The Journal of Family Practice

In September 2022, the US Preventive Services Task Force (USPSTF) released 2 sets of draft recommendations on screening for 3 mental health conditions in adults: ­anxiety, depression, and suicide risk.^1,2 These draft recommendations are summarized in TABLE 1^1-4 along with finalized recommendations on the same topics for children and adolescents, published in October 2022.^3,4

The recommendations on depression and suicide risk screening in adults are updates of previous recommendations (2016 for depression and 2014 for suicide risk) with no major changes. Screening for anxiety is a topic addressed for the first time this year for adults and for children and adolescents.^1,3

The recommendations are fairly consistent between age groups. A “B” recommendation supports screening for major depression in all patients starting at age 12 years, including during pregnancy and the postpartum period. (See TABLE 1 for grade definitions.) For all age groups, evidence was insufficient to recommend screening for suicide risk. A “B” recommendation was also assigned to screening for anxiety in those ages 8 to 64 years. The USPSTF believes the evidence is insufficient to make a recommendation on screening for anxiety among adults ≥ 65 years of age.

The anxiety disorders common to both children and adults included in the USPSTF recommendations are generalized anxiety disorder, social anxiety disorder, panic disorder, separation anxiety disorder, phobias, selective mutism, and anxiety type not specified. For adults, the USPSTF also includes substance/medication-induced anxiety and anxiety due to other medical conditions.

Adults with anxiety often present with generalized complaints such as sleep disturbance, pain, and other somatic disorders that can remain undiagnosed for years. The ­USPSTF cites a lifetime prevalence of anxiety disorders of 26.4% for men and 40.4% for women, although the data used are 10 years old.⁵ The cited rate of generalized anxiety in pregnancy is 8.5% to 10.5%, and in the postpartum period, 4.4% to 10.8%.⁶

The data on direct benefits and harms of screening for anxiety in adults through age 64 are sparse. Nevertheless, the USPSTF deemed that screening tests for anxiety have adequate accuracy and that psychological interventions for anxiety result in moderate reduction of anxiety symptoms. Pharmacologic interventions produce a small benefit, although there is a lack of evidence for pharmacotherapy in pregnant and postpartum women. There is even less evidence of benefit for treatment in adults ≥ 65 years of age.¹

How anxiety screening tests compare

Screening tests for anxiety in adults reviewed by the USPSTF included the Generalized Anxiety Disorder (GAD) scale and the Edinburgh Postnatal Depression Scale (EPDS) anxiety subscale.¹ The most studied tools are the ­GAD-2 and GAD-7.

Continue to: The sensitivity and specificity...

The sensitivity and specificity of each test depends on the cutoff used. With the GAD-2, a cutoff of 2 or more resulted in a sensitivity of 94% and a specificity of 68% for detecting generalized anxiety.⁷ A cutoff of 3 or more resulted in a sensitivity of 81% and a specificity of 86%.⁷ The GAD-7, using 10 as a cutoff, achieves a sensitivity of 79% and a specificity of 89%.⁷ Given the similar performance of the 2 options, the GAD-2 (TABLE 2^8,9) is probably preferable for use in primary care because of its ease of administration.

The tests evaluated by the USPSTF for anxiety screening in children and adolescents ≥ 8 years of age included the Screen for Child Anxiety Related Disorders (SCARED) and the Patient Health Questionnaire–Adolescent (PHQ-A).³ These tools ask more questions than the adult screening tools do: 41 for the SCARED and 13 for the PHQ-A. The sensitivity of SCARED for generalized anxiety disorder was 64% and the specificity was 63%.¹⁰ The sensitivity of the PHQ-A was 50% and the specificity was 98%.¹⁰

Various versions of all of these screening tools can be easily located on the internet. Search for them using the acronyms.

Screening for major depression

The depression screening tests the USPSTF examined were various versions of the Patient Health Questionnaire (PHQ), the Center for Epidemiologic Studies Depression Scale ­(CES-D), the Geriatric Depression Scale (GDS) in older adults, and the EPDS in postpartum and pregnant persons.⁷

A 2-question version of the PHQ was found to have a sensitivity of 91% with a specificity of 67%. The 9-question PHQ was found to have a similar sensitivity (88%) but better specificity (85%).⁷TABLE 3¹¹ lists the 2 questions in the PHQ-2 and explains how to score the results.

Continue to: The most commonly...

The most commonly studied screening tool for adolescents is the PHQ-A. Its sensitivity is 73% and specificity is 94%.¹²

The GAD-2 and PHQ-2 have the same possible answers and scores and can be combined into a 4-question screening tool to assess for anxiety and depression. If an initial screen for anxiety or depression (or both) is positive, further diagnostic testing and follow-up are needed.

Frequency of screening

The USPSTF recognized that limited information on the frequency of screening for both anxiety and depression does not support any recommendation on this matter. It suggested screening everyone once and then basing the need for subsequent screening tests on clinical judgment after considering risk factors and life events, with periodic rescreening of those at high risk. Finally, USPSTF recognized the many challenges to implementing screening tests for mental health conditions in primary care practice, but offered little practical advice on how to do this.

Suicide risk screening

As for the evidence on benefits and harms of screening for suicide risk in all age groups, the USPSTF still regards it as insufficient to make a recommendation. The lack of evidence applies to all aspects of screening, including the accuracy of the various screening tools and the potential benefits and harms of preventive interventions.^2,7

Next steps

The recommendations on screening for depression, suicide risk, and anxiety in adults have been published as a draft, and the public comment period will be over by the time of this publication. The USPSTF generally takes 6 to 9 months to consider all the public comments and to publish final recommendations. The final recommendations on these topics for children and adolescents have been published since drafts were made available last April. There were no major changes between the draft and final versions.

In September 2022, the US Preventive Services Task Force (USPSTF) released 2 sets of draft recommendations on screening for 3 mental health conditions in adults: ­anxiety, depression, and suicide risk.^1,2 These draft recommendations are summarized in TABLE 1^1-4 along with finalized recommendations on the same topics for children and adolescents, published in October 2022.^3,4

The recommendations on depression and suicide risk screening in adults are updates of previous recommendations (2016 for depression and 2014 for suicide risk) with no major changes. Screening for anxiety is a topic addressed for the first time this year for adults and for children and adolescents.^1,3

The recommendations are fairly consistent between age groups. A “B” recommendation supports screening for major depression in all patients starting at age 12 years, including during pregnancy and the postpartum period. (See TABLE 1 for grade definitions.) For all age groups, evidence was insufficient to recommend screening for suicide risk. A “B” recommendation was also assigned to screening for anxiety in those ages 8 to 64 years. The USPSTF believes the evidence is insufficient to make a recommendation on screening for anxiety among adults ≥ 65 years of age.

The anxiety disorders common to both children and adults included in the USPSTF recommendations are generalized anxiety disorder, social anxiety disorder, panic disorder, separation anxiety disorder, phobias, selective mutism, and anxiety type not specified. For adults, the USPSTF also includes substance/medication-induced anxiety and anxiety due to other medical conditions.

Adults with anxiety often present with generalized complaints such as sleep disturbance, pain, and other somatic disorders that can remain undiagnosed for years. The ­USPSTF cites a lifetime prevalence of anxiety disorders of 26.4% for men and 40.4% for women, although the data used are 10 years old.⁵ The cited rate of generalized anxiety in pregnancy is 8.5% to 10.5%, and in the postpartum period, 4.4% to 10.8%.⁶

The data on direct benefits and harms of screening for anxiety in adults through age 64 are sparse. Nevertheless, the USPSTF deemed that screening tests for anxiety have adequate accuracy and that psychological interventions for anxiety result in moderate reduction of anxiety symptoms. Pharmacologic interventions produce a small benefit, although there is a lack of evidence for pharmacotherapy in pregnant and postpartum women. There is even less evidence of benefit for treatment in adults ≥ 65 years of age.¹

How anxiety screening tests compare

Screening tests for anxiety in adults reviewed by the USPSTF included the Generalized Anxiety Disorder (GAD) scale and the Edinburgh Postnatal Depression Scale (EPDS) anxiety subscale.¹ The most studied tools are the ­GAD-2 and GAD-7.

Continue to: The sensitivity and specificity...

The sensitivity and specificity of each test depends on the cutoff used. With the GAD-2, a cutoff of 2 or more resulted in a sensitivity of 94% and a specificity of 68% for detecting generalized anxiety.⁷ A cutoff of 3 or more resulted in a sensitivity of 81% and a specificity of 86%.⁷ The GAD-7, using 10 as a cutoff, achieves a sensitivity of 79% and a specificity of 89%.⁷ Given the similar performance of the 2 options, the GAD-2 (TABLE 2^8,9) is probably preferable for use in primary care because of its ease of administration.

The tests evaluated by the USPSTF for anxiety screening in children and adolescents ≥ 8 years of age included the Screen for Child Anxiety Related Disorders (SCARED) and the Patient Health Questionnaire–Adolescent (PHQ-A).³ These tools ask more questions than the adult screening tools do: 41 for the SCARED and 13 for the PHQ-A. The sensitivity of SCARED for generalized anxiety disorder was 64% and the specificity was 63%.¹⁰ The sensitivity of the PHQ-A was 50% and the specificity was 98%.¹⁰

Various versions of all of these screening tools can be easily located on the internet. Search for them using the acronyms.

Screening for major depression

The depression screening tests the USPSTF examined were various versions of the Patient Health Questionnaire (PHQ), the Center for Epidemiologic Studies Depression Scale ­(CES-D), the Geriatric Depression Scale (GDS) in older adults, and the EPDS in postpartum and pregnant persons.⁷

A 2-question version of the PHQ was found to have a sensitivity of 91% with a specificity of 67%. The 9-question PHQ was found to have a similar sensitivity (88%) but better specificity (85%).⁷TABLE 3¹¹ lists the 2 questions in the PHQ-2 and explains how to score the results.

Continue to: The most commonly...

The most commonly studied screening tool for adolescents is the PHQ-A. Its sensitivity is 73% and specificity is 94%.¹²

The GAD-2 and PHQ-2 have the same possible answers and scores and can be combined into a 4-question screening tool to assess for anxiety and depression. If an initial screen for anxiety or depression (or both) is positive, further diagnostic testing and follow-up are needed.

Frequency of screening

The USPSTF recognized that limited information on the frequency of screening for both anxiety and depression does not support any recommendation on this matter. It suggested screening everyone once and then basing the need for subsequent screening tests on clinical judgment after considering risk factors and life events, with periodic rescreening of those at high risk. Finally, USPSTF recognized the many challenges to implementing screening tests for mental health conditions in primary care practice, but offered little practical advice on how to do this.

Suicide risk screening

As for the evidence on benefits and harms of screening for suicide risk in all age groups, the USPSTF still regards it as insufficient to make a recommendation. The lack of evidence applies to all aspects of screening, including the accuracy of the various screening tools and the potential benefits and harms of preventive interventions.^2,7

Next steps

The recommendations on screening for depression, suicide risk, and anxiety in adults have been published as a draft, and the public comment period will be over by the time of this publication. The USPSTF generally takes 6 to 9 months to consider all the public comments and to publish final recommendations. The final recommendations on these topics for children and adolescents have been published since drafts were made available last April. There were no major changes between the draft and final versions.

In September 2022, the US Preventive Services Task Force (USPSTF) released 2 sets of draft recommendations on screening for 3 mental health conditions in adults: ­anxiety, depression, and suicide risk.^1,2 These draft recommendations are summarized in TABLE 1^1-4 along with finalized recommendations on the same topics for children and adolescents, published in October 2022.^3,4

The recommendations on depression and suicide risk screening in adults are updates of previous recommendations (2016 for depression and 2014 for suicide risk) with no major changes. Screening for anxiety is a topic addressed for the first time this year for adults and for children and adolescents.^1,3

The recommendations are fairly consistent between age groups. A “B” recommendation supports screening for major depression in all patients starting at age 12 years, including during pregnancy and the postpartum period. (See TABLE 1 for grade definitions.) For all age groups, evidence was insufficient to recommend screening for suicide risk. A “B” recommendation was also assigned to screening for anxiety in those ages 8 to 64 years. The USPSTF believes the evidence is insufficient to make a recommendation on screening for anxiety among adults ≥ 65 years of age.

The anxiety disorders common to both children and adults included in the USPSTF recommendations are generalized anxiety disorder, social anxiety disorder, panic disorder, separation anxiety disorder, phobias, selective mutism, and anxiety type not specified. For adults, the USPSTF also includes substance/medication-induced anxiety and anxiety due to other medical conditions.

Adults with anxiety often present with generalized complaints such as sleep disturbance, pain, and other somatic disorders that can remain undiagnosed for years. The ­USPSTF cites a lifetime prevalence of anxiety disorders of 26.4% for men and 40.4% for women, although the data used are 10 years old.⁵ The cited rate of generalized anxiety in pregnancy is 8.5% to 10.5%, and in the postpartum period, 4.4% to 10.8%.⁶

The data on direct benefits and harms of screening for anxiety in adults through age 64 are sparse. Nevertheless, the USPSTF deemed that screening tests for anxiety have adequate accuracy and that psychological interventions for anxiety result in moderate reduction of anxiety symptoms. Pharmacologic interventions produce a small benefit, although there is a lack of evidence for pharmacotherapy in pregnant and postpartum women. There is even less evidence of benefit for treatment in adults ≥ 65 years of age.¹

How anxiety screening tests compare

Screening tests for anxiety in adults reviewed by the USPSTF included the Generalized Anxiety Disorder (GAD) scale and the Edinburgh Postnatal Depression Scale (EPDS) anxiety subscale.¹ The most studied tools are the ­GAD-2 and GAD-7.

Continue to: The sensitivity and specificity...

The sensitivity and specificity of each test depends on the cutoff used. With the GAD-2, a cutoff of 2 or more resulted in a sensitivity of 94% and a specificity of 68% for detecting generalized anxiety.⁷ A cutoff of 3 or more resulted in a sensitivity of 81% and a specificity of 86%.⁷ The GAD-7, using 10 as a cutoff, achieves a sensitivity of 79% and a specificity of 89%.⁷ Given the similar performance of the 2 options, the GAD-2 (TABLE 2^8,9) is probably preferable for use in primary care because of its ease of administration.

The tests evaluated by the USPSTF for anxiety screening in children and adolescents ≥ 8 years of age included the Screen for Child Anxiety Related Disorders (SCARED) and the Patient Health Questionnaire–Adolescent (PHQ-A).³ These tools ask more questions than the adult screening tools do: 41 for the SCARED and 13 for the PHQ-A. The sensitivity of SCARED for generalized anxiety disorder was 64% and the specificity was 63%.¹⁰ The sensitivity of the PHQ-A was 50% and the specificity was 98%.¹⁰

Various versions of all of these screening tools can be easily located on the internet. Search for them using the acronyms.

Screening for major depression

The depression screening tests the USPSTF examined were various versions of the Patient Health Questionnaire (PHQ), the Center for Epidemiologic Studies Depression Scale ­(CES-D), the Geriatric Depression Scale (GDS) in older adults, and the EPDS in postpartum and pregnant persons.⁷

A 2-question version of the PHQ was found to have a sensitivity of 91% with a specificity of 67%. The 9-question PHQ was found to have a similar sensitivity (88%) but better specificity (85%).⁷TABLE 3¹¹ lists the 2 questions in the PHQ-2 and explains how to score the results.

Continue to: The most commonly...

The most commonly studied screening tool for adolescents is the PHQ-A. Its sensitivity is 73% and specificity is 94%.¹²

The GAD-2 and PHQ-2 have the same possible answers and scores and can be combined into a 4-question screening tool to assess for anxiety and depression. If an initial screen for anxiety or depression (or both) is positive, further diagnostic testing and follow-up are needed.

Frequency of screening

The USPSTF recognized that limited information on the frequency of screening for both anxiety and depression does not support any recommendation on this matter. It suggested screening everyone once and then basing the need for subsequent screening tests on clinical judgment after considering risk factors and life events, with periodic rescreening of those at high risk. Finally, USPSTF recognized the many challenges to implementing screening tests for mental health conditions in primary care practice, but offered little practical advice on how to do this.

Suicide risk screening

As for the evidence on benefits and harms of screening for suicide risk in all age groups, the USPSTF still regards it as insufficient to make a recommendation. The lack of evidence applies to all aspects of screening, including the accuracy of the various screening tools and the potential benefits and harms of preventive interventions.^2,7

Next steps

The recommendations on screening for depression, suicide risk, and anxiety in adults have been published as a draft, and the public comment period will be over by the time of this publication. The USPSTF generally takes 6 to 9 months to consider all the public comments and to publish final recommendations. The final recommendations on these topics for children and adolescents have been published since drafts were made available last April. There were no major changes between the draft and final versions.

This patient was given a diagnosis of cutaneous mastocytosis. The condition was previously known as urticaria pigmentosa, but in 2016 the World Health Organization reclassified the disease to better suit its pathophysiology as a myeloid cell disorder.¹

As the name suggests, this condition—which involves lesions in a sporadic, truncal distribution—involves overactivation of mastocytes at the tissue level from various stimuli, resulting in histocyte degranulation and hyperpigmentation. The exact cause is unknown. What is known is that it is often associated with other allergic or immunologic conditions and is thought to be related to mutations in the gene for CD-117’s receptor for tyrosine kinase.¹ Incidence is similar to that of asthma, in that it occurs more often in younger patients; a majority of affected individuals will grow out of the disease by adolescence.¹

Although most patients do not experience severe symptomatology, it is still important to differentiate cutaneous vs systemic mastocytosis. If a patient presents with inexplicable systemic symptoms of malaise, vague abdominal pain, heartburn, or flushing, the physician should consider systemic mastocytosis, idiopathic anaphylaxis, or hereditary alpha-tryptasemia.²

The test of choice is a serum tryptase test; levels will be elevated with systemic mastocytosis. Consider obtaining a skin biopsy if lesions are ambiguous or nondistinct.

There is no definitive cure for systemic or cutaneous mastocytosis, so treatment is directed at symptoms. Start by advising patients to avoid triggers and to refrain from scratching the affected areas. Topical antihistamines and oral nonsedating antihistamines can be helpful. If symptoms are more severe, refer the patient to an allergist/immunologist or to a hematologist for further medical management.²

The patient in this case had no systemic symptoms, so she was advised to continue taking oral loratadine 10 mg/d, which had been helpful, and to avoid rubbing her skin.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Murtaza Rizvi, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient was given a diagnosis of cutaneous mastocytosis. The condition was previously known as urticaria pigmentosa, but in 2016 the World Health Organization reclassified the disease to better suit its pathophysiology as a myeloid cell disorder.¹

As the name suggests, this condition—which involves lesions in a sporadic, truncal distribution—involves overactivation of mastocytes at the tissue level from various stimuli, resulting in histocyte degranulation and hyperpigmentation. The exact cause is unknown. What is known is that it is often associated with other allergic or immunologic conditions and is thought to be related to mutations in the gene for CD-117’s receptor for tyrosine kinase.¹ Incidence is similar to that of asthma, in that it occurs more often in younger patients; a majority of affected individuals will grow out of the disease by adolescence.¹

Although most patients do not experience severe symptomatology, it is still important to differentiate cutaneous vs systemic mastocytosis. If a patient presents with inexplicable systemic symptoms of malaise, vague abdominal pain, heartburn, or flushing, the physician should consider systemic mastocytosis, idiopathic anaphylaxis, or hereditary alpha-tryptasemia.²

The test of choice is a serum tryptase test; levels will be elevated with systemic mastocytosis. Consider obtaining a skin biopsy if lesions are ambiguous or nondistinct.

There is no definitive cure for systemic or cutaneous mastocytosis, so treatment is directed at symptoms. Start by advising patients to avoid triggers and to refrain from scratching the affected areas. Topical antihistamines and oral nonsedating antihistamines can be helpful. If symptoms are more severe, refer the patient to an allergist/immunologist or to a hematologist for further medical management.²

The patient in this case had no systemic symptoms, so she was advised to continue taking oral loratadine 10 mg/d, which had been helpful, and to avoid rubbing her skin.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Murtaza Rizvi, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient was given a diagnosis of cutaneous mastocytosis. The condition was previously known as urticaria pigmentosa, but in 2016 the World Health Organization reclassified the disease to better suit its pathophysiology as a myeloid cell disorder.¹

As the name suggests, this condition—which involves lesions in a sporadic, truncal distribution—involves overactivation of mastocytes at the tissue level from various stimuli, resulting in histocyte degranulation and hyperpigmentation. The exact cause is unknown. What is known is that it is often associated with other allergic or immunologic conditions and is thought to be related to mutations in the gene for CD-117’s receptor for tyrosine kinase.¹ Incidence is similar to that of asthma, in that it occurs more often in younger patients; a majority of affected individuals will grow out of the disease by adolescence.¹

Although most patients do not experience severe symptomatology, it is still important to differentiate cutaneous vs systemic mastocytosis. If a patient presents with inexplicable systemic symptoms of malaise, vague abdominal pain, heartburn, or flushing, the physician should consider systemic mastocytosis, idiopathic anaphylaxis, or hereditary alpha-tryptasemia.²

The test of choice is a serum tryptase test; levels will be elevated with systemic mastocytosis. Consider obtaining a skin biopsy if lesions are ambiguous or nondistinct.

There is no definitive cure for systemic or cutaneous mastocytosis, so treatment is directed at symptoms. Start by advising patients to avoid triggers and to refrain from scratching the affected areas. Topical antihistamines and oral nonsedating antihistamines can be helpful. If symptoms are more severe, refer the patient to an allergist/immunologist or to a hematologist for further medical management.²

The patient in this case had no systemic symptoms, so she was advised to continue taking oral loratadine 10 mg/d, which had been helpful, and to avoid rubbing her skin.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Murtaza Rizvi, MD, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in her stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing. The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

It’s recommended that polyps be removed when technically feasible.³ Pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

This patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. A colonoscopy was normal, and the health care team explained that she would require follow-up and surveillance of her condition due to the high risk of future cancers.

‌

This case was adapted from: Warsame MO, McMichael JR. Chronic abdominal pain and diarrhea. J Fam Pract. 2020;69:365,366,368.

Photos courtesy of Mohamed Omar Warsame, MBBS, and Josette R. McMichael, MD

This patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in her stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing. The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

It’s recommended that polyps be removed when technically feasible.³ Pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

This patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. A colonoscopy was normal, and the health care team explained that she would require follow-up and surveillance of her condition due to the high risk of future cancers.

‌

This case was adapted from: Warsame MO, McMichael JR. Chronic abdominal pain and diarrhea. J Fam Pract. 2020;69:365,366,368.

Photos courtesy of Mohamed Omar Warsame, MBBS, and Josette R. McMichael, MD

This patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in her stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing. The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

It’s recommended that polyps be removed when technically feasible.³ Pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

This patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. A colonoscopy was normal, and the health care team explained that she would require follow-up and surveillance of her condition due to the high risk of future cancers.

‌

This case was adapted from: Warsame MO, McMichael JR. Chronic abdominal pain and diarrhea. J Fam Pract. 2020;69:365,366,368.

Photos courtesy of Mohamed Omar Warsame, MBBS, and Josette R. McMichael, MD

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil disease, is a chronic, recurrent, inflammatory occlusive disease affecting the terminal follicular epithelium in apocrine gland–bearing skin areas.¹ HS manifests as painful nodules, abscesses, fistulas, and scarring and often has a severe psychological impact on the affected patient.²

When HS was first identified in the 1800s, it was believed to result from a dysfunction of the sweat glands.³ In 1939, scientists identified the true cause: follicular occlusion.³

Due to its chronic nature, heterogeneity in presentation, and apparent low prevalence,⁴ HS is considered an orphan disease.⁵ Over the past 10 years, there has been a surge in HS research—particularly in medical management—which has provided a better understanding of this condition.^6,7

In this review, we discuss the most updated evidence regarding the diagnosis and treatment of HS to guide the family physician (FP)’s approach to managing this debilitating disease. But first, we offer a word about the etiology and pathophysiology of the condition.

3 events set the stage for hidradenitis suppurativa

Although the exact cause of HS is still unknown, some researchers have hypothesized that HS results from a combination of genetic predisposition and environmental and lifestyle factors.^8-12 The primary mechanism of HS is the obstruction of the terminal follicular epithelium by a keratin plug.^1,13,14 A systematic review of molecular inflammatory pathways involved in HS divides the pathogenesis of HS into 3 events: follicular occlusion followed by dilation, follicular rupture and inflammatory response, and chronic inflammatory state with sinus tracts.⁸

An underreported condition

HS is often underreported and misdiagnosed.^4,15 Globally, the prevalence of HS varies from < 1% to 4%.^15,16 A systematic review with meta-analysis showed a higher prevalence of HS in females compared to males in American and European populations.¹⁷ In the United States, the overall frequency of HS is 0.1%, or 98 per 100,000 persons.¹⁶ The prevalence of HS is highest among patients ages 30 to 39 years; there is decreased prevalence in patients ages 55 years and older.^16,18

Who is at heightened risk?

Recent research has shown a relationship between ethnicity and HS.^16,19,20 African American and biracial groups (defined as African American and White) have a 3-fold and 2-fold greater prevalence of HS, respectively, compared to White patients.¹⁶ However, the prevalence of HS in non-White ethnic groups may be underestimated in clinical trials due to a lack of representation and subgroup analyses based on ethnicity, which may affect generalizability in HS recommendations.²¹

Continue to: Genetic predisposition

Genetic predisposition. As many as 40% of patients with HS report having at least 1 affected family member. A positive family history of HS is associated with earlier onset, longer disease duration, and severe disease.²² HS is genetically heterogeneous, and several mutations (eg, gamma secretase, PSTPIP1, PSEN1 genes) have been identified in patients and in vitro as the cause of dysregulation of epidermal proliferation and differentiation, immune dysregulation, and promotion of amyloid formation.^8,23-25

Obesity and metabolic risk factors. There is a strong relationship between HS and obesity. As many as 70% of patients with HS are obese, and 9% to 40% have metabolic syndrome.^12,18,26-28 Obesity is associated with maceration and mechanical stress, increased fragility of the dermo-epidermal junction, changes in cutaneous blood flow, and subdermal fat inflammation—all of which favor the pathophysiology of HS.^29,30

Smoking. Tobacco smoking is associated with severe HS and a lower chance of remission.¹² Population-based studies have shown that as many as 90% of patients with HS have a history of smoking ≥ 20 packs of cigarettes per year.^{1,12,18,31,32} The nicotine and thousands of other chemicals present in cigarettes trigger keratinocytes and fibroblasts, resulting in epidermal hyperplasia, infundibular hyperkeratosis, excessive cornification, and dysbiosis.^8,23,24

Hormones. The exact role sex hormones play in the pathogenesis of HS remains unclear.^8,32 Most information is based primarily on small studies looking at antiandrogen treatments, HS activity during the menstrual cycle and pregnancy, HS exacerbation related to androgenic effects of hormonal contraception, and the association of HS with metabolic-endocrine disorders (eg, polycystic ovary syndrome [PCOS]).^8,33

A family history of hidradenitis suppurativa is associated with earlier onset, longer disease duration, and severe disease.

Androgens induce hyperkeratosis that may lead to follicular occlusion—the hallmark of HS pathology.³⁴ A systematic review looking at the role of androgen and estrogen in HS found that while some patients with HS have elevated androgen levels, most have androgen and estrogen levels within normal range.³⁵ Therefore, increased peripheral androgen receptor sensitivity has been hypothesized as the mechanism of action contributing to HS manifestation.³⁴

Continue to: Host-defense defects

Host-defense defects. HS shares a similar cytokine profile with other well-­established immune-mediated inflammatory diseases, including pyoderma gangrenosum (PG)^36,37 and Crohn disease.^38-40 HS is characterized by the expression of several immune mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 ­alpha (IL-1 alpha), IL-1 beta, IL-8, IL-17, and the IL-23/T helper 17 pathway, all of which are upregulated in other inflammatory diseases and also result in an abnormal innate immune response.^8,24 The recently described clinical triad of PG, acne, and HS (PASH) and the tetrad of pyogenic arthritis, PG, acne, and HS (PAPASH) further support the role of immune dysregulation in the pathogenesis of HS.⁴⁰ Nonetheless, further studies are needed to determine the exact pathways of cytokine effect in HS.⁴¹

Use these criteria to make the diagnosis

The US and Canadian Hidradenitis Suppurativa Foundations (HSF) guidelines base the clinical diagnosis of HS on the following criteria²:

• Typical HS lesions: Erythematous skin lesions; inflamed, deep-seated painful nodules; “tombstone” double-ended comedones; sinus tracts; scarring; deformity. FIGURES 1A-1E show typical lesions seen in patients with HS.
• Typical locations: Intertriginous regions—apocrine gland–containing areas in axilla, groin, perineal region, buttocks, gluteal cleft, and mammary folds; beltline and waistband areas; areas of skin compression and friction.
• Recurrence and chronicity: Recurrent painful or suppurating lesions that appear more than twice in a 6-month period.^2,41-43

Patients with HS usually present with painful recurrent abscesses and scarring and often report multiple visits to the emergency department for drainage or failed antibiotic treatment for abscesses.^15,44

Ask patients these 2 questions. Vinding et al⁴⁵ developed a survey for the diagnosis of HS using 2 simple questions based on the 3 criteria established by the HSF:

1. “Have you had an outbreak of boils during the last 6 months?” and
2. “Where and how many boils have you had?” (This question includes a list of the typical HS locations—eg, axilla, groin, genitals, area under breast.)

In their questionnaire, Vinding et al⁴⁵ found that an affirmative answer to Question 1 and reports of > 2 boils in response to Question 2 correlated to a sensitivity of 90%, specificity of 97%, positive predictive value of 96%, and negative predictive value of 92% for the diagnosis of HS. The differential diagnosis of HS is summarized in TABLE 1.^42,45-52

Continue to: These tools can help you to stage hidradenitis suppurativa

Multiple tools are available to assess the severity of HS.⁵³ We will describe the Hurley staging system and the International Hidradenitis Suppurativa Severity Score System (IHS4). Other diagnostic tools, such as the Sartorius score and the Hidradenitis Suppurativa Physician’s Global Assessment Scale (HS-PGA), can be time-consuming and challenging to interpret, limiting their use in the clinical setting.^2,54

Hurley staging system (available at www.hsdiseasesource.com/hs-disease-­staging) considers the presence of nodules, abscesses, sinus tracts, and scarring affecting an entire anatomical area.^13,55 This system is most useful as a rapid classification tool for patients with HS in the clinical setting but should not be used to assess clinical response.^2,13,56

The IHS4 (available at https://online­ library.wiley.com/doi/10.1111/bjd.15748) is a validated and easy-to-use tool for assessing HS and guiding the therapeutic strategy in clinical practice.⁵⁴ With IHS4, the clinician must calculate the following:

• total number of nodules > 10 mm in diameter
• total number of abscesses multiplied by 2, and
• total number of draining tunnels (fistulae/sinuses) multiplied by 4.

Mild HS is defined as a score ≤ 3 points; moderate HS, 4 to 10 points; and severe HS, ≥ 11 points.⁵⁴

No diagnostic tests, but ultrasound may be helpful

There are currently no established biological markers or specific tests for diagnosing HS.¹⁵ Ultrasound is emerging as a tool to assess dermal thickness, hair follicle morphology, and number and extent of fluid collections. Two recent studies showed that pairing clinical assessment with ultrasound findings improves accuracy of scoring in 84% of cases.^57,58 For patients with severe HS, skin biopsy can be considered to rule out squamous cell carcinoma. Cultures, however, have limited utility except for suspected superimposed bacterial infection.²

Continue to: Screening for comorbidities

Screening for comorbidities

HSF recommends clinicians screen patients for comorbidities associated with HS (TABLE 2).² Overall, screening patients for active and past history of smoking is strongly recommended, as is screening for metabolic syndrome, hyperlipidemia, type 2 diabetes (1.5- to 3-fold greater risk of type 2 diabetes in HS patients), and PCOS (3-fold greater risk).^2,26,27,59 Screening patients for depression and anxiety is also routinely recommended.² However, the authors of this article strongly recommend screening all patients with HS for psychiatric comorbidities, as research has shown a 2-fold greater risk of depression and anxiety, social isolation, and low self-esteem that severely limits quality of life (QOL) in this patient population.^60,61

Management

Treat existing lesions, reduce formation of new ones

The main goals of treatment for patients with HS are to treat existing lesions and reduce associated symptoms, reduce the formation of new lesions, and minimize associated psychological morbidity.¹⁵ FPs play an important role in the early diagnosis, treatment, and comprehensive care of patients with HS. This includes monitoring patients, managing comorbidities, making appropriate referrals to dermatologists, and coordinating the multidisciplinary care that patients with HS require.

As many as 90% of patients with hidradenitis suppurativa have a history of smoking ≥ 20 packs of cigarettes per year.

A systematic review identified more than 50 interventions used to treat HS, most based on small observational studies and randomized controlled trials (RCTs) with a high risk of bias.⁶² FIGURE 2^2,62-69 provides an evidence-based treatment algorithm for HS, and TABLE 3^{2,63,64,70-75} summarizes the most commonly used treatments.

Biologic agents

Adalimumab (ADA) is a fully human immunoglobulin G1 monoclonal antibody that binds to TNF-alpha, neutralizes its bioactivity, and induces apoptosis of TNF-expressing mononuclear cells. It is the only medication approved by the US Food and Drug Administration for active refractory moderate and severe HS.^62,65 Several double-blinded RCTs, including PIONEER I and PIONEER II, studied the effectiveness of ADA for HS and found significant clinical responses at Week 12, 50% reduction in abscess and nodule counts, no increase in abscesses or draining fistulas at Week 12, and sustained improvement in lesion counts, pain, and QOL.^66,67,76

IL-1 and IL-23 inhibitors. The efficacy of etanercept and golimumab (anti-TNF), as well as anakinra (IL-1 inhibitor) and ustekinumab (IL-1/IL-23 inhibitor), continue to be investigated with variable results; they are considered second-line treatment for active refractory moderate and severe HS after ADA.^65,77-80 In­fliximab (IL-1 beta inhibitor) has shown no effect on reducing disease severity.⁷⁰Compared to other treatments, biologic therapy is associated with higher costs (TABLE 3),^{2,63,64,70-75} an increased risk for reactivation of latent infections (eg, tuberculosis, herpes simplex, and hepatitis C virus [HCV], and B [HBV]), and an attenuated response to vaccines.⁸¹ Prior to starting biologic therapy, FPs should screen patients with HS for tuberculosis and HBV, consider HIV and HCV screening in at-risk patients, and optimize the immunization status of the patient.^82,83 While inactivated vaccines can be administered without discontinuing biologic treatment, patients should avoid live-attenuated vaccines while taking biologics.⁸³

Continue to: Antibiotic therapy

Topical antibiotics are considered first-line treatment for mild and moderate uncomplicated HS.^63,64 Clindamycin 1%, the only topical antibiotic studied in a small double-blind RCT of patients with Hurley stage I and stage II HS, demonstrated significant clinical improvement after 12 weeks of treatment (twice- daily application), compared to placebo.⁸⁴ Topical clindamycin is also recommended to treat flares in patients with mild disease.^2,64

Oral antibiotics. Tetracycline (500 mg twice daily for 4 months) is considered a second-line treatment for patients with mild HS.^64,68 Doxycycline (200 mg/d for 3 months) may also be considered as a second-line treatment in patients with mild disease.⁸⁵

All patients with hidradenitis suppurativa should be screened for depression, anxiety, social isolation, and low self-esteem.

Combination oral clindamycin (300 mg) and rifampicin (300 mg) twice daily for 10 weeks is recommended as first-line treatment for patients with moderate HS.^2,64,69 Combination rifampin (300 mg twice daily), moxifloxacin (400 mg/d), and metronidazole (500 mg three times a day) is not routinely recommended due to increased risk of ­toxicity.²

Ertapenem (1 g intravenously daily for 6 weeks) is supported by lower-level evidence as a third-line rescue therapy option and as a bridge to surgery; however, limitations for home infusions, costs, and concerns for antibiotic resistance limit its use.^2,86

Corticosteroids and systemic immunomodulators

Intralesional triamcinolone (2-20 mg) may be beneficial in the early stages of HS, although its use is based on a small prospective open study of 33 patients.⁸⁷ A recent double-blind placebo-controlled RCT comparing varying concentrations of intralesional triamcinolone (10 mg/mL and 40 mg/mL) vs normal saline showed no statistically significant difference in inflammatory clearance, pain reduction, or patient satisfaction.⁸⁸

Continue to: Short-term systemic corticosteroid tapers...

Short-term systemic corticosteroid tapers (eg, prednisone, starting at 0.5-1 mg/kg) are recommended to treat flares. Long-term corticosteroids and cyclosporine are reserved for patients with severe refractory disease; however, due to safety concerns, their regular use is strongly discouraged.^63,64,85 There is limited evidence to support the use of methotrexate for severe refractory disease, and its use is not recommended.⁶³

Hormonal therapy

The use of hormonal therapy for HS is limited by the low-quality evidence (eg, anecdotal evidence, small retrospective analyses, uncontrolled trials).^33,63 The only exception is a small double-blind controlled crossover trial from 1986 showing that the antiandrogen effects of combination oral contraceptives (ethinyloestradiol 50 mcg/cyproterone acetate in a reverse sequential regimen and ethinyloestradiol 50 mcg/norgestrel 500 mcg) improved HS lesions.⁸⁹

Spironolactone, an antiandrogen diuretic, has been studied in small case report series with a high risk for bias. It is used mainly in female patients with mild or moderate disease, or in combination with other agents in patients with severe HS. Further research is needed to determine its utility in the treatment of HS.^63,90,91

Metformin, alone or in combination with other therapies (dapsone, finasteride, liraglutide), has been analyzed in small prospective studies of primarily female patients with different severities of HS, obesity, and PCOS. These studies have shown improvement in lesions, QOL, and reduction of workdays lost.^92,93

Finasteride. Studies have shown finasteride (1.25-5 mg/d) alone or in combination with other treatments (metformin, liraglutide, levonorgestrel-ethinyl estradiol, and dapsone) provided varying degrees of resolution or improvement in patients with severe and advanced HS. Finasteride has been used for 4 to 16 weeks with a good safety profile.^92,94-96

Continue to: Retinoids

Acitretin, alitretinoin, and isotretinoin have been studied in small retrospective studies to manage HS, with variable results.^97-99 Robust prospective studies are needed. Retinoids, in general, should be considered as a second- or third-line treatment for moderate to severe HS.⁶³

Surgical intervention

Surgical interventions, which should be considered in patients with widespread mild, moderate, or severe disease, are associated with improved daily activity and work productivity.¹⁰⁰ Incision and drainage should be avoided in patients with HS, as this technique does not remove the affected follicles and is associated with 100% recurrence.¹⁰¹

Wide excision is the preferred surgical technique for patients with Hurley stage II and stage III HS; it is associated with lower recurrence rates (13%) compared to local excision (22%) and deroofing (27%).¹⁰² Secondary intention healing is the most commonly chosen method, based on lower recurrence rates than primary closure.¹⁰²

STEEP and laser techniques. The skin-tissue-sparing excision with electrosurgical peeling (STEEP) procedure involves successive tangential excision of affected tissue until the epithelized bottom of the sinus tracts has been reached. This allows for the removal of fibrotic tissue and the sparing of the deep subcutaneous fat. STEEP is associated with 30% of relapses after 43 months.⁷¹

When considering biologic therapy, screen all patients with hidradenitis suppurativa for tuberculosis and hepatitis B, and confirm they are current with age-appropriate immunizations.

Laser surgery has also been studied in patients with Hurley stage II and stage III HS. The most commonly used lasers for HS are the 1064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG) and the carbon dioxide laser; they have been shown to reduce disease severity in inguinal, axillary, and inflammatory sites.^72-74

Pain management: Start with lidocaine, NSAIDs

There are few studies about HS-associated pain management.¹⁰³ For acute episodes, short-acting nonopioid local treatment with lidocaine, topical or oral nonsteroidal anti-inflammatory drugs, and acetaminophen are preferred. Opioids should be reserved for moderate-to-severe pain that has not responded to other analgesics. Adjuvant therapy with pregabalin, gabapentin, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors can also be considered for the comanagement of pain and depression.^62,104

Consider this tool to measure treatment response

The HS clinical response (HiSCR) tool is an outcome measure used to evaluate treatment outcomes. The tool uses an HS-specific binary score with the following criteria:

1. ≥ 50% reduction in the number of inflammatory nodules;
2. no increase in the number of abscesses; and
3. no increase in the number of draining fistulas.¹⁰⁵

The HiSCR was developed for the ­PIONEER studies^105,106 to assess the response to ADA treatment. It is the only HS scoring system to undergo an extensive validation process with a meaningful clinical endpoint for HS treatment evaluation that is easy to use. Compared to the HS-PGA score (clear, minimal, mild), HiSCR was more responsive to change in patients with HS.^105,106 

CORRESPONDENCE
Cristina Marti-Amarista, MD, 101 Nicolls Road, Stony Brook, NY, 11794-8228; [email protected]