⁴ Recent studies have shown positive associations with service in the US Navy,¹⁵ metal working,¹⁶ firefighting,¹⁷ the handling of building supplies,¹⁸ and onsite exposure while assisting in rescue efforts at the World Trade Center disaster.¹⁹ Other data support the likelihood that specific environmental exposures associated with microbe-rich environments modestly increase the risk of sarcoidosis.¹⁴ Mycobacterial and propionibacterial DNA and RNA are potentially associated with sarcoidosis.²⁰

Clinical manifestations are nonspecific

The diagnosis of sarcoidosis can be difficult and delayed due to diverse organ involvement and nonspecific presentations. TABLE 1^21-31 shows the diverse manifestations in a patient with suspected sarcoidosis. Around 50% of the patients are asymptomatic.^23,24 Sarcoidosis is a diagnosis of exclusion, starting with a detailed history to rule out infections, occupational or environmental exposures, malignancies, and other possible disorders (TABLE 2).²²

Diagnostic work-up

The primary objective of a diagnostic evaluation in most suspected cases of sarcoidosis is to corroborate the clinical and radiologic features with pathologic evidence of non-necrotizing granulomas and to exclude other causes of granulomatous inflammation.²²

Radiologic studies

Chest x-ray (CXR) provides diagnostic and prognostic information in the evaluation of sarcoidosis using the Scadding classification system (FIGURE 1).^21,25,32,33 Interobserver variability, especially between stages II and III and III and IV is the major limitation of this system.³² At presentation, radiographs are abnormal in approximately 90% of patients.³⁴ Lymphadenopathy is the most common radiographic abnormality, occurring in more than two-thirds of cases, and pulmonary opacities (nodules and reticulation) with a middle to upper lobe predilection are present in 20% to 50% of patients.^1,31,35 The nodules vary in size and can coalesce and cause alveolar collapse, thus producing consolidation.³⁶ Linear opacities radiating laterally from the hilum into the middle and upper zones are characteristic in fibrotic disease.

Continue to: High-resoluton computed tomography

High-resolution computed tomography (HRCT). Micronodules in a perilymphatic distribution with upper lobe predominance combined with subcarinal and symmetrical hilar lymph node enlargement is practically diagnostic of sarcoidosis in the right clinical context. TABLE 3^21,23,25,32 and FIGURE 2^21,23,25,32 summarize the common CT chest findings of sarcoidosis.

Advanced imaging such as (18)F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) are used in specialized settings for advanced pulmonary, cardiac, or neurosarcoidosis.

Tissue biopsy

Skin lesions (other than erythema nodosum), eye lesions, and peripheral lymph nodes are considered the safest extrapulmonary locations for biopsy.^21,25 If pulmonary infiltrates or lymphadenopathy are present, or if extrapulmonary biopsy sites are not available, then flexible bronchoscopy with biopsy is the mainstay for tissue sampling.²⁵

Bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), endobronchial biopsy (EBB), and endobronchial ultrasound (EBUS) are invaluable modalities that have reduced the need for open lung biopsy. BAL in sarcoidosis can show lymphocytosis > 15% (nonspecific) and a CD4:CD8 lymphocyte ratio > 3.5 (specificity > 90%).^21,22 TBB is more sensitive than EBB; however, sensitivity overall is heightened when both of them are combined. The advent of EBUS has increased the safety and efficiency of needle aspiration of mediastinal lymph nodes. Diagnostic yield of EBUS (~80%) is superior to that with TBB and EBB (~50%), especially in stage I and II sarcoidosis.³⁷ The combination of EBUS with TBB improves the diagnostic yield to ~90%.³⁷

The decision to obtain biopsy samples hinges on the nature of clinical and radiologic findings (FIGURE 3).^22,25,26

Continue to: Laboratory studies

Multiple abnormalities may be seen in sarcoidosis, and specific lab tests may help support a diagnosis of sarcoidosis or detect organ-specific disease activity (TABLE 4).^22,23,25,38 However, no consistently accurate biomarkers exist for use in clinical practice. An angiotensin-converting enzyme (ACE) level greater than 2 times the upper limit of normal may be helpful; however, sensitivity remains low, and genetic polymorphisms can influence the ACE level.²⁵ Biomarkers sometimes used to assess disease activity are serum interleukin-2 receptor, neopterin, chitotriosidase, lysozyme, KL-6 glycoprotein, and amyloid A.²¹

Additional tests to assess specific features or organ involvement

Pulmonary function testing (PFT) is reviewed in detail below under “pulmonary sarcoidosis.”

Electrocardiogram (EKG)/transthoracic echocardiogram (TTE). EKG abnormalities—conduction disturbances, arrhythmias, or nonspecific ST segment and T-wave changes—are the most common nonspecific findings.³⁰ TTE findings are also nonspecific but have value in assessing cardiac chamber size and function and myocardial involvement. TTE is indeed the most common screening modality for sarcoidosis-associated pulmonary hypertension (SAPH), which is definitively diagnosed by right heart catheterization (RHC). Further evaluation for cardiac sarcoidosis can be done with cardiac MRI or fluorodeoxyglucose PET in specialized settings.

Lumbar puncture (LP) may reveal lymphocytic infiltration in suspected neurosarcoidosis, but the finding is nonspecific and can reflect infection or malignancy. Oligoclonal bands may also be seen in about one-third of neurosarcoidosis cases, and it is imperative to rule out multiple sclerosis.²⁸

Pulmonary sarcoidosis

Pulmonary sarcoidosis accounts for most of the morbidity, mortality, and health care use associated with sarcoidosis.^39,40

Continue to: Pathology of early and advanced pulmonary sarcoidosis

Pathology of early and advanced pulmonary sarcoidosis

Sarcoidosis is characterized by coalescing, tightly clustered, nonnecrotizing granulomas in the lung (FIGURE 4), most often located along the lymphatic routes of the pleura, interlobular septa, and bronchovascular bundles.⁴¹ Granulomas contain epithelioid cells or multinucleated giant cells surrounded by a chronic lymphocytic infiltrate. Typically, intracytoplasmic inclusions, such as Schaumann bodies, asteroid bodies, and blue bodies of calcium oxalates are noted within giant cells.

In chronic disease, lymphocytic infiltrate vanishes and granulomas tend to become increasingly fibrotic and enlarge to form hyalinized nodules rich with densely eosinophilic collagen. In 10% to 30% of cases, the lungs undergo progressive fibrosis.⁴⁰ Nonresolving inflammation appears to be the major cause of fibrosis and the peribronchovascular localization leading to marked bronchial distortion.

Clinical features, monitoring, and outcomes

Pulmonary involvement occurs in most patients with sarcoidosis, and subclinical pulmonary disease is generally present, even when extrathoracic manifestations predominate.²³ Dry cough, dyspnea, and chest discomfort are the most common symptoms. Chest auscultation is usually unremarkable. Wheezing is more common in those with fibrosis and is attributed to airway-centric fibrosis.⁴² There is often a substantial delay between the onset of symptoms and the diagnosis of pulmonary sarcoidosis, as symptoms are nonspecific and might be mistaken for more common pulmonary diseases, such as asthma or chronic bronchitis.⁴³

Since sarcoidosis can affect pulmonary parenchyma, interstitium, large and small airways, pulmonary vasculature, and respiratory muscles, the pattern of lung function impairment on PFT varies from normal to obstruction, restriction, isolated diffusion defect, or a combination of these. The typical physiologic abnormality is a restrictive ventilatory defect with a decreased diffusing capacity of the lung for carbon monoxide (DLCO). Extent of disease seen on HRCT correlates with level of restriction.⁴⁴ Airway obstruction can be multifactorial and due to airway distortion (more likely to occur in fibrotic lung disease) and luminal disease.^45-48 The 6-minute walk test and DLCO can also aid in the diagnosis of SAPH and advanced parenchymal lung disease.

While monitoring is done clinically and with testing (PFT and imaging) as needed, the optimal approach is unclear. Nevertheless, longitudinal monitoring with testing may provide useful management and prognostic information.⁴⁰ Pulmonary function can remain stable in fibrotic sarcoidosis over extended periods and actually can improve in some patients.⁴⁹ Serial spirometry, particularly forced vital capacity, is the most reliable tool for monitoring; when a decline in measurement occurs, chest radiography can elucidate the mechanism.^50,51

Continue to: Because sarcoidosis is a multisystem disease...

Because sarcoidosis is a multisystem disease, caution needs to be exercised when evaluating a patient’s new or worsening respiratory symptoms to accurately determine the cause of symptoms and direct therapy accordingly. In addition to refractory inflammatory pulmonary disease, airway disease, infection, fibrosis, and SAPH, one needs to consider extrapulmonary involvement or complications such as cardiac or neurologic disease, musculoskeletal disease, depression, or fatigue. Adverse medication effects, deconditioning, or unrelated (or possibly related) disorders (eg pulmonary embolism) may be to blame.

Determining prognosis

Prognosis of sarcoidosis varies and depends on epidemiologic factors, clinical presentation, and course, as well as specific organ involvement. Patients may develop life-threatening pulmonary, cardiac, or neurologic complications. End-stage disease may require organ transplantation for eligible patients.

Most patients with pulmonary sarcoidosis experience clinical remission with minimal residual organ impairment and a favorable long-term outcome. Advanced pulmonary disease (known as APS) occurs in a small proportion of patients with sarcoidosis but accounts for most of the poor outcomes in sarcoidosis.⁴⁰ APS is variably defined, but it generally includes pulmonary fibrosis, SAPH, and respiratory infection.

One percent to 5% of patients with sarcoidosis die from complications, and mortality is higher in women and African Americans.⁵² Mortality and morbidity may be increasing.⁵³ The reasons behind these trends are unclear but could include true increases in disease incidence, better detection rates, greater severity of disease, or an aging population. Increased hospitalizations and health care use might be due to organ damage from granulomatous inflammation (and resultant fibrosis), complications associated with treatment, and psychosocial effects of the disease/treatment.

Management

Management consists primarily of anti-­inflammatory or immunosuppressive therapies but can also include measures to address specific complications (such as fatigue) and organ transplant, as well as efforts to counter adverse medication effects. Other supportive and preventive measures may include, on a case-by-case basis, oxygen supplementation, vaccinations, or pulmonary rehabilitation. Details of these are found in other, more in-depth reviews on treatment; we will briefly review anti-inflammatory therapy, which forms the cornerstone of treatment in most patients with sarcoidosis.

Continue to: General approach to treatment decisions

General approach to treatment decisions. Anti-inflammatory therapy is used to reduce granulomatous inflammation, thereby preserving organ function and reducing symptoms. A decision to begin treatment is one shared with the patient and is based on symptoms and potential danger of organ system failure.⁵⁴ Patients who are symptomatic or have progressive disease or physiologic impairment are generally candidates for treatment. Monitoring usually suffices for those who have minimal symptoms, stable disease, and preserved organ function.

Patients with pulmonary sarcoidosis at CXR stage 0 should not receive treatment, given that large, randomized trials have shown no meaningful benefit and that these patients have a high likelihood of spontaneous remission and excellent long-term prognosis.^55-58 However, a subgroup of patients classified as stage 0/I on CXR may show parenchymal disease on HRCT,⁵⁹ and, if more symptomatic, could be considered for treatment. For patients with stage II to IV pulmonary sarcoidosis with symptoms, there is good evidence that treatment may improve lung function and reduce dyspnea and fatigue.^57,60-62

Corticosteroids are first-line treatment for most patients. Based on expert opinion, treatment of pulmonary sarcoidosis is generally started with oral prednisone (or an equivalent corticosteroid). A starting dose of 20 to 40 mg/d generally is sufficient for most patients. If the patient responds to initial treatment, prednisone dose is tapered over a period of months. If symptoms worsen during tapering, the minimum effective dose is maintained without further attempts at tapering. Treatment is continued for at least 3 to 6 months but it might be needed for longer durations; unfortunately, evidence-based guidelines are lacking.⁶³ Once the patient goes into remission, close monitoring is done for possible relapses. Inhaled corticosteroids alone have not reduced symptoms or improved lung function in patients with pulmonary sarcoidosis.^64-66

Steroid-sparing agents are added for many patients. For patients receiving chronic prednisone therapy (≥ 10 mg for > 6 months), steroid-sparing agents are considered to minimize the adverse effects of steroids or to better control the inflammatory activity of sarcoidosis. These agents must be carefully selected, and clinical and laboratory monitoring need to be done throughout therapy. TABLE 5^58,64,67-81shows the major anti-inflammatory treatment agents used for sarcoidosis.

The management might be complicated for extrapulmonary, multi-organ, and advanced sarcoidosis (advanced pulmonary sarcoidosis, cardiac disease, neurosarcoidosis, lupus pernio, etc) when specialized testing, as well as a combination of corticosteroids and steroid-sparing agents (with higher doses or prolonged courses), might be needed. This should be performed at an expert sarcoidosis center, ideally in a multidisciplinary setting involving pulmonologists and/or rheumatologists, chest radiologists, and specialists as indicated, based on specific organ involvement.

Continue to: Research and future directions

Research and future directions

Key goals for research are identifying more accurate biomarkers of disease, improving diagnosis of multi-organ disease, determining validated endpoints of clinical trials in sarcoidosis, and developing treatments for refractory cases.

There is optimism and opportunity in the field of sarcoidosis overall. An example of an advancement is in the area of APS, as the severity and importance of this phenotype has been better understood. Worldwide registries and trials of pulmonary vasodilator therapy (bosentan, sildenafil, epoprostenol, and inhaled iloprost) in patients with SAPH without left ventricular dysfunction are promising.^82-85 However, no benefit in survival has been shown.

RioSAPH is a double-blind, placebo-controlled trial of Riociguat (a stimulator of soluble guanylate cyclase) for SAPH (NCT02625558) that is closed to enrollment and undergoing data review. Similarly, results of the phase IV study of pirfenidone, an antifibrotic agent that was shown to decrease disease progression and deaths in idiopathic pulmonary fibrosis,⁸⁶ are awaited in the near future.

Other potential directions being explored are multicenter patient registries and randomized controlled trials, analyses of existing databases, use of biobanking, and patient-centered outcome measures. Hopefully, the care of patients with sarcoidosis will become more evidence based with ongoing and upcoming research in this field.

CORRESPONDENCE
Rohit Gupta, MBBS, FCCP, 3401 North Broad Street, 7 Parkinson Pavilion, Philadelphia, PA 19140; rohit.gupta@tuhs.temple.edu

Sarcoidosis is a multisystem inflammatory disease of unclear etiology that primarily affects the lungs. It can occur at any age but usually develops before the age of 50 years, with an initial peak incidence at 20 to 29 years and a second peak incidence after 50 years of age, especially among women in Scandinavia and Japan.¹ Sarcoidosis affects men and women of all racial and ethnic groups throughout the world, but differences based on race, sex, and geography are noted.¹

The highest rates are reported in northern European and African-American individuals, particularly in women.^1,2 The adjusted annual incidence of sarcoidosis among African Americans is approximately 3 times that among White Americans³ and is more likely to be chronic and fatal in African Americans.³ The disease can be familial with a possible recessive inheritance mode with incomplete penetrance.⁴ Risk of sarcoidosis in monozygotic twins appears to be 80 times greater than that in the general population, which supports genetic factors accounting for two-thirds of disease susceptibility.⁵

Likely factors in the development of sarcoidosis

The exact cause of sarcoidosis is unknown, but we have insights into its pathogenesis and potential triggers.^1,6-9 Genes involved are being identified: class I and II human leukocyte antigen (HLA) molecules are most consistently associated with risk of sarcoidosis. Environmental exposures can activate the innate immune system and precondition a susceptible individual to react to potential causative antigens in a highly polarized, antigen-specific Th1 immune response. The epithelioid granulomatous response involves local proinflammatory cytokine production and enhanced T-cell immunity at sites of inflammation.¹⁰ Granulomas generally form to confine pathogens, restrict inflammation, and protect surrounding tissue.^11-13

Sarcoidosis is a diagnosis of exclusion; one must rule out infections, occupational or environmental exposures, malignancies, and other disorders that cause granulomatous inflammation.

ACCESS (A Case Control Etiologic Study of Sarcoidosis) identified several environmental exposures such as chemicals used in the agriculture industry, mold or mildew, and musty odors at work.¹⁴ Tobacco use was not associated with sarcoidosis.¹⁴ Recent studies have shown positive associations with service in the US Navy,¹⁵ metal working,¹⁶ firefighting,¹⁷ the handling of building supplies,¹⁸ and onsite exposure while assisting in rescue efforts at the World Trade Center disaster.¹⁹ Other data support the likelihood that specific environmental exposures associated with microbe-rich environments modestly increase the risk of sarcoidosis.¹⁴ Mycobacterial and propionibacterial DNA and RNA are potentially associated with sarcoidosis.²⁰

Clinical manifestations are nonspecific

The diagnosis of sarcoidosis can be difficult and delayed due to diverse organ involvement and nonspecific presentations. TABLE 1^21-31 shows the diverse manifestations in a patient with suspected sarcoidosis. Around 50% of the patients are asymptomatic.^23,24 Sarcoidosis is a diagnosis of exclusion, starting with a detailed history to rule out infections, occupational or environmental exposures, malignancies, and other possible disorders (TABLE 2).²²