Dermatology

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 pdnews@mdedge.com.

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 pdnews@mdedge.com.

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 pdnews@mdedge.com.

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.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.

With record-high cases of measles throughout Europe, U.S. travelers to the region should be up to date on measles immunization and other recommended vaccines, researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.

CDC/Molly Kurnit, M.P.H.

More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.

France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.

“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.

But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.

Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.

“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”

“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.

In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.

“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.

“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”

Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.

Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.

The statement was funded by the CDC. The authors reported no relevant financial disclosures.

SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.

MILAN – Female patients who used systemic isotretinoin for acne saw a drop in markers for ovarian reserve, but the effect was reversed when treatment was stopped, according to data presented at the World Congress of Dermatology.

Wikimedia Commons/Kinan Ayu/Creative Commons

Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.

koakes@mdedge.com

MILAN – Female patients who used systemic isotretinoin for acne saw a drop in markers for ovarian reserve, but the effect was reversed when treatment was stopped, according to data presented at the World Congress of Dermatology.

Wikimedia Commons/Kinan Ayu/Creative Commons

Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.

koakes@mdedge.com

MILAN – Female patients who used systemic isotretinoin for acne saw a drop in markers for ovarian reserve, but the effect was reversed when treatment was stopped, according to data presented at the World Congress of Dermatology.

Wikimedia Commons/Kinan Ayu/Creative Commons

Dr. Akbulut reported no outside sources of funding and that she had no relevant financial disclosures.

koakes@mdedge.com

MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.

Mitchel L. Zoler/MDedge News

The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.

“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.

Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.

The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.

The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.

The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.


Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.

The safety results of the study were consistent with the known adverse effect profiles of both drugs.

The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.

“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.

SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.

mzoler@mdedge.com

SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.

MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.

Mitchel L. Zoler/MDedge News

The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.

“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.

Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.

The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.

The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.

The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.


Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.

The safety results of the study were consistent with the known adverse effect profiles of both drugs.

The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.

“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.

SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.

mzoler@mdedge.com

SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.

MADRID – The interleukin-17A inhibitor ixekizumab surpassed the tumor necrosis factor inhibitor adalimumab for treatment of patients with psoriatic arthritis in a multicenter, randomized study with 566 enrolled patients, the first reported results from a head-to-head comparison for this disease of two different classes of biological drugs.

Mitchel L. Zoler/MDedge News

The results showed that a standard, 24-week regimen with each of these agents, both of which already have regulatory approval for treating psoriatic arthritis (PsA), led to achievement of the primary endpoint in 36% of patients treated with ixekizumab (Taltz) and 28% of patients treated with adalimumab (Humira), a statistically significant difference, Philip J. Mease, MD, said at the European Congress of Rheumatology.

“Ixekizumab was superior to adalimumab for improving signs and symptoms of active PsA, as measured by simultaneous achievement of ACR50 [American College of Rheumatology] and PASI 100 [Psoriasis Area and Severity Index],” the study’s primary endpoint that combined a measure of joint disease activity with a measure of skin involvement, said Dr. Mease, a rheumatologist at Swedish Medical Center in Seattle.

This unconventional primary endpoint for testing drugs that treat PsA was called out during discussion of the report for having an inherent bias favoring ixekizumab by its inclusion of a skin outcome that received equal weight with an assessment tool that focused on joint responses. “This was a very unusual primary endpoint that favored ixekizumab,” Roy M. Fleischmann, MD, a Dallas rheumatologist, commented during the discussion.

Dr. Mease readily admitted that the study’s design stacked the deck in favor of ixekizumab, but he added that this decision reflected a desire by the researchers who ran the study to choose a primary endpoint that represented both of the prominent pathologies seen in patients with PsA.

The primary endpoint used in the study “looks at PsA more holistically,” Dr. Mease said in an interview. “It forced clinicians to look beyond just the joints,” in PsA patients. “That has been a limitation of prior PsA treatment assessments,” which until this study have uniformly used single primary outcomes that focus on joint responses, most commonly the ACR20 measure of joint disease activity.

The SPIRIT-H2H (A Study of Ixekizumab [LY2439821] Versus Adalimumab in Participants With Psoriatic Arthritis) study enrolled adults with active PsA who had never before received treatment with a biological drug. Enrolled patients had to have both active disease in their joints and active plaque psoriasis, with an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug. The 566 patients randomized in the study averaged about 48 years old, a bit more than half were men, and patients averaged about 6 years with diagnosed PsA and about 15 years diagnosed with psoriasis. Just over two-thirds of the patients were on concurrent treatment with a conventional synthetic agent, most often methotrexate.

The two components of the primary endpoint each showed the anticipated result. Among the 269 patients treated with adalimumab for the full 24 weeks, 47% had an ACR50 response, as did 51% of the 262 patients who completed their full course of ixekizumab, a between-group difference that was not statistically significant. In contrast, the PASI 100 measure of complete skin resolution occurred in 47% of the adalimumab-treated patients and 60% of those on ixekizumab, a statistically significant difference.


Dr. Mease reported results for several other efficacy measures, and what was notable was statistically significant superiority for ixekizumab in a measure of entheses disease activity, the SPARCC [Spondyloarthritis Research Consortium of Canada] Enthesitis Index, which fell to zero in 57% of the ixekizumab patients and 45% of those on adalimumab. “It makes you wonder whether there is something special about interleukin-17 in enthesitis,” Dr. Mease said.

The safety results of the study were consistent with the known adverse effect profiles of both drugs.

The impact of these findings on practice remains to be seen, and will likely depend on both cost considerations as well as clinicians trying to tailor drug choices to individual patients. The relatively new drug, ixekizumab, is consequentially more expensive than the older adalimumab, which has had its price depressed by the recent introduction of a biosimilar agent as well as long-standing competition from multiple TNF inhibitors.

“I think in the United States insurers will continue to steer patients toward whichever drug is cheapest among the highly-effective options,” but this result should lead to more use of interleukin-17 inhibitors as second-line agents for PsA, and it might push some clinicians to prescribe it as the first-line treatment, Dr. Mease said. He was confident that the efficacy profile shown by ixekizumab in SPIRIT-H2H was likely a class effect. Economics aside, the impetus to prescribe ixekizumab or another interleukin-17 inhibitor will be greatest when a patient has more extensive skin involvement, while for patients with little or no skin symptoms clinicians will likely stick with the more established TNF inhibitors as the first drug class to prescribe for PsA.

SPIRIT-H2H was sponsored by Eli Lilly, the company that markets ixekizumab (Taltz). Dr. Mease has been a consultant to, speaker for, and received research funding from Eli Lilly and from several other companies. Dr. Fleischmann has been a consultant to and has received research funding from several companies including Eli Lilly.

mzoler@mdedge.com

SOURCE: Mease PJ et al. Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709.