Dermatology

Two months ago I met Ed, still working at age 71. “My life’s ambition,” he said, “has been to help high school science teachers do their jobs better.”

“How’s it going?” I asked.

Ed sighed. “I’m still at it,” he said. “Let’s just say we’re not there yet.”

I too, dear colleagues, have had a life’s ambition, secret until right now: I wanted to eliminate erroneous fungal diagnosis. Or, to put it more pungently, to help nondermatologists stop treating every roundish scaly rash as ringworm.

Alas, like Ed’s, my work is not yet done.

I get reminders of this all the time, but last week the evidence got so overwhelming that I had to take a breath to settle down. And a nip. Ten cases. In 24 hours.

1. A 66-year-old woman energetically smeared econazole cream twice daily for weeks for an itchy, lichenified rash on both dorsal feet and ankles. Switched to betamethasone. Cleared in 5 days.

2. A 48-year-old woman with scaly patches on both legs. No response to terbinafine cream, then to ketoconazole cream, then to oral fluconazole. Cleared promptly on triamcinolone.

3. A 26-year-old with an erosive vulvar rash lasting month, unresponsive to Nystatin. After 5 days on a steroid, it was gone.

4. A 45-year-old man with lots of dermatoheliosis and idiopathic guttate hypomelanosis on arms and legs. No luck with topical selenium sulfide for tinea versicolor.

5. A 42-year-old nurse treated for weeks with topical antifungals. She came in with globs of fungus cream sealed in with Tegaderm (to prevent spread). Her roommates wanted to cancel her lease. Cleared of both rash and Tegaderm in 1 week. Now allowed to touch doorknobs.

6. A 27-year-old man with 8 weeks of lichenified patches all over his torso. Antifungal creams not working. Steroids do!

7. A 25-year-old recent émigré from India, where he was treated for his itchy groin rash with a succession of antifungal creams. He cannot sleep. (Imagine the plane trip from Delhi!) Has lichenified inguinal folds and scrotum. Cleared in 1 week with a topical steroid.

8. A 22-year-old woman with widespread atopic dermatitis. No response to antifungals. She had a rash at age 2 that was called “allergy to shampoo.” Clears promptly on a steroid.

9. A 22-year-old man being treated for a scaly, bilateral periocular rash with oral cephalexin. Clears promptly on a weak topical steroid.

10. A 29-year-old woman who has been suffering for months with “sensitivity” of her vulvar skin that has been diagnosed and treated as “a yeast infection,” in the absence of any rash or discharge. Her only visible finding is inverse psoriasis in the gluteal cleft. Guess what clears her up?

And so it goes, and so it has gone, week after week, year after year, decade after decade. Medicine scales Olympus: genomics, immunotherapy, stereotactic surgery. Meantime, the it’s-not-a-fungus problem seems impervious to both education and even to daily observation as obvious as it is ineffective: If a supposed fungus does not respond to antifungal treatment, then it must be a very bad fungus. If it doesn’t respond to yet another antifungal cream, then it must be terrible fungus. Reconsidering that it may not be a fungus at all seems to demand a mental paradigm shift whose achievement will have to await a more discerning generation.

In the meantime, patients not only don’t get better, but they feel defiled and dirty. They avoid human contact, intimate and otherwise, and do a lot of superfluous and expensive cleaning of house and wardrobe. If you doubt this, ask them. If you think I overstate, spend a day with me.

Early in my career I inherited the once-yearly dermatology slot at Medical Grand Rounds at the local community hospital. I spoke about cutaneous fungus, with emphasis on the fact that lots of round rashes are nummular eczema rather than fungus, as well as what it means to patients to be told they are “fungal.”

I didn’t get much direct feedback, but the chief of medicine sprang into action. He canceled the dermatology slot. Not medical enough, I guess.

Ed tells me that many high school science teachers don’t know much science. They teach it because they thought they might like to, or because there was an opening. After Ed hangs up his cleats, there will be plenty of his work left to be done.

But then, there always is.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Two months ago I met Ed, still working at age 71. “My life’s ambition,” he said, “has been to help high school science teachers do their jobs better.”

“How’s it going?” I asked.

Ed sighed. “I’m still at it,” he said. “Let’s just say we’re not there yet.”

I too, dear colleagues, have had a life’s ambition, secret until right now: I wanted to eliminate erroneous fungal diagnosis. Or, to put it more pungently, to help nondermatologists stop treating every roundish scaly rash as ringworm.

Alas, like Ed’s, my work is not yet done.

I get reminders of this all the time, but last week the evidence got so overwhelming that I had to take a breath to settle down. And a nip. Ten cases. In 24 hours.

1. A 66-year-old woman energetically smeared econazole cream twice daily for weeks for an itchy, lichenified rash on both dorsal feet and ankles. Switched to betamethasone. Cleared in 5 days.

2. A 48-year-old woman with scaly patches on both legs. No response to terbinafine cream, then to ketoconazole cream, then to oral fluconazole. Cleared promptly on triamcinolone.

3. A 26-year-old with an erosive vulvar rash lasting month, unresponsive to Nystatin. After 5 days on a steroid, it was gone.

4. A 45-year-old man with lots of dermatoheliosis and idiopathic guttate hypomelanosis on arms and legs. No luck with topical selenium sulfide for tinea versicolor.

5. A 42-year-old nurse treated for weeks with topical antifungals. She came in with globs of fungus cream sealed in with Tegaderm (to prevent spread). Her roommates wanted to cancel her lease. Cleared of both rash and Tegaderm in 1 week. Now allowed to touch doorknobs.

6. A 27-year-old man with 8 weeks of lichenified patches all over his torso. Antifungal creams not working. Steroids do!

7. A 25-year-old recent émigré from India, where he was treated for his itchy groin rash with a succession of antifungal creams. He cannot sleep. (Imagine the plane trip from Delhi!) Has lichenified inguinal folds and scrotum. Cleared in 1 week with a topical steroid.

8. A 22-year-old woman with widespread atopic dermatitis. No response to antifungals. She had a rash at age 2 that was called “allergy to shampoo.” Clears promptly on a steroid.

9. A 22-year-old man being treated for a scaly, bilateral periocular rash with oral cephalexin. Clears promptly on a weak topical steroid.

10. A 29-year-old woman who has been suffering for months with “sensitivity” of her vulvar skin that has been diagnosed and treated as “a yeast infection,” in the absence of any rash or discharge. Her only visible finding is inverse psoriasis in the gluteal cleft. Guess what clears her up?

And so it goes, and so it has gone, week after week, year after year, decade after decade. Medicine scales Olympus: genomics, immunotherapy, stereotactic surgery. Meantime, the it’s-not-a-fungus problem seems impervious to both education and even to daily observation as obvious as it is ineffective: If a supposed fungus does not respond to antifungal treatment, then it must be a very bad fungus. If it doesn’t respond to yet another antifungal cream, then it must be terrible fungus. Reconsidering that it may not be a fungus at all seems to demand a mental paradigm shift whose achievement will have to await a more discerning generation.

In the meantime, patients not only don’t get better, but they feel defiled and dirty. They avoid human contact, intimate and otherwise, and do a lot of superfluous and expensive cleaning of house and wardrobe. If you doubt this, ask them. If you think I overstate, spend a day with me.

Early in my career I inherited the once-yearly dermatology slot at Medical Grand Rounds at the local community hospital. I spoke about cutaneous fungus, with emphasis on the fact that lots of round rashes are nummular eczema rather than fungus, as well as what it means to patients to be told they are “fungal.”

I didn’t get much direct feedback, but the chief of medicine sprang into action. He canceled the dermatology slot. Not medical enough, I guess.

Ed tells me that many high school science teachers don’t know much science. They teach it because they thought they might like to, or because there was an opening. After Ed hangs up his cleats, there will be plenty of his work left to be done.

But then, there always is.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Two months ago I met Ed, still working at age 71. “My life’s ambition,” he said, “has been to help high school science teachers do their jobs better.”

“How’s it going?” I asked.

Ed sighed. “I’m still at it,” he said. “Let’s just say we’re not there yet.”

I too, dear colleagues, have had a life’s ambition, secret until right now: I wanted to eliminate erroneous fungal diagnosis. Or, to put it more pungently, to help nondermatologists stop treating every roundish scaly rash as ringworm.

Alas, like Ed’s, my work is not yet done.

I get reminders of this all the time, but last week the evidence got so overwhelming that I had to take a breath to settle down. And a nip. Ten cases. In 24 hours.

1. A 66-year-old woman energetically smeared econazole cream twice daily for weeks for an itchy, lichenified rash on both dorsal feet and ankles. Switched to betamethasone. Cleared in 5 days.

2. A 48-year-old woman with scaly patches on both legs. No response to terbinafine cream, then to ketoconazole cream, then to oral fluconazole. Cleared promptly on triamcinolone.

3. A 26-year-old with an erosive vulvar rash lasting month, unresponsive to Nystatin. After 5 days on a steroid, it was gone.

4. A 45-year-old man with lots of dermatoheliosis and idiopathic guttate hypomelanosis on arms and legs. No luck with topical selenium sulfide for tinea versicolor.

5. A 42-year-old nurse treated for weeks with topical antifungals. She came in with globs of fungus cream sealed in with Tegaderm (to prevent spread). Her roommates wanted to cancel her lease. Cleared of both rash and Tegaderm in 1 week. Now allowed to touch doorknobs.

6. A 27-year-old man with 8 weeks of lichenified patches all over his torso. Antifungal creams not working. Steroids do!

7. A 25-year-old recent émigré from India, where he was treated for his itchy groin rash with a succession of antifungal creams. He cannot sleep. (Imagine the plane trip from Delhi!) Has lichenified inguinal folds and scrotum. Cleared in 1 week with a topical steroid.

8. A 22-year-old woman with widespread atopic dermatitis. No response to antifungals. She had a rash at age 2 that was called “allergy to shampoo.” Clears promptly on a steroid.

9. A 22-year-old man being treated for a scaly, bilateral periocular rash with oral cephalexin. Clears promptly on a weak topical steroid.

10. A 29-year-old woman who has been suffering for months with “sensitivity” of her vulvar skin that has been diagnosed and treated as “a yeast infection,” in the absence of any rash or discharge. Her only visible finding is inverse psoriasis in the gluteal cleft. Guess what clears her up?

And so it goes, and so it has gone, week after week, year after year, decade after decade. Medicine scales Olympus: genomics, immunotherapy, stereotactic surgery. Meantime, the it’s-not-a-fungus problem seems impervious to both education and even to daily observation as obvious as it is ineffective: If a supposed fungus does not respond to antifungal treatment, then it must be a very bad fungus. If it doesn’t respond to yet another antifungal cream, then it must be terrible fungus. Reconsidering that it may not be a fungus at all seems to demand a mental paradigm shift whose achievement will have to await a more discerning generation.

In the meantime, patients not only don’t get better, but they feel defiled and dirty. They avoid human contact, intimate and otherwise, and do a lot of superfluous and expensive cleaning of house and wardrobe. If you doubt this, ask them. If you think I overstate, spend a day with me.

Early in my career I inherited the once-yearly dermatology slot at Medical Grand Rounds at the local community hospital. I spoke about cutaneous fungus, with emphasis on the fact that lots of round rashes are nummular eczema rather than fungus, as well as what it means to patients to be told they are “fungal.”

I didn’t get much direct feedback, but the chief of medicine sprang into action. He canceled the dermatology slot. Not medical enough, I guess.

Ed tells me that many high school science teachers don’t know much science. They teach it because they thought they might like to, or because there was an opening. After Ed hangs up his cleats, there will be plenty of his work left to be done.

But then, there always is.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

The FP recognized that this could be a wart but was concerned that it might be a squamous cell carcinoma (SCC) related to HPV and sun exposure.

He performed a shave biopsy and the pathology report indicated it was an SCC in situ. (See the Watch & Learn video on “Shave biopsy.”)  At the follow-up visit, the FP reviewed the patient’s treatment options, which included topical 5% fluorouracil, topical imiquimod, and surgical excision. He also explained that the topical treatments were off label, so these options might have a lower success rate than the surgery.

The patient chose to have the surgery, even though he’d be out of work while the excision site was healing. The FP provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun. He also referred the patient to a dermatologist who had extensive experience doing skin cancer surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized that this could be a wart but was concerned that it might be a squamous cell carcinoma (SCC) related to HPV and sun exposure.

He performed a shave biopsy and the pathology report indicated it was an SCC in situ. (See the Watch & Learn video on “Shave biopsy.”)  At the follow-up visit, the FP reviewed the patient’s treatment options, which included topical 5% fluorouracil, topical imiquimod, and surgical excision. He also explained that the topical treatments were off label, so these options might have a lower success rate than the surgery.

The patient chose to have the surgery, even though he’d be out of work while the excision site was healing. The FP provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun. He also referred the patient to a dermatologist who had extensive experience doing skin cancer surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized that this could be a wart but was concerned that it might be a squamous cell carcinoma (SCC) related to HPV and sun exposure.

He performed a shave biopsy and the pathology report indicated it was an SCC in situ. (See the Watch & Learn video on “Shave biopsy.”)  At the follow-up visit, the FP reviewed the patient’s treatment options, which included topical 5% fluorouracil, topical imiquimod, and surgical excision. He also explained that the topical treatments were off label, so these options might have a lower success rate than the surgery.

The patient chose to have the surgery, even though he’d be out of work while the excision site was healing. The FP provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun. He also referred the patient to a dermatologist who had extensive experience doing skin cancer surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Patients with atopic dermatitis might face up to a 44% increased risk of suicidal ideation and are 36% more likely to attempt suicide than those without the disorder, a large meta-analysis has determined.

aniaostudio/Thinkstock.com

The analysis, which included data from studies published as far back as 1945, also found some correlation of increased suicide risk and increasing disease severity, although the numbers were small, Jeena K. Sandhu and her colleagues reported in JAMA Dermatology.

Both physical and psychological factors could be involved in the link, wrote Ms. Sandhu, a medical student at the University of Missouri–Kansas City, and her coauthors.

“Atopic dermatitis is associated with multiple physical comorbidities, such as asthma, allergic rhinitis, metabolic syndrome, and sleep disturbances, which all contribute to the overall physical burden of the disease. Many patients also have a profound psychosocial burden. Because of the visibility of the disease, patients may experience shame, embarrassment, and stigmatization,” they wrote.

But the disease also is associated with high levels of proinflammatory cytokines, and those proteins have been isolated in the cerebrospinal fluid of patients who have attempted suicide, the investigators noted. “Treatments targeting cytokines, such as interleukin-4 and interleukin-13, have been shown to decrease symptoms of depression and anxiety in patients with atopic dermatitis.”

The investigators plumbed several databases of medical literature, searching for studies that mentioned both atopic dermatitis (AD) and suicide, suicidal ideation, or suicidal behavior. They found 15 studies, published from 1945 to May 2018. Most (13) were cross sectional; the remainder were cohort studies. Together, they comprised a total of 4.7 million subjects, 310,681 of whom had AD. The analysis looked at risks in three areas: suicidal ideation, suicide attempts, and completed suicides.

Of the studies, 11 investigated suicidal ideation. Pooled data determined that patients with AD were a significant 44% more likely to experience suicidal ideation than those without the disease.

Three studies mentioned suicide attempts and had complete data for pooling. Taken together, they showed a significant 36% increased risk of attempted suicide among patients with AD, compared with those without the disorder.

Two studies investigated the prevalence of completed suicides among patients. One did report a significantly increased risk of 40%, compared with the control group, but it failed to report the number of suicides in the control group. The other study found no increased risk of completed suicides in patients with either mild or moderate to severe disease, compared with controls.

Two studies involved only pediatric patients. One, conducted in Korea, found a significant 23% increased risk of suicidal ideation and a 31% increased risk of attempted suicide. The other failed to find any increased risks in the overall analysis, but did find small increases in the risks of ideation and attempt in girls with AD, compared with healthy controls.

“Monitoring for suicidality in patients with atopic dermatitis is crucial to improving patient outcomes,” the team concluded. “Dermatology providers may use several tools to screen patients for suicidality. Asking patients about suicidal ideation with a question may be integrated into a patient visit. If a patient screens positive for suicidality, the dermatology provider should send a referral to the patient’s primary care or mental health provider for follow-up care. If the patient reports an orchestrated plan to commit suicide, this patient should be urgently referred to the emergency department for further assessment.”

Ms. Sandhu reported no financial disclosures.

[email protected]

SOURCE: Sandhu JK et al. JAMA Dermatol. 2018 Dec 12. doi: 10.1001/jamadermatol.2018.4566.

Patients with atopic dermatitis might face up to a 44% increased risk of suicidal ideation and are 36% more likely to attempt suicide than those without the disorder, a large meta-analysis has determined.

aniaostudio/Thinkstock.com

The analysis, which included data from studies published as far back as 1945, also found some correlation of increased suicide risk and increasing disease severity, although the numbers were small, Jeena K. Sandhu and her colleagues reported in JAMA Dermatology.

Both physical and psychological factors could be involved in the link, wrote Ms. Sandhu, a medical student at the University of Missouri–Kansas City, and her coauthors.

“Atopic dermatitis is associated with multiple physical comorbidities, such as asthma, allergic rhinitis, metabolic syndrome, and sleep disturbances, which all contribute to the overall physical burden of the disease. Many patients also have a profound psychosocial burden. Because of the visibility of the disease, patients may experience shame, embarrassment, and stigmatization,” they wrote.

But the disease also is associated with high levels of proinflammatory cytokines, and those proteins have been isolated in the cerebrospinal fluid of patients who have attempted suicide, the investigators noted. “Treatments targeting cytokines, such as interleukin-4 and interleukin-13, have been shown to decrease symptoms of depression and anxiety in patients with atopic dermatitis.”

The investigators plumbed several databases of medical literature, searching for studies that mentioned both atopic dermatitis (AD) and suicide, suicidal ideation, or suicidal behavior. They found 15 studies, published from 1945 to May 2018. Most (13) were cross sectional; the remainder were cohort studies. Together, they comprised a total of 4.7 million subjects, 310,681 of whom had AD. The analysis looked at risks in three areas: suicidal ideation, suicide attempts, and completed suicides.

Of the studies, 11 investigated suicidal ideation. Pooled data determined that patients with AD were a significant 44% more likely to experience suicidal ideation than those without the disease.

Three studies mentioned suicide attempts and had complete data for pooling. Taken together, they showed a significant 36% increased risk of attempted suicide among patients with AD, compared with those without the disorder.

Two studies investigated the prevalence of completed suicides among patients. One did report a significantly increased risk of 40%, compared with the control group, but it failed to report the number of suicides in the control group. The other study found no increased risk of completed suicides in patients with either mild or moderate to severe disease, compared with controls.

Two studies involved only pediatric patients. One, conducted in Korea, found a significant 23% increased risk of suicidal ideation and a 31% increased risk of attempted suicide. The other failed to find any increased risks in the overall analysis, but did find small increases in the risks of ideation and attempt in girls with AD, compared with healthy controls.

“Monitoring for suicidality in patients with atopic dermatitis is crucial to improving patient outcomes,” the team concluded. “Dermatology providers may use several tools to screen patients for suicidality. Asking patients about suicidal ideation with a question may be integrated into a patient visit. If a patient screens positive for suicidality, the dermatology provider should send a referral to the patient’s primary care or mental health provider for follow-up care. If the patient reports an orchestrated plan to commit suicide, this patient should be urgently referred to the emergency department for further assessment.”

Ms. Sandhu reported no financial disclosures.

[email protected]

SOURCE: Sandhu JK et al. JAMA Dermatol. 2018 Dec 12. doi: 10.1001/jamadermatol.2018.4566.

Patients with atopic dermatitis might face up to a 44% increased risk of suicidal ideation and are 36% more likely to attempt suicide than those without the disorder, a large meta-analysis has determined.

aniaostudio/Thinkstock.com

The analysis, which included data from studies published as far back as 1945, also found some correlation of increased suicide risk and increasing disease severity, although the numbers were small, Jeena K. Sandhu and her colleagues reported in JAMA Dermatology.

Both physical and psychological factors could be involved in the link, wrote Ms. Sandhu, a medical student at the University of Missouri–Kansas City, and her coauthors.

“Atopic dermatitis is associated with multiple physical comorbidities, such as asthma, allergic rhinitis, metabolic syndrome, and sleep disturbances, which all contribute to the overall physical burden of the disease. Many patients also have a profound psychosocial burden. Because of the visibility of the disease, patients may experience shame, embarrassment, and stigmatization,” they wrote.

But the disease also is associated with high levels of proinflammatory cytokines, and those proteins have been isolated in the cerebrospinal fluid of patients who have attempted suicide, the investigators noted. “Treatments targeting cytokines, such as interleukin-4 and interleukin-13, have been shown to decrease symptoms of depression and anxiety in patients with atopic dermatitis.”

The investigators plumbed several databases of medical literature, searching for studies that mentioned both atopic dermatitis (AD) and suicide, suicidal ideation, or suicidal behavior. They found 15 studies, published from 1945 to May 2018. Most (13) were cross sectional; the remainder were cohort studies. Together, they comprised a total of 4.7 million subjects, 310,681 of whom had AD. The analysis looked at risks in three areas: suicidal ideation, suicide attempts, and completed suicides.

Of the studies, 11 investigated suicidal ideation. Pooled data determined that patients with AD were a significant 44% more likely to experience suicidal ideation than those without the disease.

Three studies mentioned suicide attempts and had complete data for pooling. Taken together, they showed a significant 36% increased risk of attempted suicide among patients with AD, compared with those without the disorder.

Two studies investigated the prevalence of completed suicides among patients. One did report a significantly increased risk of 40%, compared with the control group, but it failed to report the number of suicides in the control group. The other study found no increased risk of completed suicides in patients with either mild or moderate to severe disease, compared with controls.

Two studies involved only pediatric patients. One, conducted in Korea, found a significant 23% increased risk of suicidal ideation and a 31% increased risk of attempted suicide. The other failed to find any increased risks in the overall analysis, but did find small increases in the risks of ideation and attempt in girls with AD, compared with healthy controls.

“Monitoring for suicidality in patients with atopic dermatitis is crucial to improving patient outcomes,” the team concluded. “Dermatology providers may use several tools to screen patients for suicidality. Asking patients about suicidal ideation with a question may be integrated into a patient visit. If a patient screens positive for suicidality, the dermatology provider should send a referral to the patient’s primary care or mental health provider for follow-up care. If the patient reports an orchestrated plan to commit suicide, this patient should be urgently referred to the emergency department for further assessment.”

Ms. Sandhu reported no financial disclosures.

[email protected]

SOURCE: Sandhu JK et al. JAMA Dermatol. 2018 Dec 12. doi: 10.1001/jamadermatol.2018.4566.

The FP had seen many recalcitrant warts before, but rather than repeat the cryotherapy, he performed a shave biopsy to get a definitive diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The biopsy revealed a well-differentiated squamous cell carcinoma (SCC).

This lesion may have started with a wart, as human papillomavirus (HPV) is both the cause of warts and a risk factor for cutaneous SCC. The FP referred the patient to a Mohs surgeon for complete excision of the SCC. He also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP had seen many recalcitrant warts before, but rather than repeat the cryotherapy, he performed a shave biopsy to get a definitive diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The biopsy revealed a well-differentiated squamous cell carcinoma (SCC).

This lesion may have started with a wart, as human papillomavirus (HPV) is both the cause of warts and a risk factor for cutaneous SCC. The FP referred the patient to a Mohs surgeon for complete excision of the SCC. He also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP had seen many recalcitrant warts before, but rather than repeat the cryotherapy, he performed a shave biopsy to get a definitive diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The biopsy revealed a well-differentiated squamous cell carcinoma (SCC).

This lesion may have started with a wart, as human papillomavirus (HPV) is both the cause of warts and a risk factor for cutaneous SCC. The FP referred the patient to a Mohs surgeon for complete excision of the SCC. He also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Many years ago, when I was still in primary care (internal medicine), I thought I knew a bit about the practice of medicine. I was totally comfortable in the hospital (in those days, we saw our own patients twice a day in the hospital), including the ER, the OR, even obstetrics. MIs, shootings, stab wounds, renal failure—I would never say I had mastered them, but I was comfortable with most of what I saw. Deliveries, assisting with C-sections, performing lumbar punctures, performing and interpreting exercise tolerance tests, performing flexible sigmoidoscopies—no problem.

But the one thing that nearly always stopped me in my tracks was … you guessed it: dermatology complaints. Rashes, lesions, or any other skin complaint the least bit out of the ordinary were completely baffling to me. I still remember that feeling after all these years (and I still occasionally experience it!).

I felt like saying to those patients: What in the world would make you think I’d have any idea what that is? But of course, I couldn’t say that, so I’d mumble something, throw some cream at it, then quickly change the subject. Mind you, this was in a setting where a derm referral from us would take 4 to 6 months. And in case you’re wondering, the other providers in my department were as bad at derm as I was.

Long story short, it got to the point that I would scan my schedule every morning, praying I wouldn’t see the word “rash” or “skin.” But, of course, they still came—often just as my hand touched the doorknob to leave: “Oh, by the way, what about this …?” You get the picture. Many of you, if not most, live that picture.

I finally got up the nerve to go to our dermatology department to ask if I could follow one of the docs while he saw patients. Little did I know that practically every provider in the building had already done the same, and had been dismissed with words that essentially meant, “You? A mere PA? You can’t get there from here. Just send ’em to us.”

For a short time, I bought that line—but in the meantime, my patients were not getting the care they needed. So, driven in part by anger at the notion that a mere PA was simply unable to learn dermatology, I bought a decent textbook, Fitzpatrick’s Color Atlas of Dermatology, and started reading it. I also started collecting all the derm articles I could find in the journals, and read about those cases.

I won’t bore you with the grimy details, but what I did differently was work at learning derm (what a concept!). I started going to derm conferences, bought a good camera and started taking pictures with it, and continued to buy books (this was in the pre-computer days of the ’80s) and actually read them.

Continue to: And a funny thing happened...

And a funny thing happened: The more I read, the more diagnoses I recognized on my patients. My colleagues and the clinic schedulers took note of this and began sending me their problem cases. Even the derm department, beleaguered as usual by huge backlogs of patients, started sending patients to me. By 1985, even though I was in the internal medicine department, I had transitioned to doing derm fulltime. And that’s what I’ve been doing since.

Around 1992, I discovered that I was one of 6 dermatology PAs in this country. Last time I checked, our numbers were approaching 4,000. So, yes, derm is indeed difficult, but rocket science it isn’t.

Being the pedantic sort that I am, and finding that whole experience so enlightening, I resolved to make it my mission to foster the use of PAs in dermatology—part of which involves the education of those PAs, by means of taking students but also by writing articles (several hundred at last count) and lecturing at conferences and at PA programs. Nearing retirement, I only practice two days a week, but I write and publish at least 5 clinical articles a month, all of which are based on real cases: my cases, using my photos, doing new research on each case. This keeps my knowledge fresh and my 75-year-old mind sharp, helps ward off burnout, and, most importantly, saves lives while reducing patient discomfort.

What follows are 10 dermatology pearls that I have gleaned along the way. My apologies to my former students and attendees at my lectures who’ve heard all this before:

1 If the treatment for your diagnosis isn’t working, consider another diagnosis. Here’s an example (Figure 1): A man in his 50s was sent to dermatology for psoriasis that wasn’t responding to a biologic. Was it really psoriasis? A KOH prep quickly showed it to be tinea corporis, which cleared completely with a month’s worth of oral terbinafine (250 mg qid).

Continue to: #2...

2 The correct diagnosis dictates correct treatment. This may sound obvious, but in primary care, the emphasis is often on “let’s try this” or “let’s try that,” an understandable approach to a symptomatic patient with an uncertain diagnosis. But by the time he finally gets to dermatology, the patient has tried a whole bag full of prescription and OTC products given for numerous, totally different diagnoses. A better approach might be to expedite an urgent referral to dermatology, when possible.

3 Cutaneous fungal infections (ie, dermatophytosis) are vastly overdiagnosed, especially by novices. If you truly suspect it, ask about a potential source; one doesn’t acquire a fungal infection out of thin air. It must come from a person, animal, or occasionally, the soil. It also helps if the victim has been rendered susceptible by the injudicious use of steroids. Better yet, find the fungus with a microscopic examination (KOH prep) or culture. Finally, remember, not everything round and scaly is fungal (see Figure 2).

4 Remember these ancient words of wisdom regarding skin complaints: (a) A diagnosis is seldom made if not entertained, (b) you won’t entertain it if you’ve never heard of it, (c) you will not see it if you’re not looking for it, and (d) even if you did see it, you would not “see” it because you’re not looking for it. Dermatology is far deeper and wider than most imagine it to be. The trick is to expose yourself to as many different diagnoses as possible, by reading and attending lectures, ahead of the possible sighting. Figures 3 and 4 offer examples of common conditions that are seldom recognized outside dermatology.

5 Skin cancer can present as a rash. Examples abound, such as mammary and extramammary Paget’s disease (Figure 5), mycosis fungoides, metastatic breast cancer (Figure 6), and superficial basal cell carcinoma. A biopsy is usually required to diagnose these, but you wouldn’t think to do that if you’d never heard of the condition.

6 Melanoma doesn’t typically arise from a mole or other pre-existing lesion. Far more often, it arises “de novo,” out of nothing. So, in general, we’re not worried about “moles” (nevi) unless there’s a history of change (see Figure 7).

Continue to: #7...

7 When looking for skin cancer, pay as much attention to the owner as to the lesion. The most common skin cancers—basal cell and squamous cell carcinoma—usually occur on sun-damaged, fair-skinned, blue-eyed older patients. Though there are certainly exceptions to this paradigm, it pays to be generally suspicious of any odd lesion seen on these patients (Figure 8).

8 It’s practically impossible to overstate the role of atopy when evaluating pediatric skin complaints. These children—20% of all newborns!—are born with thin, dry, sensitive, overreactive skin that is prone to eczema and urticaria. They will also have a marked tendency to develop seasonal allergies, allergic rhinitis, and asthma. Parents find it difficult to accept the genetic basis for atopic dermatitis (Figure 9), preferring instead to blame everything on laundry detergent or food. Education (of oneself first!) is the key.

9 “Infections” are not always what they seem. These pearls may help: a) There are many causes of localized erythema, swelling, and tenderness that have nothing to do with infection. Examples include relapsing polychondritis (Figure 10) and cutaneous lupus (Figure 11). b) Skin cancer, such as basal cell carcinoma (see Figure 12), is often mistaken for infection. c) Some infections have less conventional or obvious sources; those caused by atypical mycobacteria (see Figure 13), leishmaniasis (see Figure 14), and sporothrix (see Figure 15), are good examples of this phenomenon. Consider thinking outside the box.

10 Overcome your fear of steroids by educating yourself about their safe use. Glucocorticoids (eg, triamcinolone, prednisone, betamethasone) are extremely useful in treating common derm conditions. We see patients every day who are so frightened of steroids, they won’t even consider using them because some well-meaning medical provider scared them to death. The proper use of these miraculous products could easily be the subject of an entire article. For now, I’ll advise you to read about their safe use in any number of dermatology texts (including online publications).

Many years ago, when I was still in primary care (internal medicine), I thought I knew a bit about the practice of medicine. I was totally comfortable in the hospital (in those days, we saw our own patients twice a day in the hospital), including the ER, the OR, even obstetrics. MIs, shootings, stab wounds, renal failure—I would never say I had mastered them, but I was comfortable with most of what I saw. Deliveries, assisting with C-sections, performing lumbar punctures, performing and interpreting exercise tolerance tests, performing flexible sigmoidoscopies—no problem.

But the one thing that nearly always stopped me in my tracks was … you guessed it: dermatology complaints. Rashes, lesions, or any other skin complaint the least bit out of the ordinary were completely baffling to me. I still remember that feeling after all these years (and I still occasionally experience it!).

I felt like saying to those patients: What in the world would make you think I’d have any idea what that is? But of course, I couldn’t say that, so I’d mumble something, throw some cream at it, then quickly change the subject. Mind you, this was in a setting where a derm referral from us would take 4 to 6 months. And in case you’re wondering, the other providers in my department were as bad at derm as I was.

Long story short, it got to the point that I would scan my schedule every morning, praying I wouldn’t see the word “rash” or “skin.” But, of course, they still came—often just as my hand touched the doorknob to leave: “Oh, by the way, what about this …?” You get the picture. Many of you, if not most, live that picture.

I finally got up the nerve to go to our dermatology department to ask if I could follow one of the docs while he saw patients. Little did I know that practically every provider in the building had already done the same, and had been dismissed with words that essentially meant, “You? A mere PA? You can’t get there from here. Just send ’em to us.”

For a short time, I bought that line—but in the meantime, my patients were not getting the care they needed. So, driven in part by anger at the notion that a mere PA was simply unable to learn dermatology, I bought a decent textbook, Fitzpatrick’s Color Atlas of Dermatology, and started reading it. I also started collecting all the derm articles I could find in the journals, and read about those cases.

I won’t bore you with the grimy details, but what I did differently was work at learning derm (what a concept!). I started going to derm conferences, bought a good camera and started taking pictures with it, and continued to buy books (this was in the pre-computer days of the ’80s) and actually read them.

Continue to: And a funny thing happened...

And a funny thing happened: The more I read, the more diagnoses I recognized on my patients. My colleagues and the clinic schedulers took note of this and began sending me their problem cases. Even the derm department, beleaguered as usual by huge backlogs of patients, started sending patients to me. By 1985, even though I was in the internal medicine department, I had transitioned to doing derm fulltime. And that’s what I’ve been doing since.

Around 1992, I discovered that I was one of 6 dermatology PAs in this country. Last time I checked, our numbers were approaching 4,000. So, yes, derm is indeed difficult, but rocket science it isn’t.

Being the pedantic sort that I am, and finding that whole experience so enlightening, I resolved to make it my mission to foster the use of PAs in dermatology—part of which involves the education of those PAs, by means of taking students but also by writing articles (several hundred at last count) and lecturing at conferences and at PA programs. Nearing retirement, I only practice two days a week, but I write and publish at least 5 clinical articles a month, all of which are based on real cases: my cases, using my photos, doing new research on each case. This keeps my knowledge fresh and my 75-year-old mind sharp, helps ward off burnout, and, most importantly, saves lives while reducing patient discomfort.

What follows are 10 dermatology pearls that I have gleaned along the way. My apologies to my former students and attendees at my lectures who’ve heard all this before:

1 If the treatment for your diagnosis isn’t working, consider another diagnosis. Here’s an example (Figure 1): A man in his 50s was sent to dermatology for psoriasis that wasn’t responding to a biologic. Was it really psoriasis? A KOH prep quickly showed it to be tinea corporis, which cleared completely with a month’s worth of oral terbinafine (250 mg qid).

Continue to: #2...

2 The correct diagnosis dictates correct treatment. This may sound obvious, but in primary care, the emphasis is often on “let’s try this” or “let’s try that,” an understandable approach to a symptomatic patient with an uncertain diagnosis. But by the time he finally gets to dermatology, the patient has tried a whole bag full of prescription and OTC products given for numerous, totally different diagnoses. A better approach might be to expedite an urgent referral to dermatology, when possible.

3 Cutaneous fungal infections (ie, dermatophytosis) are vastly overdiagnosed, especially by novices. If you truly suspect it, ask about a potential source; one doesn’t acquire a fungal infection out of thin air. It must come from a person, animal, or occasionally, the soil. It also helps if the victim has been rendered susceptible by the injudicious use of steroids. Better yet, find the fungus with a microscopic examination (KOH prep) or culture. Finally, remember, not everything round and scaly is fungal (see Figure 2).

4 Remember these ancient words of wisdom regarding skin complaints: (a) A diagnosis is seldom made if not entertained, (b) you won’t entertain it if you’ve never heard of it, (c) you will not see it if you’re not looking for it, and (d) even if you did see it, you would not “see” it because you’re not looking for it. Dermatology is far deeper and wider than most imagine it to be. The trick is to expose yourself to as many different diagnoses as possible, by reading and attending lectures, ahead of the possible sighting. Figures 3 and 4 offer examples of common conditions that are seldom recognized outside dermatology.

5 Skin cancer can present as a rash. Examples abound, such as mammary and extramammary Paget’s disease (Figure 5), mycosis fungoides, metastatic breast cancer (Figure 6), and superficial basal cell carcinoma. A biopsy is usually required to diagnose these, but you wouldn’t think to do that if you’d never heard of the condition.

6 Melanoma doesn’t typically arise from a mole or other pre-existing lesion. Far more often, it arises “de novo,” out of nothing. So, in general, we’re not worried about “moles” (nevi) unless there’s a history of change (see Figure 7).

Continue to: #7...

7 When looking for skin cancer, pay as much attention to the owner as to the lesion. The most common skin cancers—basal cell and squamous cell carcinoma—usually occur on sun-damaged, fair-skinned, blue-eyed older patients. Though there are certainly exceptions to this paradigm, it pays to be generally suspicious of any odd lesion seen on these patients (Figure 8).

8 It’s practically impossible to overstate the role of atopy when evaluating pediatric skin complaints. These children—20% of all newborns!—are born with thin, dry, sensitive, overreactive skin that is prone to eczema and urticaria. They will also have a marked tendency to develop seasonal allergies, allergic rhinitis, and asthma. Parents find it difficult to accept the genetic basis for atopic dermatitis (Figure 9), preferring instead to blame everything on laundry detergent or food. Education (of oneself first!) is the key.

9 “Infections” are not always what they seem. These pearls may help: a) There are many causes of localized erythema, swelling, and tenderness that have nothing to do with infection. Examples include relapsing polychondritis (Figure 10) and cutaneous lupus (Figure 11). b) Skin cancer, such as basal cell carcinoma (see Figure 12), is often mistaken for infection. c) Some infections have less conventional or obvious sources; those caused by atypical mycobacteria (see Figure 13), leishmaniasis (see Figure 14), and sporothrix (see Figure 15), are good examples of this phenomenon. Consider thinking outside the box.

10 Overcome your fear of steroids by educating yourself about their safe use. Glucocorticoids (eg, triamcinolone, prednisone, betamethasone) are extremely useful in treating common derm conditions. We see patients every day who are so frightened of steroids, they won’t even consider using them because some well-meaning medical provider scared them to death. The proper use of these miraculous products could easily be the subject of an entire article. For now, I’ll advise you to read about their safe use in any number of dermatology texts (including online publications).

Many years ago, when I was still in primary care (internal medicine), I thought I knew a bit about the practice of medicine. I was totally comfortable in the hospital (in those days, we saw our own patients twice a day in the hospital), including the ER, the OR, even obstetrics. MIs, shootings, stab wounds, renal failure—I would never say I had mastered them, but I was comfortable with most of what I saw. Deliveries, assisting with C-sections, performing lumbar punctures, performing and interpreting exercise tolerance tests, performing flexible sigmoidoscopies—no problem.

But the one thing that nearly always stopped me in my tracks was … you guessed it: dermatology complaints. Rashes, lesions, or any other skin complaint the least bit out of the ordinary were completely baffling to me. I still remember that feeling after all these years (and I still occasionally experience it!).

I felt like saying to those patients: What in the world would make you think I’d have any idea what that is? But of course, I couldn’t say that, so I’d mumble something, throw some cream at it, then quickly change the subject. Mind you, this was in a setting where a derm referral from us would take 4 to 6 months. And in case you’re wondering, the other providers in my department were as bad at derm as I was.

Long story short, it got to the point that I would scan my schedule every morning, praying I wouldn’t see the word “rash” or “skin.” But, of course, they still came—often just as my hand touched the doorknob to leave: “Oh, by the way, what about this …?” You get the picture. Many of you, if not most, live that picture.

I finally got up the nerve to go to our dermatology department to ask if I could follow one of the docs while he saw patients. Little did I know that practically every provider in the building had already done the same, and had been dismissed with words that essentially meant, “You? A mere PA? You can’t get there from here. Just send ’em to us.”

For a short time, I bought that line—but in the meantime, my patients were not getting the care they needed. So, driven in part by anger at the notion that a mere PA was simply unable to learn dermatology, I bought a decent textbook, Fitzpatrick’s Color Atlas of Dermatology, and started reading it. I also started collecting all the derm articles I could find in the journals, and read about those cases.

I won’t bore you with the grimy details, but what I did differently was work at learning derm (what a concept!). I started going to derm conferences, bought a good camera and started taking pictures with it, and continued to buy books (this was in the pre-computer days of the ’80s) and actually read them.

Continue to: And a funny thing happened...

And a funny thing happened: The more I read, the more diagnoses I recognized on my patients. My colleagues and the clinic schedulers took note of this and began sending me their problem cases. Even the derm department, beleaguered as usual by huge backlogs of patients, started sending patients to me. By 1985, even though I was in the internal medicine department, I had transitioned to doing derm fulltime. And that’s what I’ve been doing since.

Around 1992, I discovered that I was one of 6 dermatology PAs in this country. Last time I checked, our numbers were approaching 4,000. So, yes, derm is indeed difficult, but rocket science it isn’t.

Being the pedantic sort that I am, and finding that whole experience so enlightening, I resolved to make it my mission to foster the use of PAs in dermatology—part of which involves the education of those PAs, by means of taking students but also by writing articles (several hundred at last count) and lecturing at conferences and at PA programs. Nearing retirement, I only practice two days a week, but I write and publish at least 5 clinical articles a month, all of which are based on real cases: my cases, using my photos, doing new research on each case. This keeps my knowledge fresh and my 75-year-old mind sharp, helps ward off burnout, and, most importantly, saves lives while reducing patient discomfort.

What follows are 10 dermatology pearls that I have gleaned along the way. My apologies to my former students and attendees at my lectures who’ve heard all this before:

1 If the treatment for your diagnosis isn’t working, consider another diagnosis. Here’s an example (Figure 1): A man in his 50s was sent to dermatology for psoriasis that wasn’t responding to a biologic. Was it really psoriasis? A KOH prep quickly showed it to be tinea corporis, which cleared completely with a month’s worth of oral terbinafine (250 mg qid).

Continue to: #2...

2 The correct diagnosis dictates correct treatment. This may sound obvious, but in primary care, the emphasis is often on “let’s try this” or “let’s try that,” an understandable approach to a symptomatic patient with an uncertain diagnosis. But by the time he finally gets to dermatology, the patient has tried a whole bag full of prescription and OTC products given for numerous, totally different diagnoses. A better approach might be to expedite an urgent referral to dermatology, when possible.

3 Cutaneous fungal infections (ie, dermatophytosis) are vastly overdiagnosed, especially by novices. If you truly suspect it, ask about a potential source; one doesn’t acquire a fungal infection out of thin air. It must come from a person, animal, or occasionally, the soil. It also helps if the victim has been rendered susceptible by the injudicious use of steroids. Better yet, find the fungus with a microscopic examination (KOH prep) or culture. Finally, remember, not everything round and scaly is fungal (see Figure 2).

4 Remember these ancient words of wisdom regarding skin complaints: (a) A diagnosis is seldom made if not entertained, (b) you won’t entertain it if you’ve never heard of it, (c) you will not see it if you’re not looking for it, and (d) even if you did see it, you would not “see” it because you’re not looking for it. Dermatology is far deeper and wider than most imagine it to be. The trick is to expose yourself to as many different diagnoses as possible, by reading and attending lectures, ahead of the possible sighting. Figures 3 and 4 offer examples of common conditions that are seldom recognized outside dermatology.

5 Skin cancer can present as a rash. Examples abound, such as mammary and extramammary Paget’s disease (Figure 5), mycosis fungoides, metastatic breast cancer (Figure 6), and superficial basal cell carcinoma. A biopsy is usually required to diagnose these, but you wouldn’t think to do that if you’d never heard of the condition.

6 Melanoma doesn’t typically arise from a mole or other pre-existing lesion. Far more often, it arises “de novo,” out of nothing. So, in general, we’re not worried about “moles” (nevi) unless there’s a history of change (see Figure 7).

Continue to: #7...

7 When looking for skin cancer, pay as much attention to the owner as to the lesion. The most common skin cancers—basal cell and squamous cell carcinoma—usually occur on sun-damaged, fair-skinned, blue-eyed older patients. Though there are certainly exceptions to this paradigm, it pays to be generally suspicious of any odd lesion seen on these patients (Figure 8).

8 It’s practically impossible to overstate the role of atopy when evaluating pediatric skin complaints. These children—20% of all newborns!—are born with thin, dry, sensitive, overreactive skin that is prone to eczema and urticaria. They will also have a marked tendency to develop seasonal allergies, allergic rhinitis, and asthma. Parents find it difficult to accept the genetic basis for atopic dermatitis (Figure 9), preferring instead to blame everything on laundry detergent or food. Education (of oneself first!) is the key.

9 “Infections” are not always what they seem. These pearls may help: a) There are many causes of localized erythema, swelling, and tenderness that have nothing to do with infection. Examples include relapsing polychondritis (Figure 10) and cutaneous lupus (Figure 11). b) Skin cancer, such as basal cell carcinoma (see Figure 12), is often mistaken for infection. c) Some infections have less conventional or obvious sources; those caused by atypical mycobacteria (see Figure 13), leishmaniasis (see Figure 14), and sporothrix (see Figure 15), are good examples of this phenomenon. Consider thinking outside the box.

10 Overcome your fear of steroids by educating yourself about their safe use. Glucocorticoids (eg, triamcinolone, prednisone, betamethasone) are extremely useful in treating common derm conditions. We see patients every day who are so frightened of steroids, they won’t even consider using them because some well-meaning medical provider scared them to death. The proper use of these miraculous products could easily be the subject of an entire article. For now, I’ll advise you to read about their safe use in any number of dermatology texts (including online publications).

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

PARIS – A major worldwide survey of the 12-month prevalence of atopic dermatitis (AD) across the course of life provides new insights into global disease trends, Jonathan I. Silverberg, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Among the most important takeaways from this Internet-based survey of more than 273,645 infants, children, and adults in 18 countries across five continents conducted in 2017 was that “global atopic dermatitis prevalence appears to be higher in adults, at 10%, than in younger cohorts, where it’s 4%-8%, which I think is quite provocative and requires further study and confirmation,” said Dr. Silverberg, a dermatologist at Northwestern University in Chicago.

“Let’s keep in mind that there’s this accepted dogma in the literature than atopic dermatitis is somehow only a childhood disorder – it doesn’t affect adults. Well, these data tell a very different story because we’re actually seeing overall highest prevalences throughout the world occurring in adulthood,” based on the U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis (Br J Dermatol. 1994 Sep;131[3]:383-96).

This is the biggest epidemiologic survey ever to examine the 12-month prevalence and severity of AD around the world for both adults and children. Survey respondents included 172,627 adults aged 18 years and older, 34,212 adolescents aged 12-17 years, 54,806 children aged 2-11 years, and more than 12,000 infants.

Key findings from the study include the following:

• AD prevalence rates varied widely from country to country around the world, as well as by age groups (see graphic).
• The highest rate in adults was observed in China. South Korea had the highest rates in both children and adolescents. The top AD rates in infancy occurred in France and the United Kingdom.
• Rates across the age spectrum were consistently lowest in Israel and Switzerland.

“These kinds of patterns raise fascinating questions about the potential risk factors or protective factors that happen in different countries. There are some startling differences in terms of the different regions,” Dr. Silverberg observed. “Certain regions of the world really stand out as having much higher prevalences, particularly China and South Korea, and then as you get into the adult years, Brazil and Mexico, which I think are areas that, at least in the global atopic dermatitis epidemiology community, are not quite as well recognized as being hot spots for atopic dermatitis.”

Indeed, the 12-month prevalence rate of AD among adults was 14% in Mexico and 12% in Brazil, as compared with 13% in Saudi Arabia, 11% in Australia and Spain, 10% in Canada and the United Kingdom, and 9% in the United States.

The prevalence was generally lowest in infants, then jumped substantially within countries during the childhood years, declined slightly in adolescents, and then peaked in adulthood.

AD severity was assessed using PO-SCORAD, the Patient-Oriented Scoring AD measure. Most affected individuals had moderate AD as defined by a PO-SCORAD score of 25-50. Across the age spectrum, the highest proportion of infants with AD who had moderate disease was in China, with 72%. In Taiwan, 63% of children with AD had moderate disease, as did 68% of adolescents and an equal proportion of adults.

In the United Kingdom, 49% percent of infants with AD had severe disease, making that country the world leader in the youngest age group. Severe AD was most common among Turkish children, where 30% of kids with the skin disease had a PO-SCORAD score greater than 50. In Brazil, 31% of adolescents with AD had severe disease, the world’s highest rate in that age group. Among adults with AD, the world’s highest rate of severe disease was 25%, which was seen in the United States, Brazil, and Saudi Arabia.

Across the age spectrum, Japan had a consistently lower-end, overall, 12-month AD prevalence rate of 5%. Germany, Italy, and France had overall rates of 6%, 7%, and 8%, respectively. The rate was 9% in the United States and Canada, and it was 10% in Australia.

Dr. Silverberg performed validation analyses using the Patient-Oriented Eczema Measure (POEM) and diagnostic criteria similar to the earlier landmark International Study of Asthma and Allergies in Childhood, or ISAAC (Lancet. 1998 Apr 25;351[9111]:1225-32). This was a huge study that excluded the United States, leaving a hole in the epidemiologic picture of the disease that the new survey fills. The validation analyses were supportive of the main findings based on the U.K. Working Party criteria.

Dr. Silverberg reported serving as a consultant to Pfizer, which sponsored the global epidemiologic survey, as well as to roughly a dozen other pharmaceutical companies.

[email protected]

SOURCE: Silverberg JI. EADV Congress, Abstract FC01.01.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.

Patients with tumor necrosis factor inhibitor–induced psoriasis could potentially be switched to a different drug class if they have moderate to severe skin eruption or mild skin eruption with an uncontrolled underlying disease such as inflammatory bowel disease, psoriasis, psoriatic arthritis, or rheumatoid arthritis, according to a new treatment algorithm proposed by researchers from Brigham and Women’s Hospital and Harvard Medical School in Boston.

The researchers outlined the prevalence of tumor necrosis factor–alpha inhibitor (TNFi)-induced psoriasis in a literature review of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) and identified an estimated rate of between 2.3% and 5% in patients with RA and between 1.6% and 2.7% in patients with IBD. Although there have been reports of TNFi-induced psoriasis in patients with psoriasis and PsA, the prevalence is unclear, they wrote in the Journal of Psoriasis and Psoriatic Arthritis.

The authors then created an algorithm to manage and treat TNFi-induced psoriasiform skin eruptions with decisions to continue therapy and “treat through” symptoms, switch to a different anti-TNF therapy, or switch to a different drug class based on severity of symptoms, whether the underlying disease is well controlled, and how patients with those underlying diseases have fared with those specific therapies or agents.

“We’ve shifted gears over the past decade, and we’ve gone from having very few agents and trying to keep patients desperately on one or two agents because we didn’t want to have to give up on them for their other comorbid disease, whether it was Crohn’s, colitis, RA, or whatever it may be,” senior author Joseph Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, Boston, said in an interview. “We’re now in an area where we can have an algorithm like this, and we have so many more mechanistic options to move to.”

Dr. Merola, who is board certified in dermatology and rheumatology, said the algorithm is meant to “open a dialogue” with other specialists in different areas and raise awareness of treatments in related but separate fields. For diseases not often seen by more than one specialty, with the exception of psoriasis and PsA, he said that “the idea is to start a dialogue and increase communication between specialists.”

Dr. Merola noted that while the algorithm in many respects is meant to guide a physician in a specialty in appropriate medication decisions, at the same time he hopes that “it opens a dialogue and communication with the other specialty who tends to oversee this particular disease state or class of medicine to really work together to try to find the right drug for the right person.”

For patients with a mild skin eruption and a controlled underlying disease, the algorithm recommends a “treat through” approach by continuing anti-TNF therapy and treating psoriasis symptoms with topical steroids, ultraviolet therapy, methotrexate, cyclosporine, or acitretin, and to consider dapsone in cases of pustular psoriasis. However, the researchers noted that “treat through” studies have reported complete symptom resolution in 26%-41% of patients.

For patients with recalcitrant or worsening TNFi-induced psoriasis or patients with mild skin eruptions with an uncontrolled underlying disease, the researchers proposed considering switching to a different anti-TNF therapy, although studies have shown complete resolution of symptoms in only 5%-37% of patients.

If patients worsen from there, or if they have moderate to-severe skin eruption with uncontrolled underlying disease, they could be considered for switching to a different drug class and treated based on their underlying disease, along with treatment for psoriasis symptoms. This approach has been shown to completely resolve lesions in up to 64% of cases, they said. IBD patients could benefit from ustekinumab, vedolizumab, 6-mercaptopurine, or azathioprine as an alternative to anti-TNF therapy. Those patients with psoriasis should be considered for guselkumab, while ustekinumab, ixekizumab, secukinumab, and apremilast are effective treatments for patients with psoriasis and PsA. Patients with RA could receive treatment with tocilizumab, rituximab, abatacept, and tofacitinib, the authors wrote.

Dr. Merola reported serving as a consultant and/or investigator for Merck Research Laboratories, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GlaxoSmithKline, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma.

SOURCE: Li SJ et al. J Psoriasis Psoriatic Arthritis. 2018 Nov 21. doi: 10.1177/2475530318810851.