Dermatology

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

The FP suspected that the patient had sarcoidosis, based on the infiltrated plaques and their distribution on her face. The appearance of the lesions was similar to images he’d seen online of lupus pernio, a pathognomonic finding of sarcoidosis. The FP recommended a punch biopsy of one of the lesions, and the patient consented.

(See the Watch & Learn video on “Punch biopsy.”)

The FP also sent the patient for a chest x-ray, which showed bilateral hilar adenopathy consistent with sarcoidosis. Histopathology of the biopsy also showed sarcoidosis. Chest radiographic involvement is seen in almost 90% of patients with sarcoidosis and is used in staging the disease. Stage I disease shows bilateral hilar lymphadenopathy (BHL). Stage II disease shows BHL plus pulmonary infiltrates. Stage III disease shows pulmonary infiltrates without BHL. Stage IV disease shows pulmonary fibrosis. In this case, the patient had stage I disease.

The FP prescribed topical 0.1% triamcinolone ointment in an 80 g tube and instructed the patient to apply it to all of the areas involved. Although this medication typically comes in a 15 g or 30 g tube, the FP knew that these quantities would be insufficient. He had also read that a mid-potency steroid would be permissible on the face for this diagnosis. Not having any experience with sarcoidosis, the FP referred the patient to Dermatology and Pulmonology.

The dermatologist started the patient on oral prednisone 40 mg/d and awaited the completion of the patient’s baseline labs before beginning a steroid sparing agent such as methotrexate. Treatments for sarcoidosis include topical steroids, systemic steroids, methotrexate, azathioprine, and biologics (with adalimumab and infliximab having the greatest evidence for effectiveness).

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Bae E, Bae Y, Sarabi K, et al. Sarcoidosis. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1153-1160.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that the patient had sarcoidosis, based on the infiltrated plaques and their distribution on her face. The appearance of the lesions was similar to images he’d seen online of lupus pernio, a pathognomonic finding of sarcoidosis. The FP recommended a punch biopsy of one of the lesions, and the patient consented.

(See the Watch & Learn video on “Punch biopsy.”)

The FP also sent the patient for a chest x-ray, which showed bilateral hilar adenopathy consistent with sarcoidosis. Histopathology of the biopsy also showed sarcoidosis. Chest radiographic involvement is seen in almost 90% of patients with sarcoidosis and is used in staging the disease. Stage I disease shows bilateral hilar lymphadenopathy (BHL). Stage II disease shows BHL plus pulmonary infiltrates. Stage III disease shows pulmonary infiltrates without BHL. Stage IV disease shows pulmonary fibrosis. In this case, the patient had stage I disease.

The FP prescribed topical 0.1% triamcinolone ointment in an 80 g tube and instructed the patient to apply it to all of the areas involved. Although this medication typically comes in a 15 g or 30 g tube, the FP knew that these quantities would be insufficient. He had also read that a mid-potency steroid would be permissible on the face for this diagnosis. Not having any experience with sarcoidosis, the FP referred the patient to Dermatology and Pulmonology.

The dermatologist started the patient on oral prednisone 40 mg/d and awaited the completion of the patient’s baseline labs before beginning a steroid sparing agent such as methotrexate. Treatments for sarcoidosis include topical steroids, systemic steroids, methotrexate, azathioprine, and biologics (with adalimumab and infliximab having the greatest evidence for effectiveness).

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Bae E, Bae Y, Sarabi K, et al. Sarcoidosis. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1153-1160.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that the patient had sarcoidosis, based on the infiltrated plaques and their distribution on her face. The appearance of the lesions was similar to images he’d seen online of lupus pernio, a pathognomonic finding of sarcoidosis. The FP recommended a punch biopsy of one of the lesions, and the patient consented.

(See the Watch & Learn video on “Punch biopsy.”)

The FP also sent the patient for a chest x-ray, which showed bilateral hilar adenopathy consistent with sarcoidosis. Histopathology of the biopsy also showed sarcoidosis. Chest radiographic involvement is seen in almost 90% of patients with sarcoidosis and is used in staging the disease. Stage I disease shows bilateral hilar lymphadenopathy (BHL). Stage II disease shows BHL plus pulmonary infiltrates. Stage III disease shows pulmonary infiltrates without BHL. Stage IV disease shows pulmonary fibrosis. In this case, the patient had stage I disease.

The FP prescribed topical 0.1% triamcinolone ointment in an 80 g tube and instructed the patient to apply it to all of the areas involved. Although this medication typically comes in a 15 g or 30 g tube, the FP knew that these quantities would be insufficient. He had also read that a mid-potency steroid would be permissible on the face for this diagnosis. Not having any experience with sarcoidosis, the FP referred the patient to Dermatology and Pulmonology.

The dermatologist started the patient on oral prednisone 40 mg/d and awaited the completion of the patient’s baseline labs before beginning a steroid sparing agent such as methotrexate. Treatments for sarcoidosis include topical steroids, systemic steroids, methotrexate, azathioprine, and biologics (with adalimumab and infliximab having the greatest evidence for effectiveness).

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Bae E, Bae Y, Sarabi K, et al. Sarcoidosis. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1153-1160.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

An 8-year-old boy is brought in for evaluation of a collection of blisters on his finger, near the nail. The problem manifested about 6 days ago. The affected area is tender to touch. The child reportedly feels well, with no fever or malaise.

The patient has an extensive personal and family history of atopy. Since birth, he has had dry, sensitive skin and has experienced episodes of eczema, seasonal allergies, and asthma. Three months ago, he was admitted to the hospital with eczema herpeticum and successfully treated with IV acyclovir.

EXAMINATION
A cluster of vesicles is seen in the lateral perionychial area of the left third finger. Very modest erythema surrounds the vesicles, which contain cloudy yellow fluid suggestive of pus. There is a palpable lymph node in the left epitrochlear area.

The child is afebrile and in no distress. Patches of mild eczema are seen on the extremities and trunk.

What’s the diagnosis?

DISCUSSION
The lesion on this child’s finger is a herpetic whitlow. Patients with atopy are often susceptible to all types of skin infections: bacterial, fungal, and viral. In fact, human papillomavirus infection manifesting as multiple warts is not uncommon in this population. Nor is herpes simplex virus (HSV) infection, of which this case represents 1 manifestation.

A culture could have been done to confirm the diagnosis, but that would entail opening a vesicle to collect the fluid and then waiting at least 2 weeks for the results. By then, this whitlow would have long since resolved.

As with all HSV infections in the immunocompetent, treatment with acyclovir must be started in the first 2 to 3 days to have any effect—so such treatment in this case would be useless. If the herpetic whitlow were to recur in the same location, prompt treatment could be initiated, which would likely shorten the disease course and reduce symptoms.

Another HSV infection seen almost exclusively in atopic patients is eczema herpeticum (also known as Kaposi varicelliform eruption). This diffuse infection comprises dozens of tiny papulovesicular lesions, mostly concentrated on the face but often spilling down onto the chest. Patients with Darier disease or seborrheic dermatitis can also acquire it.

TAKE-HOME LEARNING POINTS

• Patients with atopy, especially children, are susceptible to all kinds of skin infections—fungal, bacterial, and viral.
• Herpes simplex virus (HSV) can appear in almost any location, including on fingers, but can also manifest as diffuse papulovesicular lesions on the face and chest of atopic patients.
• The blisters/vesicles of HSV are often pus-filled and usually provoke regional adenopathy.
• If diagnosed early enough, herpetic whitlows can be successfully treated with oral acyclovir; this doesn’t provide a cure but does stop the particular episode.

An 8-year-old boy is brought in for evaluation of a collection of blisters on his finger, near the nail. The problem manifested about 6 days ago. The affected area is tender to touch. The child reportedly feels well, with no fever or malaise.

The patient has an extensive personal and family history of atopy. Since birth, he has had dry, sensitive skin and has experienced episodes of eczema, seasonal allergies, and asthma. Three months ago, he was admitted to the hospital with eczema herpeticum and successfully treated with IV acyclovir.

EXAMINATION
A cluster of vesicles is seen in the lateral perionychial area of the left third finger. Very modest erythema surrounds the vesicles, which contain cloudy yellow fluid suggestive of pus. There is a palpable lymph node in the left epitrochlear area.

The child is afebrile and in no distress. Patches of mild eczema are seen on the extremities and trunk.

What’s the diagnosis?

DISCUSSION
The lesion on this child’s finger is a herpetic whitlow. Patients with atopy are often susceptible to all types of skin infections: bacterial, fungal, and viral. In fact, human papillomavirus infection manifesting as multiple warts is not uncommon in this population. Nor is herpes simplex virus (HSV) infection, of which this case represents 1 manifestation.

A culture could have been done to confirm the diagnosis, but that would entail opening a vesicle to collect the fluid and then waiting at least 2 weeks for the results. By then, this whitlow would have long since resolved.

As with all HSV infections in the immunocompetent, treatment with acyclovir must be started in the first 2 to 3 days to have any effect—so such treatment in this case would be useless. If the herpetic whitlow were to recur in the same location, prompt treatment could be initiated, which would likely shorten the disease course and reduce symptoms.

Another HSV infection seen almost exclusively in atopic patients is eczema herpeticum (also known as Kaposi varicelliform eruption). This diffuse infection comprises dozens of tiny papulovesicular lesions, mostly concentrated on the face but often spilling down onto the chest. Patients with Darier disease or seborrheic dermatitis can also acquire it.

TAKE-HOME LEARNING POINTS

• Patients with atopy, especially children, are susceptible to all kinds of skin infections—fungal, bacterial, and viral.
• Herpes simplex virus (HSV) can appear in almost any location, including on fingers, but can also manifest as diffuse papulovesicular lesions on the face and chest of atopic patients.
• The blisters/vesicles of HSV are often pus-filled and usually provoke regional adenopathy.
• If diagnosed early enough, herpetic whitlows can be successfully treated with oral acyclovir; this doesn’t provide a cure but does stop the particular episode.

An 8-year-old boy is brought in for evaluation of a collection of blisters on his finger, near the nail. The problem manifested about 6 days ago. The affected area is tender to touch. The child reportedly feels well, with no fever or malaise.

The patient has an extensive personal and family history of atopy. Since birth, he has had dry, sensitive skin and has experienced episodes of eczema, seasonal allergies, and asthma. Three months ago, he was admitted to the hospital with eczema herpeticum and successfully treated with IV acyclovir.

EXAMINATION
A cluster of vesicles is seen in the lateral perionychial area of the left third finger. Very modest erythema surrounds the vesicles, which contain cloudy yellow fluid suggestive of pus. There is a palpable lymph node in the left epitrochlear area.

The child is afebrile and in no distress. Patches of mild eczema are seen on the extremities and trunk.

What’s the diagnosis?

DISCUSSION
The lesion on this child’s finger is a herpetic whitlow. Patients with atopy are often susceptible to all types of skin infections: bacterial, fungal, and viral. In fact, human papillomavirus infection manifesting as multiple warts is not uncommon in this population. Nor is herpes simplex virus (HSV) infection, of which this case represents 1 manifestation.

A culture could have been done to confirm the diagnosis, but that would entail opening a vesicle to collect the fluid and then waiting at least 2 weeks for the results. By then, this whitlow would have long since resolved.

As with all HSV infections in the immunocompetent, treatment with acyclovir must be started in the first 2 to 3 days to have any effect—so such treatment in this case would be useless. If the herpetic whitlow were to recur in the same location, prompt treatment could be initiated, which would likely shorten the disease course and reduce symptoms.

Another HSV infection seen almost exclusively in atopic patients is eczema herpeticum (also known as Kaposi varicelliform eruption). This diffuse infection comprises dozens of tiny papulovesicular lesions, mostly concentrated on the face but often spilling down onto the chest. Patients with Darier disease or seborrheic dermatitis can also acquire it.

TAKE-HOME LEARNING POINTS

• Patients with atopy, especially children, are susceptible to all kinds of skin infections—fungal, bacterial, and viral.
• Herpes simplex virus (HSV) can appear in almost any location, including on fingers, but can also manifest as diffuse papulovesicular lesions on the face and chest of atopic patients.
• The blisters/vesicles of HSV are often pus-filled and usually provoke regional adenopathy.
• If diagnosed early enough, herpetic whitlows can be successfully treated with oral acyclovir; this doesn’t provide a cure but does stop the particular episode.

See Mangione and Aronowitz editorials

Mechanical pressure induced by friction of the elbows on the thighs may result in proliferation of the stratum corneum and the release of hemosiderin from erythrocytes, resulting in the skin changes seen in this patient, which because of the tripod positioning are known as “thinker’s sign,” a term coined in 1963 by Rothenberg¹ to describe findings in patients with chronic pulmonary disease and advanced respiratory insufficiency. It is also referred to as the Dahl sign, based on a report by Dahl of similar findings in patients with emphysema.²

See Mangione and Aronowitz editorials

Mechanical pressure induced by friction of the elbows on the thighs may result in proliferation of the stratum corneum and the release of hemosiderin from erythrocytes, resulting in the skin changes seen in this patient, which because of the tripod positioning are known as “thinker’s sign,” a term coined in 1963 by Rothenberg¹ to describe findings in patients with chronic pulmonary disease and advanced respiratory insufficiency. It is also referred to as the Dahl sign, based on a report by Dahl of similar findings in patients with emphysema.²

See Mangione and Aronowitz editorials

Mechanical pressure induced by friction of the elbows on the thighs may result in proliferation of the stratum corneum and the release of hemosiderin from erythrocytes, resulting in the skin changes seen in this patient, which because of the tripod positioning are known as “thinker’s sign,” a term coined in 1963 by Rothenberg¹ to describe findings in patients with chronic pulmonary disease and advanced respiratory insufficiency. It is also referred to as the Dahl sign, based on a report by Dahl of similar findings in patients with emphysema.²

MILAN – A cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.

Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.

Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.

“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.

Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.

The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.


After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.

The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.

In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.

The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.

The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.

Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.

Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.

Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.

The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.

Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.

The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.

Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.

MILAN – A cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.

Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.

Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.

“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.

Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.

The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.


After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.

The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.

In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.

The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.

The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.

Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.

Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.

Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.

The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.

Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.

The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.

Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.

MILAN – A cream-based formulation of the Janus kinase (JAK) inhibitor ruxolitinib maintained its efficacy in the 4-week open-label period of a 16-week randomized phase 2 study of adults with mild to moderate atopic dermatitis (AD), Leon H. Kircik, MD, said at the World Congress of Dermatology.

Improvements in disease severity and itch in patients receiving 1.5% ruxolitinib cream twice daily were sustained over the open-label period, said Dr. Kircik, a dermatologist in Louisville, Ky., affiliated with Mount Sinai Medical Center, New York.

Patients who switched from vehicle or 0.1% triamcinolone cream to the JAK1/2 selective inhibitor in the open-label period also experienced rapid improvements in disease severity and itch.

“This is a novel treatment that’s a topical JAK inhibitor, which so far we don’t have any in the market for atopic dermatitis, and it does have a very good efficacy and safety profile,” Dr. Kircik said during an oral presentation at the meeting.

Janus kinases modulate inflammatory cytokines implicated in AD, and may also directly modulate itch, Dr. Kircik noted.

The study comprised 307 adults with mild to moderate AD (Investigator’s Global Assessment [IGA] score of 2 or 3) and body surface area involvement of 3%-20%. They were randomized equally to six arms, including vehicle, triamcinolone cream, and ruxolitinib at dosages of 0.15%, 0.5%, 1.5% once daily, or the target dose level of 1.5% twice daily.


After an 8-week double-blind period, there was a 4-week open-label period during which patients randomized to vehicle or triamcinolone were switched to ruxolitinib, and then a 4-week follow-up period during which no treatment was given, Dr. Kircik said.

The mean age of the patients was 35 years, 54% were female, and the median duration of disease was 20.8 years.

In the double-blind period, 1.5% ruxolitinib cream twice daily significantly improved Eczema Area and Severity Index (EASI) score versus vehicle, Dr. Kircik said.

The mean change in EASI scores at weeks 2, 4, and 6 were 52.7%, 71.6%, and 78.5% for ruxolitinib, versus 4.8%, 15.5%, and 26.9% for vehicle (P less than .001 for all comparisons), according to Dr. Kircik.

The patients on the target ruxolitinib dose maintained the improvements in EASI score throughout the open label period, with mean improvement from baseline reaching 81.4% by week 10 and 84.9% by week 12.

Meanwhile, there was a sharp increase in mean EASI score improvement in patients switched to ruxolitinib, according to Dr. Kircik. In the vehicle arm, mean improvement leapt from 26.9% at week 8 to 78.4% by week 12.

Significant reductions in itch scores were seen within 36 hours of starting the 1.5% ruxolitinib cream, with itch Numeric Rating Scale (NRS) scores of –1.8 versus –0.2 for vehicle at that time point (P less than .0001), he added.

Reduction in itch score was similarly maintained in the ruxolitinib target dose group, and rapidly fell to similar levels for patients switched over to that treatment in the open-label period, Dr. Kircik said.

The target ruxolitinib dose was also noninferior to triamcinolone cream, for which mean change in EASI scores at weeks 2 and 4 were 40.0% and 59.8%, respectively.

Recruitment of patients in phase 3 studies of ruxolitinib cream for AD has just started, Dr. Kircik said.

The TRuE AD1 and TRuE AD2 studies are set to enroll 1,200 adolescents and adults with AD who will be randomized to ruxolitinib cream or vehicle, according to listings on ClinicalTrials.gov.

Dr. Kircik disclosed ties to several companies including Incyte, which was the sponsor of the phase 2 study and the phase 3 studies.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

MILAN – Upadacitinib significantly improved itch in a recent randomized, placebo-controlled trial enrolling patients with moderate to severe atopic dermatitis, according to a report presented at the World Congress of Dermatology.

Compared with those in the placebo group, more patients receiving the selective Janus kinase 1 (JAK1) inhibitor achieved an itch-free state and maintained it over the 16 weeks of the phase 2b trial, said investigator Kristian Reich, MD, professor of translational research in inflammatory skin diseases at the University Medical Center Hamburg-Eppendorf (Germany).

These improvements in pruritus occurred early with upadacitinib and were pronounced at the highest dose studied, 30 mg daily, he commented. Treatment with upadacitinib also rapidly and significantly improved clinical signs of AD versus placebo, as previously reported primary endpoint data show.

“It’s a drug that works in eczema,” Dr. Reich said in an oral presentation. “We still do not fully understand what the exact relationship between itch and eczema is. Is there a neurogenic inflammation? Is there an epidermal pathology? But clearly with this drug, it does seem to reduce the itch, it does reduce the eczema, it does this early on, and the 30 mg does seem to be the right dose.”

Upadacitinib is a selective inhibitor of JAK1, a member of the signal transduction cascade for many cytokines implicated in AD, including interleukin-4, IL-13, IL-22, and others, Dr. Reich told attendees at the meeting.


In the phase 2b study, 167 patients with moderate to severe AD were randomized to placebo or upadacitinib at 7.5 mg, 15 mg, or 30 mg daily over a 16-week, double-blind period, followed by a 72-week, blinded extension. The mean age across these groups ranged from 39 to 42 years, and the mean time since onset of symptoms was 24-34 years.

Significantly improvements in Eczema Area and Severity Index (EASI) scores were seen as early as 2 weeks and were maintained throughout the 16-week, double-blind period, as previously shown. By 16 weeks, the mean percentage improvement in EASI score was 74.4% for upadacitinib 30 mg daily versus 23.0% for placebo (P less than .001).

In this more recent post hoc analysis of itch, the percentage of patients with a weekly rolling average pruritus Numerical Rating Scale (NRS) score of 0-1 was significantly higher in the upadacitinib groups, Dr. Reich said.

The placebo-adjusted difference in average pruritus NRS scores of 0-1 was highest in the 30-mg daily group, at 37.7% by week 16 (P less than .001).

Those itch scores correlated with the Patient Global Impression of Severity results, in that almost all patients rating their disease as absent or minimal by that scale also had a pruritus NRS score of 0 (81.6%) or 1 (10.5%), he said.

That link shows the important contribution of itch to the overall rating of disease severity by the patient. “Patients want to be able to say, ‘I have only minimal or absent disease,’ ” he said. “This will likely require that you really get the itch down, for example, to 0 or 1, using this pruritus numerical rating scale.”

Pruritus improvements in favor of upadacitinib were also seen when using Scoring AD itch and Patient-Oriented Eczema Measure (POEM) itch measures, Dr. Reich said. With POEM, 0% of placebo-treated patients had 0 days of itch in the past week, compared with 28.6% in the upadacitinib 30-mg daily group.

The risk-to-benefit profile of upadacitinib supports proceeding to phase 3 trials in patients with AD, according to Dr. Reich and coinvestigators.

Phase 3 trials of upadacitinib are underway in AD, psoriatic arthritis, Crohn’s disease, and ulcerative colitis, according to a recent AbbVie press release. The Food and Drug Administration accepted a New Drug Application Accepted For Priority Review for upadacitinib treatment of moderate to severe RA, based on a phase 3 program including more than 4,900 patients, the company announced in February.

Support for the study was provided by AbbVie. Dr. Reich reported disclosures related to AbbVie, Affibody, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Eli Lilly, Medac Pharma, Merck, Novartis, Pfizer, Regeneron, Takeda, UCB, and XenoPort.

The FP noted that a pattern seemed to start on the patient’s second finger and spread up his arm. He considered that this skin disease might be secondary to sporotrichosis (a deep fungal infection, also referred to as rose gardener’s disease).

Sporotrichosis typically spreads up the arm from an inoculation of the hand from a scratch of a rose thorn. The ulcers partially resemble pyoderma gangrenosum, but the edges are neither undermined nor the color of gun metal. While sporotrichosis may be spread to humans through injuries while working with rose bushes, many other plants and animals can carry the organism Sporothrix schenckii.

The FP decided to offer a definitive diagnosis with a fungal culture since sporotrichosis treatment would require months of an oral antifungal agent. Obtaining a fungal culture would require a punch biopsy because the Sporothrix schenckii grows deeply in the tissue and is not reliably found on the skin surface. The mother and patient consented to the procedure and the FP performed a 4-mm punch biopsy on the edge of the largest ulcer on the arm. The specimen was placed in a sterile urine culture cup on sterile gauze with some saline (preservative free). (See the Watch & Learn video on “Punch biopsy.”)

It is important to note that that if the specimen had been sent in standard formalin, a culture could not be performed and histology could miss the dead organism. Clinical suspicion for sporotrichosis was so high in this case that the FP prescribed oral itraconazole 200 mg daily for the next 2 weeks while awaiting the fungal culture result.

The fungal culture grew out Sporothrix schenckii. The FP prescribed itraconazole 200 mg daily for 3 months and planned to continue the therapy until at least 2 to 4 weeks after the lesions had healed. With monthly follow-up visits, the itraconazole treatment lasted 5 months.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP noted that a pattern seemed to start on the patient’s second finger and spread up his arm. He considered that this skin disease might be secondary to sporotrichosis (a deep fungal infection, also referred to as rose gardener’s disease).

Sporotrichosis typically spreads up the arm from an inoculation of the hand from a scratch of a rose thorn. The ulcers partially resemble pyoderma gangrenosum, but the edges are neither undermined nor the color of gun metal. While sporotrichosis may be spread to humans through injuries while working with rose bushes, many other plants and animals can carry the organism Sporothrix schenckii.

The FP decided to offer a definitive diagnosis with a fungal culture since sporotrichosis treatment would require months of an oral antifungal agent. Obtaining a fungal culture would require a punch biopsy because the Sporothrix schenckii grows deeply in the tissue and is not reliably found on the skin surface. The mother and patient consented to the procedure and the FP performed a 4-mm punch biopsy on the edge of the largest ulcer on the arm. The specimen was placed in a sterile urine culture cup on sterile gauze with some saline (preservative free). (See the Watch & Learn video on “Punch biopsy.”)

It is important to note that that if the specimen had been sent in standard formalin, a culture could not be performed and histology could miss the dead organism. Clinical suspicion for sporotrichosis was so high in this case that the FP prescribed oral itraconazole 200 mg daily for the next 2 weeks while awaiting the fungal culture result.

The fungal culture grew out Sporothrix schenckii. The FP prescribed itraconazole 200 mg daily for 3 months and planned to continue the therapy until at least 2 to 4 weeks after the lesions had healed. With monthly follow-up visits, the itraconazole treatment lasted 5 months.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP noted that a pattern seemed to start on the patient’s second finger and spread up his arm. He considered that this skin disease might be secondary to sporotrichosis (a deep fungal infection, also referred to as rose gardener’s disease).

Sporotrichosis typically spreads up the arm from an inoculation of the hand from a scratch of a rose thorn. The ulcers partially resemble pyoderma gangrenosum, but the edges are neither undermined nor the color of gun metal. While sporotrichosis may be spread to humans through injuries while working with rose bushes, many other plants and animals can carry the organism Sporothrix schenckii.

The FP decided to offer a definitive diagnosis with a fungal culture since sporotrichosis treatment would require months of an oral antifungal agent. Obtaining a fungal culture would require a punch biopsy because the Sporothrix schenckii grows deeply in the tissue and is not reliably found on the skin surface. The mother and patient consented to the procedure and the FP performed a 4-mm punch biopsy on the edge of the largest ulcer on the arm. The specimen was placed in a sterile urine culture cup on sterile gauze with some saline (preservative free). (See the Watch & Learn video on “Punch biopsy.”)

It is important to note that that if the specimen had been sent in standard formalin, a culture could not be performed and histology could miss the dead organism. Clinical suspicion for sporotrichosis was so high in this case that the FP prescribed oral itraconazole 200 mg daily for the next 2 weeks while awaiting the fungal culture result.

The fungal culture grew out Sporothrix schenckii. The FP prescribed itraconazole 200 mg daily for 3 months and planned to continue the therapy until at least 2 to 4 weeks after the lesions had healed. With monthly follow-up visits, the itraconazole treatment lasted 5 months.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

This woman, now 44, first developed subcutaneous “bumps” on her neck, arms, and chest at puberty. They were initially diagnosed as acne, but treatment for that condition failed to help.

Later, she consulted a dermatologist, who suggested they were cysts and actually removed one to send for pathologic examination. The report indicated “a type of cyst,” the name of which the patient has long since forgotten.

Over the years, she has developed additional lesions, which are not only unsightly but also painful at times. Although the patient is not in distress, she is upset.

The patient has type IV skin and is of African-American ancestry. Further history-taking reveals that she is reasonably healthy, with no other skin problems. She does report that the presenting complaint “runs in the family,” on her father’s side.

EXAMINATION
The lesions—subcutaneous, doughy, cystic-feeling papules and nodules—are widely distributed on the patient’s anterior neck, arms, and chest. They range in size from 5 mm to 3 cm. None are inflamed, and no puncta can be seen on their surfaces. Palpation provokes no reaction of pain or discomfort.

With the patient’s permission, she is anesthetized and one lesion is removed. The sample clearly establishes a cystic nature, although the contents are neither cheesy nor grumous as would be seen with an ordinary epidermal cyst. Rather, they are an oily, odorless, thick liquid surrounded by an organized cyst wall. This is removed as well and sent for pathologic examination.

What’s the diagnosis?

DISCUSSION
The pathology report confirmed the lesions to be steatocystoma—in this case, part of an autosomal dominantly inherited condition called steatocystoma multiplex (SM). When these manifest as solitary lesions, they are known as steatocystoma simplex—a true sebaceous cyst, quite different from the common epidermal cyst that contains cheesy, odoriferous material and is frequently misnamed “sebaceous cyst.”

Steatocystoma can develop spontaneously, without any genetic predisposition. SM, however, is quite unusual (if not rare) and results from a defect in keratin 17 that allows the accumulation of sebum at the base of the follicle. It has no other pathologic implication.

However, in a case such as this, SM presents a real problem, because the only effective treatment is complete excision. This not only leaves a scar, but also, in those with skin of color, has the potential to produce hypertrophic scarring or even keloid formation. Worse, in many cases, the patient keeps developing cysts in new locations.

TAKE-HOME LEARNING POINTS

• Steatocystoma multiplex (SM) is an autosomal dominant condition in which the patient, usually at puberty, develops sebum-filled cysts.
• These cysts can occur as solitary lesions (steatocystoma simplex) but more often manifest in multiples on the neck, face, chest, and arms.
• SM cysts are full of clear or yellowish sebum, unlike common epidermal cysts, which are filled with cheesy, often odoriferous material.
• The only effective treatment for SM cysts is complete excision.

This woman, now 44, first developed subcutaneous “bumps” on her neck, arms, and chest at puberty. They were initially diagnosed as acne, but treatment for that condition failed to help.

Later, she consulted a dermatologist, who suggested they were cysts and actually removed one to send for pathologic examination. The report indicated “a type of cyst,” the name of which the patient has long since forgotten.

Over the years, she has developed additional lesions, which are not only unsightly but also painful at times. Although the patient is not in distress, she is upset.

The patient has type IV skin and is of African-American ancestry. Further history-taking reveals that she is reasonably healthy, with no other skin problems. She does report that the presenting complaint “runs in the family,” on her father’s side.

EXAMINATION
The lesions—subcutaneous, doughy, cystic-feeling papules and nodules—are widely distributed on the patient’s anterior neck, arms, and chest. They range in size from 5 mm to 3 cm. None are inflamed, and no puncta can be seen on their surfaces. Palpation provokes no reaction of pain or discomfort.

With the patient’s permission, she is anesthetized and one lesion is removed. The sample clearly establishes a cystic nature, although the contents are neither cheesy nor grumous as would be seen with an ordinary epidermal cyst. Rather, they are an oily, odorless, thick liquid surrounded by an organized cyst wall. This is removed as well and sent for pathologic examination.

What’s the diagnosis?

DISCUSSION
The pathology report confirmed the lesions to be steatocystoma—in this case, part of an autosomal dominantly inherited condition called steatocystoma multiplex (SM). When these manifest as solitary lesions, they are known as steatocystoma simplex—a true sebaceous cyst, quite different from the common epidermal cyst that contains cheesy, odoriferous material and is frequently misnamed “sebaceous cyst.”

Steatocystoma can develop spontaneously, without any genetic predisposition. SM, however, is quite unusual (if not rare) and results from a defect in keratin 17 that allows the accumulation of sebum at the base of the follicle. It has no other pathologic implication.

However, in a case such as this, SM presents a real problem, because the only effective treatment is complete excision. This not only leaves a scar, but also, in those with skin of color, has the potential to produce hypertrophic scarring or even keloid formation. Worse, in many cases, the patient keeps developing cysts in new locations.

TAKE-HOME LEARNING POINTS

• Steatocystoma multiplex (SM) is an autosomal dominant condition in which the patient, usually at puberty, develops sebum-filled cysts.
• These cysts can occur as solitary lesions (steatocystoma simplex) but more often manifest in multiples on the neck, face, chest, and arms.
• SM cysts are full of clear or yellowish sebum, unlike common epidermal cysts, which are filled with cheesy, often odoriferous material.
• The only effective treatment for SM cysts is complete excision.

This woman, now 44, first developed subcutaneous “bumps” on her neck, arms, and chest at puberty. They were initially diagnosed as acne, but treatment for that condition failed to help.

Later, she consulted a dermatologist, who suggested they were cysts and actually removed one to send for pathologic examination. The report indicated “a type of cyst,” the name of which the patient has long since forgotten.

Over the years, she has developed additional lesions, which are not only unsightly but also painful at times. Although the patient is not in distress, she is upset.

The patient has type IV skin and is of African-American ancestry. Further history-taking reveals that she is reasonably healthy, with no other skin problems. She does report that the presenting complaint “runs in the family,” on her father’s side.

EXAMINATION
The lesions—subcutaneous, doughy, cystic-feeling papules and nodules—are widely distributed on the patient’s anterior neck, arms, and chest. They range in size from 5 mm to 3 cm. None are inflamed, and no puncta can be seen on their surfaces. Palpation provokes no reaction of pain or discomfort.

With the patient’s permission, she is anesthetized and one lesion is removed. The sample clearly establishes a cystic nature, although the contents are neither cheesy nor grumous as would be seen with an ordinary epidermal cyst. Rather, they are an oily, odorless, thick liquid surrounded by an organized cyst wall. This is removed as well and sent for pathologic examination.

What’s the diagnosis?

DISCUSSION
The pathology report confirmed the lesions to be steatocystoma—in this case, part of an autosomal dominantly inherited condition called steatocystoma multiplex (SM). When these manifest as solitary lesions, they are known as steatocystoma simplex—a true sebaceous cyst, quite different from the common epidermal cyst that contains cheesy, odoriferous material and is frequently misnamed “sebaceous cyst.”

Steatocystoma can develop spontaneously, without any genetic predisposition. SM, however, is quite unusual (if not rare) and results from a defect in keratin 17 that allows the accumulation of sebum at the base of the follicle. It has no other pathologic implication.

However, in a case such as this, SM presents a real problem, because the only effective treatment is complete excision. This not only leaves a scar, but also, in those with skin of color, has the potential to produce hypertrophic scarring or even keloid formation. Worse, in many cases, the patient keeps developing cysts in new locations.

TAKE-HOME LEARNING POINTS

• Steatocystoma multiplex (SM) is an autosomal dominant condition in which the patient, usually at puberty, develops sebum-filled cysts.
• These cysts can occur as solitary lesions (steatocystoma simplex) but more often manifest in multiples on the neck, face, chest, and arms.
• SM cysts are full of clear or yellowish sebum, unlike common epidermal cysts, which are filled with cheesy, often odoriferous material.
• The only effective treatment for SM cysts is complete excision.

The FP noted the deep ulcers with gun-metal (violet blue coloration) undermined borders. The edge of the upper left corner of the suprapubic ulcer also had a cribriform pattern (pierced with holes like swiss cheese). The FP’s differential diagnosis included pyoderma gangrenosum (PG) and a deep fungal infection.

The FP was aware that it could take months before the patient could be seen be a dermatologist, so he offered to perform a 4-mm punch biopsy at the edge of the ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). (See the Watch & Learn video on “Punch biopsy.”)

The pathologist found a dense neutrophilic infiltrate and stated that this supported the diagnosis of PG. No fungal elements were seen with a Periodic acid–Schiff (PAS) stain. PG is a rare neutrophilic dermatosis, without a known cause, that is sometimes seen with inflammatory bowel disease.

The FP called a local dermatologist, and they decided to start the patient on oral prednisone until she could be seen in the dermatologist’s office. The dermatologist stated that she would be considering oral cyclosporine, oral dapsone, or injectable biologic agents as steroid sparing agents to treat the PG.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP noted the deep ulcers with gun-metal (violet blue coloration) undermined borders. The edge of the upper left corner of the suprapubic ulcer also had a cribriform pattern (pierced with holes like swiss cheese). The FP’s differential diagnosis included pyoderma gangrenosum (PG) and a deep fungal infection.

The FP was aware that it could take months before the patient could be seen be a dermatologist, so he offered to perform a 4-mm punch biopsy at the edge of the ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). (See the Watch & Learn video on “Punch biopsy.”)

The pathologist found a dense neutrophilic infiltrate and stated that this supported the diagnosis of PG. No fungal elements were seen with a Periodic acid–Schiff (PAS) stain. PG is a rare neutrophilic dermatosis, without a known cause, that is sometimes seen with inflammatory bowel disease.

The FP called a local dermatologist, and they decided to start the patient on oral prednisone until she could be seen in the dermatologist’s office. The dermatologist stated that she would be considering oral cyclosporine, oral dapsone, or injectable biologic agents as steroid sparing agents to treat the PG.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP noted the deep ulcers with gun-metal (violet blue coloration) undermined borders. The edge of the upper left corner of the suprapubic ulcer also had a cribriform pattern (pierced with holes like swiss cheese). The FP’s differential diagnosis included pyoderma gangrenosum (PG) and a deep fungal infection.

The FP was aware that it could take months before the patient could be seen be a dermatologist, so he offered to perform a 4-mm punch biopsy at the edge of the ulcer. (Note that the correct location for a biopsy of an ulcer is on the edge, not in the middle). (See the Watch & Learn video on “Punch biopsy.”)

The pathologist found a dense neutrophilic infiltrate and stated that this supported the diagnosis of PG. No fungal elements were seen with a Periodic acid–Schiff (PAS) stain. PG is a rare neutrophilic dermatosis, without a known cause, that is sometimes seen with inflammatory bowel disease.

The FP called a local dermatologist, and they decided to start the patient on oral prednisone until she could be seen in the dermatologist’s office. The dermatologist stated that she would be considering oral cyclosporine, oral dapsone, or injectable biologic agents as steroid sparing agents to treat the PG.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd Ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.

Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.¹ Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.² BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.³ Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.

Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.

The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.

He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.⁴

Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.⁵ Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.⁶

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.

2. Eur J Med Genet. 2015;58(5):271-8.

3. Am J Dermatopathol. 2014;36(11):868-74.

4. Int J Dermatol. 2016 Apr;55(4):367-75.

5. Int J Dermatol. 2007;46(6):583-6.

6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.

A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.

Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.¹ Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.² BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.³ Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.

Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.

The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.

He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.⁴

Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.⁵ Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.⁶

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.

2. Eur J Med Genet. 2015;58(5):271-8.

3. Am J Dermatopathol. 2014;36(11):868-74.

4. Int J Dermatol. 2016 Apr;55(4):367-75.

5. Int J Dermatol. 2007;46(6):583-6.

6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.

A shave biopsy of one of the lesions was performed that showed a proliferation of nests of basaloid cells on the dermis with palisading and rare vacuolated clear cell change. A rare ductal structure with luminal proteinaceous contents was noted. The findings were consistent with a trichoepithelioma.

Trichoepitheliomas are rare, benign, adnexal skin tumors that can start in early childhood or during puberty. The lesions are most commonly seen in girls as skin color papules on the face, and sometimes on the trunk and the neck. Trichoepitheliomas can appear as a benign single lesion nonfamilial form or as a familial form with multiple lesions.¹ Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition where affected individuals have multiple trichoepitheliomas, cylindromas, and spiradenomas. Depending on the predominant type of lesion, phenotypic variants include multiple familial trichoepithelioma type 1 and familial cylindromatosis.² BSS is caused by mutations within CYLD, a tumor-suppressor gene located on chromosome 16q12-q13.³ Our patient presented only with trichoepitheliomas with no other lesions on the scalp, neck, or torso.

Multiple trichoepitheliomas also can be seen in other syndromes including Rombo syndrome, which is characterized by basal cell carcinomas, milia, hypotrichosis, distal vasodilation, and atrophoderma vermiculata; none seen in our patient. Bazex-Dupré-Christol syndrome is an X-linked dominant condition in which affected individuals can present with multiple trichoepitheliomas, as well as milia, hypotrichosis, follicular atrophoderma, and basal cell carcinomas.

The differential diagnosis of skin color papules on the central face on a child should include acne, flat warts, and angiofibromas seen in tuberous sclerosis. Our patient’s lesions were monomorphous, and there were no comedones, pustules, or inflammatory papules characteristic of acne.

He had warts on his hands which could make it suspicious for the face lesions to be verrucous in nature. Flat warts also present as skin color papules, but characteristically are flat, not round and shiny as our patient’s lesions were. Angiofibromas, as seen in individuals with tuberous sclerosis, also can start at an early age in the same location as trichoepitheliomas in BSS, but clinically the lesions are pinker and redder rather than the skin-color, round shape papules characteristic of trichoepitheliomas. Patients may have other findings suggestive of tuberous sclerosis including confetti hypopigmentation, ash leaf spots, shagreen patch, and a history of seizures or developmental delay – none of which were present in our patient. Children with basal cell nevus syndrome can present with skin color to shiny telangiectatic papules (basal cell carcinomas) that can be single or multiple on the face, chest, and back. The lesions usually are not seen in clusters around the nose and central face as seen in patients with BSS. Patients with basal cell nevus syndrome can develop jaw bone cysts, brain tumors (medulloblastoma), and fibromas on the heart or ovaries, palmar pits and be macrocephalic.⁴

Trichoepitheliomas usually are treated surgically but other nonsurgical removing techniques include laser resurfacing, curettage, and electrocautery.⁵ Malignant transformation can occur in 5%-10% of the individuals and should be managed by a multidisciplinary team. Topical treatment with sirolimus previously has been reported to be effective in young patients.⁶

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Acta Dermatovenerol Croat. 2018 Jun;26(2):162-5.

2. Eur J Med Genet. 2015;58(5):271-8.

3. Am J Dermatopathol. 2014;36(11):868-74.

4. Int J Dermatol. 2016 Apr;55(4):367-75.

5. Int J Dermatol. 2007;46(6):583-6.

6. Dermatol Ther. 2017 Mar. doi: 10.1111/dth.12458.