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Multiple atopic dermatitis therapies completed or close to completing phase 3 studies
Major , Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.
All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
Oral JAK inhibitors
The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.
“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.
Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.
“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.
Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.
Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.
The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.
Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.
Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.
“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.
Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.
All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.
“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.
Novel injectable biologics
Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.
Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.
But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).
“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.
It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.
Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.
“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.
Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
Nonsteroidal topical agents
These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.
These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Major , Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.
All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
Oral JAK inhibitors
The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.
“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.
Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.
“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.
Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.
Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.
The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.
Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.
Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.
“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.
Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.
All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.
“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.
Novel injectable biologics
Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.
Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.
But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).
“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.
It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.
Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.
“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.
Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
Nonsteroidal topical agents
These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.
These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Major , Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.
All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
Oral JAK inhibitors
The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.
“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.
Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.
“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.
Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.
Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.
The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.
Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.
Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.
“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.
Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.
All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.
“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.
Novel injectable biologics
Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.
Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.
But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).
“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.
It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.
Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.
“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.
Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
Nonsteroidal topical agents
These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.
These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Use of cannabinoids in dermatology here to stay
In the clinical opinion of .
“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”
In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.
“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.
According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.
In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.
Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”
Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.
Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”
Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”
The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.
In the clinical opinion of .
“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”
In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.
“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.
According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.
In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.
Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”
Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.
Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”
Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”
The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.
In the clinical opinion of .
“There’s no question in my mind about that. Don’t play catch-up; be at the forefront, because at a minimum your patients are going to ask you about this,” he said in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
In 2018, officials at Health Canada reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids and published a free downloadable guide for health care professionals. “In the book, dermatology doesn’t have its own section,” said Dr. Friedman, professor and interim chair of dermatology at George Washington University, Washington. “It falls under inflammation and makes up four paragraphs of the entire book, which is weird, given that if you survey the dispensaries in Canada, the majority of them led in with dermatologic indications, many of which are completely unsubstantiated.”
In the United States, a recent survey of 531 dermatologists led by Elizabeth S. Robinson, MD, of George Washington University, found that 55% reported at least one patient-initiated discussion about cannabinoids in the last year (J Drugs Dermatol. 2018;17[2]:1273-8). However, 48% were concerned about a negative stigma when proposing cannabinoid therapies to patients. While most respondents (86%) were willing to prescribe an FDA-approved cannabinoid as a topical treatment, fewer (71%) were willing to prescribe an oral form. In an unpublished study conducted 2 years later, 155 dermatologists were asked if they had ever recommended medical cannabis products for the treatment/management of a dermatologic condition. More than 80% said they had not.
“It’s important to recognize that if we have a strong fund of knowledge, we can guide these patients to use the right cannabinoids for the right indications, so long as we have some evidence supporting it,” said Dr. Friedman, residency program director and director of translational research in George Washington University’s department of dermatology.
According to existing medical literature, cannabinoids may ultimately play a role in the treatment of eczema (J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2020.01.036 and ClinicalTrials.gov NCT03824405), psoriasis, acne, and certain collagen vascular diseases, including scleroderma, dermatomyositis, and cutaneous lupus erythematosus (CLE). Most of the evidence for its use in collagen vascular diseases comes from the investigation of a synthetic cannabinoid known as anabasum, which is derived from TCH, but it has no affinity for the CB1 receptor. “Rather, it goes after the CB2 receptor, which is heavily prevalent in the immune system,” he noted.
In the summer of 2018, the FDA granted Orphan Drug Designation to Corbus Pharmaceuticals for lenabasum, a derivative of anabasum, for the treatment of dermatomyositis. “Hopefully, we’ll see this in the next year,” said Dr. Friedman, who consults for Corbus. A more recent study showed that lenabasum could reduce the production of interleukin-31 (Br. J Dermatol 2018;179[3]:669-78), which “I think will have broader implications in dermatology beyond dermatomyositis,” he said.
Dr. Friedman also reviewed data on a topical endocannabinoid nanoparticle-based formulation his team developed and is studying for the treatment of CLE. “There is a huge unmet need as there are no topical therapies approved for CLE,” he said. “Our animal data are very promising and we plan to move forward to human studies shortly.”
Resources for clinicians to improve their understanding about the potential use of cannabinoids in dermatology include an online certificate program in cannabis medicine offered by Thomas Jefferson University, as well as their state departments of health. Other resources include the International Cannabinoid Research Society, the International Association for Cannabinoid Medicines, the University of California’s Center for Medicinal Cannabis Research, and the Canadian Consortium for the Investigation of Cannabinoids.
Dr. Friedman noted that marijuana may exacerbate appetite, sleepiness, dizziness, low blood pressure, dry mouth/eyes, decreased urination, hallucinations, paranoia, anxiety, poor balance and posture in patients with dyskinetic disorders, and impaired attention, memory, and psychomotor performance. High concentrations can cause hyperemesis syndrome and exacerbate existing psychoses. With respect to cannabidiol (CBD), “unless you go with super high concentrations, over 50 mg/kg per day, you’re probably not going to run into so much trouble,” Dr. Friedman said. “Above that, you do get some liver function test abnormalities. The problem is, a lot of CBD-based products have impurities in them.”
Different state-based requirements exist for recommending cannabinoid products to your patients “so it’s important to know those requirements,” Dr. Friedman said. “I have patients sign a cannabis contrast. There are examples of these online. My mantra is start low and go slow, and stay low as much as possible.”
The virtual meeting at George Washington University included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Friedman reported that he serves as a consultant and/or adviser to numerous pharmaceutical companies, including some that produce cannabinoids. He is a speaker for Regeneron/Sanofi, Abbvie, and Dermira, and has received grants from Pfizer and the Dermatology Foundation.
A case of neutrophilic eccrine hidradenitis attributed to HIV treatment
arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.
The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.
Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.
The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.
The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.
Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.
Dr. Kalen reported having no financial conflicts regarding her presentation.
arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.
The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.
Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.
The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.
The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.
Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.
Dr. Kalen reported having no financial conflicts regarding her presentation.
arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.
The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.
Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.
The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.
The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.
Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.
Dr. Kalen reported having no financial conflicts regarding her presentation.
Expert discusses her approach to using systemic agents in children and adolescents with severe skin disease
In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.
“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”
Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.
. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”
Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”
Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”
When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.
Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.
Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”
In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”
GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”
Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”
When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”
Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”
Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”
The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”
Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”
Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.
In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.
“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”
Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.
. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”
Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”
Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”
When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.
Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.
Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”
In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”
GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”
Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”
When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”
Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”
Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”
The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”
Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”
Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.
In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.
“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”
Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.
. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”
Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”
Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”
When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.
Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.
Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”
In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”
GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”
Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”
When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”
Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”
Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”
The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”
Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”
Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.
When to suspect calciphylaxis and what to do about it
If the shoe fits a presumptive clinical diagnosis of calciphylaxis, wear it – and don’t assume that ordering imaging studies or histology will make for a better fit or is even necessary.
That was the key message of Karl M. Saardi, MD, during his video presentation at a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
“ said Dr. Saardi, a dermatology resident at Georgetown University in Washington, D.C.
He presented a single-center, retrospective study that underscored the diagnostic challenges posed by calciphylaxis, a condition for which there are no generally accepted clinical, radiographic, or histologic diagnostic criteria.
The rare skin condition is characterized by calcium deposition in small arterioles and capillaries in the skin and subcutaneous tissue. It’s most common in patients with end-stage renal disease who are on dialysis; however, there is also an increasingly recognized nonuremic variant that’s associated with the use of warfarin, chronic steroids, obesity, and possibly with being antiphospholipid antibody positive.
Calciphylaxis is an extremely painful condition – the pain is ischemic in nature – and it’s associated with substantial morbidity as well as a mortality rate that in many series exceeds 50%. Affected individuals typically present with progressive, painful retiform purpura on the legs, belly, buttocks, and other fatty body sites.
Dr. Saardi’s study entailed a retrospective look at the medical records and pathologic reports of 57 patients who underwent skin biopsy for suspected calciphylaxis. Of the 57, 18 had no antecedent imaging studies done during the preceding 3 months; 8 of those 18 (40%), had a confirmatory positive biopsy. A total of 39 patients did have imaging studies, deemed positive for calciphylaxis in 11 cases, which in only 5 of the 11 imaging-positive cases (45%) were subsequently confirmed by positive biopsy.
And finally, of the 28 patients with negative imaging studies, 10 (36%), had a positive biopsy. Those positive biopsy rates, ranging from 36% to 45%, did not differ statistically. Thus, whether an imaging study was positive or negative, or wasn’t even done, made no difference in terms of the ultimate diagnosis.
“You may not need imaging studies, because imaging has often been done before the consultation is requested because people are looking for things like arterial thrombus, cellulitis, [deep vein thrombosis] or something like that,” Dr. Saardi noted. “In our series, the indication was never calciphylaxis, it was always something like pain, infection, swelling, suspected [deep vein thrombosis], things like that.”
The classic signature of calciphylaxis on plain x-ray is net-like calcifications in skin and subcutaneous tissue. In one study, this often-subtle finding was associated with a 830% increased likelihood of a positive biopsy, with a specificity of 90%; however, these x-ray changes were only found in 13 of 29 patients with biopsy-confirmed calciphylaxis.
“It’s really important when you request plain films in these patients to review the images yourself or together with the radiologist because oftentimes the indication for imaging will be very different from what we’re looking for. Radiologists often won’t know to look for this specifically,” Dr. Saardi said.
The classic histopathologic finding is calcification of the small- and medium-sized vessels in the dermis and subcutaneous soft tissue. However, sometimes all that’s present are small intravascular inflammatory thrombi with intimal hyperplasia.
Skin biopsies are not infrequently falsely negative or nondiagnostic. To maximize the utility of the procedure, it’s important to go deep and gather a tissue sample that extends into subcutaneous tissue.
“You need to do a very deep punch or double-punch biopsy,” he said. “Another key is to avoid biopsy if the pretest probability of calciphylaxis is high because a negative biopsy shouldn’t necessarily reassure you or cause you to withhold treatment. And with the concern about pathergy or Koebnerization of the area causing a wound that’s never going to heal, sometimes a biopsy is not needed if the pretest suspicion is high enough.”
Other investigators have shown that the likelihood of an informative biopsy is enhanced by using a calcium stain on the specimen and having an experienced dermatopathologist do the evaluation. Also, the use of a radiographically guided core needle biopsy to ensure that the physician is getting sufficiently deep into subcutaneous fat is now under evaluation.
In addition to plain radiographs, other imaging methods that are sometimes used to evaluate soft-tissue sites for suspected calciphylaxis included CT and ultrasound. Dr. Saardi is particularly intrigued by reports from investigators at Harvard University regarding the utility of nuclear bone scintigraphy; in one study, this form of imaging was positive in 16 of 18 patients with clinically diagnosed calciphylaxis, versus just 1 of 31 controls with end-stage renal disease.
“We’ve started doing this in situations where biopsy is not desirable or feasible at that moment,” he said.
Dr. Saardi reported having no financial conflicts regarding his presentation.
If the shoe fits a presumptive clinical diagnosis of calciphylaxis, wear it – and don’t assume that ordering imaging studies or histology will make for a better fit or is even necessary.
That was the key message of Karl M. Saardi, MD, during his video presentation at a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
“ said Dr. Saardi, a dermatology resident at Georgetown University in Washington, D.C.
He presented a single-center, retrospective study that underscored the diagnostic challenges posed by calciphylaxis, a condition for which there are no generally accepted clinical, radiographic, or histologic diagnostic criteria.
The rare skin condition is characterized by calcium deposition in small arterioles and capillaries in the skin and subcutaneous tissue. It’s most common in patients with end-stage renal disease who are on dialysis; however, there is also an increasingly recognized nonuremic variant that’s associated with the use of warfarin, chronic steroids, obesity, and possibly with being antiphospholipid antibody positive.
Calciphylaxis is an extremely painful condition – the pain is ischemic in nature – and it’s associated with substantial morbidity as well as a mortality rate that in many series exceeds 50%. Affected individuals typically present with progressive, painful retiform purpura on the legs, belly, buttocks, and other fatty body sites.
Dr. Saardi’s study entailed a retrospective look at the medical records and pathologic reports of 57 patients who underwent skin biopsy for suspected calciphylaxis. Of the 57, 18 had no antecedent imaging studies done during the preceding 3 months; 8 of those 18 (40%), had a confirmatory positive biopsy. A total of 39 patients did have imaging studies, deemed positive for calciphylaxis in 11 cases, which in only 5 of the 11 imaging-positive cases (45%) were subsequently confirmed by positive biopsy.
And finally, of the 28 patients with negative imaging studies, 10 (36%), had a positive biopsy. Those positive biopsy rates, ranging from 36% to 45%, did not differ statistically. Thus, whether an imaging study was positive or negative, or wasn’t even done, made no difference in terms of the ultimate diagnosis.
“You may not need imaging studies, because imaging has often been done before the consultation is requested because people are looking for things like arterial thrombus, cellulitis, [deep vein thrombosis] or something like that,” Dr. Saardi noted. “In our series, the indication was never calciphylaxis, it was always something like pain, infection, swelling, suspected [deep vein thrombosis], things like that.”
The classic signature of calciphylaxis on plain x-ray is net-like calcifications in skin and subcutaneous tissue. In one study, this often-subtle finding was associated with a 830% increased likelihood of a positive biopsy, with a specificity of 90%; however, these x-ray changes were only found in 13 of 29 patients with biopsy-confirmed calciphylaxis.
“It’s really important when you request plain films in these patients to review the images yourself or together with the radiologist because oftentimes the indication for imaging will be very different from what we’re looking for. Radiologists often won’t know to look for this specifically,” Dr. Saardi said.
The classic histopathologic finding is calcification of the small- and medium-sized vessels in the dermis and subcutaneous soft tissue. However, sometimes all that’s present are small intravascular inflammatory thrombi with intimal hyperplasia.
Skin biopsies are not infrequently falsely negative or nondiagnostic. To maximize the utility of the procedure, it’s important to go deep and gather a tissue sample that extends into subcutaneous tissue.
“You need to do a very deep punch or double-punch biopsy,” he said. “Another key is to avoid biopsy if the pretest probability of calciphylaxis is high because a negative biopsy shouldn’t necessarily reassure you or cause you to withhold treatment. And with the concern about pathergy or Koebnerization of the area causing a wound that’s never going to heal, sometimes a biopsy is not needed if the pretest suspicion is high enough.”
Other investigators have shown that the likelihood of an informative biopsy is enhanced by using a calcium stain on the specimen and having an experienced dermatopathologist do the evaluation. Also, the use of a radiographically guided core needle biopsy to ensure that the physician is getting sufficiently deep into subcutaneous fat is now under evaluation.
In addition to plain radiographs, other imaging methods that are sometimes used to evaluate soft-tissue sites for suspected calciphylaxis included CT and ultrasound. Dr. Saardi is particularly intrigued by reports from investigators at Harvard University regarding the utility of nuclear bone scintigraphy; in one study, this form of imaging was positive in 16 of 18 patients with clinically diagnosed calciphylaxis, versus just 1 of 31 controls with end-stage renal disease.
“We’ve started doing this in situations where biopsy is not desirable or feasible at that moment,” he said.
Dr. Saardi reported having no financial conflicts regarding his presentation.
If the shoe fits a presumptive clinical diagnosis of calciphylaxis, wear it – and don’t assume that ordering imaging studies or histology will make for a better fit or is even necessary.
That was the key message of Karl M. Saardi, MD, during his video presentation at a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
“ said Dr. Saardi, a dermatology resident at Georgetown University in Washington, D.C.
He presented a single-center, retrospective study that underscored the diagnostic challenges posed by calciphylaxis, a condition for which there are no generally accepted clinical, radiographic, or histologic diagnostic criteria.
The rare skin condition is characterized by calcium deposition in small arterioles and capillaries in the skin and subcutaneous tissue. It’s most common in patients with end-stage renal disease who are on dialysis; however, there is also an increasingly recognized nonuremic variant that’s associated with the use of warfarin, chronic steroids, obesity, and possibly with being antiphospholipid antibody positive.
Calciphylaxis is an extremely painful condition – the pain is ischemic in nature – and it’s associated with substantial morbidity as well as a mortality rate that in many series exceeds 50%. Affected individuals typically present with progressive, painful retiform purpura on the legs, belly, buttocks, and other fatty body sites.
Dr. Saardi’s study entailed a retrospective look at the medical records and pathologic reports of 57 patients who underwent skin biopsy for suspected calciphylaxis. Of the 57, 18 had no antecedent imaging studies done during the preceding 3 months; 8 of those 18 (40%), had a confirmatory positive biopsy. A total of 39 patients did have imaging studies, deemed positive for calciphylaxis in 11 cases, which in only 5 of the 11 imaging-positive cases (45%) were subsequently confirmed by positive biopsy.
And finally, of the 28 patients with negative imaging studies, 10 (36%), had a positive biopsy. Those positive biopsy rates, ranging from 36% to 45%, did not differ statistically. Thus, whether an imaging study was positive or negative, or wasn’t even done, made no difference in terms of the ultimate diagnosis.
“You may not need imaging studies, because imaging has often been done before the consultation is requested because people are looking for things like arterial thrombus, cellulitis, [deep vein thrombosis] or something like that,” Dr. Saardi noted. “In our series, the indication was never calciphylaxis, it was always something like pain, infection, swelling, suspected [deep vein thrombosis], things like that.”
The classic signature of calciphylaxis on plain x-ray is net-like calcifications in skin and subcutaneous tissue. In one study, this often-subtle finding was associated with a 830% increased likelihood of a positive biopsy, with a specificity of 90%; however, these x-ray changes were only found in 13 of 29 patients with biopsy-confirmed calciphylaxis.
“It’s really important when you request plain films in these patients to review the images yourself or together with the radiologist because oftentimes the indication for imaging will be very different from what we’re looking for. Radiologists often won’t know to look for this specifically,” Dr. Saardi said.
The classic histopathologic finding is calcification of the small- and medium-sized vessels in the dermis and subcutaneous soft tissue. However, sometimes all that’s present are small intravascular inflammatory thrombi with intimal hyperplasia.
Skin biopsies are not infrequently falsely negative or nondiagnostic. To maximize the utility of the procedure, it’s important to go deep and gather a tissue sample that extends into subcutaneous tissue.
“You need to do a very deep punch or double-punch biopsy,” he said. “Another key is to avoid biopsy if the pretest probability of calciphylaxis is high because a negative biopsy shouldn’t necessarily reassure you or cause you to withhold treatment. And with the concern about pathergy or Koebnerization of the area causing a wound that’s never going to heal, sometimes a biopsy is not needed if the pretest suspicion is high enough.”
Other investigators have shown that the likelihood of an informative biopsy is enhanced by using a calcium stain on the specimen and having an experienced dermatopathologist do the evaluation. Also, the use of a radiographically guided core needle biopsy to ensure that the physician is getting sufficiently deep into subcutaneous fat is now under evaluation.
In addition to plain radiographs, other imaging methods that are sometimes used to evaluate soft-tissue sites for suspected calciphylaxis included CT and ultrasound. Dr. Saardi is particularly intrigued by reports from investigators at Harvard University regarding the utility of nuclear bone scintigraphy; in one study, this form of imaging was positive in 16 of 18 patients with clinically diagnosed calciphylaxis, versus just 1 of 31 controls with end-stage renal disease.
“We’ve started doing this in situations where biopsy is not desirable or feasible at that moment,” he said.
Dr. Saardi reported having no financial conflicts regarding his presentation.
D.C.-area blacks face increased risk of mortality from SJS/TEN
(TEN), compared with nonblack patients, results from a single-center study showed.
Adam Swigost, MD, presented data on behalf of the study’s principal investigator, Helena B. Pasieka, MD, and associates at MedStar Health Georgetown University in Washington in a video presentation during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
According to the 2009-2012 Nationwide Inpatient Survey, there were 12,195 cases of SJS, 2,373 cases of SJS/TEN overlap, and 2,675 cases of TEN. In 2016, researchers led by Derek Y. Hsu, MD, of Northwestern University, Chicago, found that SJS/TEN was associated with nonwhite race, particularly Asians (odds ratio, 3.27) and blacks (OR, 2.01) (J Invest Dermatol. 2016;136[7]:1387-97).
“This led Dr. Pasieka and our team to ask the question: Are there differences in SJS/TEN outcomes in self-reported blacks in the U.S.?” said Dr. Swigost, a resident in the department of dermatology at MedStar Health Georgetown University.
To find out, he and his colleagues retrospectively analyzed records from 74 patients with SJS/TEN who were treated at Washington Hospital Center in Washington, D.C., from 2009 to 2019. They drew data from clinical diagnoses with histopathologic evaluation, when available, and performed a multivariate analysis adjusted for age, HIV status, black race, and offending drug category.
Of the 75 patients, 43 were female, 45 were black, 16 were white, 6 were Asian, 5 were Indian, 1 was Native American, and 1 was South Asian. Multivariate analysis revealed that black race was the only significant variable associated with an elevated risk of mortality from SJS/TEN (OR, 4.81; P = .04).
Of the 45 black patients in the study, 33 were HIV negative and 12 were HIV positive. “While this variable was not statistically significant, it did seem to have an elevated risk for mortality in HIV-positive patients [4 of 12; 33%], compared with 8 of 33 HIV-negative patients [25%],” Dr. Swigost said.
Next, the researchers investigated the culprit medications in the black patients. As a reference, they compared their data with a 2015 study that set out to document the clinical profile, etiologies, and outcomes of SJS and TEN in hospitals in four sub-Saharan African countries (Int J Dermatol. 2013 May;52[5]:575-9). In the 2015 study, sulfonamides were the most-used drugs (38%) followed by the antiretroviral drug nevirapine (20%) and tuberculosis drugs (6%). In the study by Dr. Swigost and colleagues, the most frequently implicated drugs were sulfonamides (24%), followed by other antibiotics (24%), and anticonvulsants (17%).
“Our patients at MedStar Washington Hospital Center are going to have different comorbidities and medical problems that dictate different medications being used in different proportions,” Dr. Swigost explained.
Delayed detection is one possible reason for the increased mortality observed in black patients. “Dermatology education on a national level is biased most commonly toward white skin,” he said. “Often, diseases can be missed in skin of color. It’s possible that the diagnoses are being delayed and so treatment is being delayed.”
Socioeconomics and access to health care could also play a role in the poor outcome we observed. “Those are variables we want to further analyze in this data,” Dr. Swigost said. “Other things to consider are genetic variations between African and American black patient populations, because in the U.S. our black population is likely more heterogeneous than African patient populations are. It’s possible that there are HLA [human leukocyte antigen] differences that are contributing. Lastly, further characterization and stratification of SJS/TEN risk factors are required.”
Dr. Swigost and Dr. Pasieka reported having no disclosures.
(TEN), compared with nonblack patients, results from a single-center study showed.
Adam Swigost, MD, presented data on behalf of the study’s principal investigator, Helena B. Pasieka, MD, and associates at MedStar Health Georgetown University in Washington in a video presentation during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
According to the 2009-2012 Nationwide Inpatient Survey, there were 12,195 cases of SJS, 2,373 cases of SJS/TEN overlap, and 2,675 cases of TEN. In 2016, researchers led by Derek Y. Hsu, MD, of Northwestern University, Chicago, found that SJS/TEN was associated with nonwhite race, particularly Asians (odds ratio, 3.27) and blacks (OR, 2.01) (J Invest Dermatol. 2016;136[7]:1387-97).
“This led Dr. Pasieka and our team to ask the question: Are there differences in SJS/TEN outcomes in self-reported blacks in the U.S.?” said Dr. Swigost, a resident in the department of dermatology at MedStar Health Georgetown University.
To find out, he and his colleagues retrospectively analyzed records from 74 patients with SJS/TEN who were treated at Washington Hospital Center in Washington, D.C., from 2009 to 2019. They drew data from clinical diagnoses with histopathologic evaluation, when available, and performed a multivariate analysis adjusted for age, HIV status, black race, and offending drug category.
Of the 75 patients, 43 were female, 45 were black, 16 were white, 6 were Asian, 5 were Indian, 1 was Native American, and 1 was South Asian. Multivariate analysis revealed that black race was the only significant variable associated with an elevated risk of mortality from SJS/TEN (OR, 4.81; P = .04).
Of the 45 black patients in the study, 33 were HIV negative and 12 were HIV positive. “While this variable was not statistically significant, it did seem to have an elevated risk for mortality in HIV-positive patients [4 of 12; 33%], compared with 8 of 33 HIV-negative patients [25%],” Dr. Swigost said.
Next, the researchers investigated the culprit medications in the black patients. As a reference, they compared their data with a 2015 study that set out to document the clinical profile, etiologies, and outcomes of SJS and TEN in hospitals in four sub-Saharan African countries (Int J Dermatol. 2013 May;52[5]:575-9). In the 2015 study, sulfonamides were the most-used drugs (38%) followed by the antiretroviral drug nevirapine (20%) and tuberculosis drugs (6%). In the study by Dr. Swigost and colleagues, the most frequently implicated drugs were sulfonamides (24%), followed by other antibiotics (24%), and anticonvulsants (17%).
“Our patients at MedStar Washington Hospital Center are going to have different comorbidities and medical problems that dictate different medications being used in different proportions,” Dr. Swigost explained.
Delayed detection is one possible reason for the increased mortality observed in black patients. “Dermatology education on a national level is biased most commonly toward white skin,” he said. “Often, diseases can be missed in skin of color. It’s possible that the diagnoses are being delayed and so treatment is being delayed.”
Socioeconomics and access to health care could also play a role in the poor outcome we observed. “Those are variables we want to further analyze in this data,” Dr. Swigost said. “Other things to consider are genetic variations between African and American black patient populations, because in the U.S. our black population is likely more heterogeneous than African patient populations are. It’s possible that there are HLA [human leukocyte antigen] differences that are contributing. Lastly, further characterization and stratification of SJS/TEN risk factors are required.”
Dr. Swigost and Dr. Pasieka reported having no disclosures.
(TEN), compared with nonblack patients, results from a single-center study showed.
Adam Swigost, MD, presented data on behalf of the study’s principal investigator, Helena B. Pasieka, MD, and associates at MedStar Health Georgetown University in Washington in a video presentation during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
According to the 2009-2012 Nationwide Inpatient Survey, there were 12,195 cases of SJS, 2,373 cases of SJS/TEN overlap, and 2,675 cases of TEN. In 2016, researchers led by Derek Y. Hsu, MD, of Northwestern University, Chicago, found that SJS/TEN was associated with nonwhite race, particularly Asians (odds ratio, 3.27) and blacks (OR, 2.01) (J Invest Dermatol. 2016;136[7]:1387-97).
“This led Dr. Pasieka and our team to ask the question: Are there differences in SJS/TEN outcomes in self-reported blacks in the U.S.?” said Dr. Swigost, a resident in the department of dermatology at MedStar Health Georgetown University.
To find out, he and his colleagues retrospectively analyzed records from 74 patients with SJS/TEN who were treated at Washington Hospital Center in Washington, D.C., from 2009 to 2019. They drew data from clinical diagnoses with histopathologic evaluation, when available, and performed a multivariate analysis adjusted for age, HIV status, black race, and offending drug category.
Of the 75 patients, 43 were female, 45 were black, 16 were white, 6 were Asian, 5 were Indian, 1 was Native American, and 1 was South Asian. Multivariate analysis revealed that black race was the only significant variable associated with an elevated risk of mortality from SJS/TEN (OR, 4.81; P = .04).
Of the 45 black patients in the study, 33 were HIV negative and 12 were HIV positive. “While this variable was not statistically significant, it did seem to have an elevated risk for mortality in HIV-positive patients [4 of 12; 33%], compared with 8 of 33 HIV-negative patients [25%],” Dr. Swigost said.
Next, the researchers investigated the culprit medications in the black patients. As a reference, they compared their data with a 2015 study that set out to document the clinical profile, etiologies, and outcomes of SJS and TEN in hospitals in four sub-Saharan African countries (Int J Dermatol. 2013 May;52[5]:575-9). In the 2015 study, sulfonamides were the most-used drugs (38%) followed by the antiretroviral drug nevirapine (20%) and tuberculosis drugs (6%). In the study by Dr. Swigost and colleagues, the most frequently implicated drugs were sulfonamides (24%), followed by other antibiotics (24%), and anticonvulsants (17%).
“Our patients at MedStar Washington Hospital Center are going to have different comorbidities and medical problems that dictate different medications being used in different proportions,” Dr. Swigost explained.
Delayed detection is one possible reason for the increased mortality observed in black patients. “Dermatology education on a national level is biased most commonly toward white skin,” he said. “Often, diseases can be missed in skin of color. It’s possible that the diagnoses are being delayed and so treatment is being delayed.”
Socioeconomics and access to health care could also play a role in the poor outcome we observed. “Those are variables we want to further analyze in this data,” Dr. Swigost said. “Other things to consider are genetic variations between African and American black patient populations, because in the U.S. our black population is likely more heterogeneous than African patient populations are. It’s possible that there are HLA [human leukocyte antigen] differences that are contributing. Lastly, further characterization and stratification of SJS/TEN risk factors are required.”
Dr. Swigost and Dr. Pasieka reported having no disclosures.
Routinely screen for depression in atopic dermatitis
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Jonathan I. Silverberg, MD, PhD, declared in a video presentation during a virtual meeting held by the George Washington University department of dermatology.
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.
Dr. Silverberg presented highlights of his recent study of depression screening rates in the National Ambulatory Medical Care Survey, an annual population-based survey by the National Center for Health Statistics. He and his coinvestigator analyzed 9,345 office visits for atopic dermatitis (AD) and 2,085 for psoriasis (Br J Dermatol. 2019 Oct 24. doi: 10.1111/bjd.18629.). The picture that emerged showed that there is much room for improvement.
“We found that depression screening rates were abysmally low in atopic dermatitis patients, with less than 2% patients being screened. There was very little difference in screening rates between patients on an advanced therapy, like systemic phototherapy or a biologic, compared to those who were just on topical therapy alone, meaning even the more severe patients aren’t being asked these questions. And no difference between dermatologists and primary care physicians,” said Dr. Silverberg, director of clinical research and contact dermatitis in the department of dermatology at George Washington University, Washington.
For Dr. Silverberg, known for his pioneering work documenting the marked yet often-underappreciated negative impact of AD on quality of life and mental health, these rock-bottom screening rates were particularly galling.
“There are very high rates of anxiety and depression amongst our patients with atopic dermatitis,” the dermatologist emphasized. “Mental health symptoms are an incredibly important domain in atopic dermatitis that we need to ask our patients about. We don’t ask enough.
“This to me is actually a very important symptom to measure. It’s not just a theoretical construct involved in understanding the burden of the disease, it’s something that’s actionable because most of these cases of mental health symptoms are reversible or modifiable with improved control of the atopic dermatitis,” he continued. “I use this as an indication to step up therapy. If a patient is clinically depressed and we believe that’s secondary to their chronic atopic dermatitis, this is a reason to step up therapy to something stronger.”
If the depressive symptoms don’t improve after stepping up the intensity of the dermatologic therapy, it’s probably time for the patient to see a mental health professional, Dr. Silverberg advised, adding, “I’m not telling every dermatology resident out there to become a psychiatrist.”
Depression and anxiety in AD: How common?
In an analysis of multiyear data from the Medical Expenditure Panel Surveys, an annual population-based project conducted by the Agency for Healthcare Research and Quality, Dr. Silverberg and a coinvestigator found that adults with AD were an adjusted 186% more likely than those without AD to screen positive for depressive symptoms on the two-item Patient Health Questionnaire (PHQ-2), with rates of 44.3% and 21.9%, respectively. The AD patients were also 500% more likely to screen positive for severe psychological distress, with a 25.9% rate of having a Kessler-6 index score of 13 or more, compared with 5.5% in adults without AD.
The rate of severe psychological distress was higher in adults with AD than in those with asthma, diabetes, hypertension, urticaria, or psoriasis, and was comparable with the rate in individuals with autoimmune disease (Ann Allergy Asthma Immunol. 2019 Aug;123[2]:179-85).
“It’s surprising when you think that the majority of the cases of atopic dermatitis in the population are mild and yet when you look at a population-based sample such as this you see a strong signal come up. It means that, with all the dilution of mild disease, the signal is still there. It emphasizes that even patients with mild disease get these depressive symptoms and psychosocial distress,” Dr. Silverberg observed.
In a separate analysis of the same national database, this time looking at Short Form-6D health utility scores – a measure of overall quality of life encompassing key domains including vitality, physical function, mental health, fatigue – adults with AD scored markedly worse than individuals with no chronic health disorders. Health utility scores were particularly low in adults with AD and comorbid symptoms of anxiety or depression, suggesting that those affective symptoms are major drivers of the demonstrably poor quality of life in adult AD (Ann Allergy Asthma Immunol. 2020 Jan;124[1]:88-9).
In the Atopic Dermatitis in America Study, Dr. Silverberg and coinvestigators cross-sectionally surveyed 2,893 adults using the seven-item Hospital Anxiety and Depression Scale anxiety (HADS-A) and depression (HADS-D) assessment instruments. Individuals with AD as determined using the modified U.K. Diagnostic Criteria had dramatically higher rates of both depression and anxiety. For example, the prevalence of a HADS-A score of 11 or more, which is considered to be case finding for clinically important anxiety, was 28.6% in adults with AD, nearly twice the 15.5% prevalence in those without the dermatologic disease. A HADS-D score of 11 or greater was present in 13.5% of subjects with AD and 9% of those without.
HADS-A and -D scores were higher in adults with moderate AD, compared with mild disease, and higher still in those with severe AD. Indeed, virtually all individuals with moderate to severe AD had symptoms of anxiety and depression, which in a large proportion had gone undiagnosed. A multivariate analysis strongly suggested that AD severity was the major driver of anxiety and depression in adults with AD (Br J Dermatol. 2019 Sep;181[3]:554-65).
An important finding was that 100% of adults with AD who had scores in the severe range on three validated measures of itch, frequency of symptoms, and lesion severity had borderline or abnormal scores on the HADS-A and -D.
“Of course, if you don’t ask, you’re not going to know about it,” Dr. Silverberg noted.
Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.
Low-income DC communities have restricted access to iPLEDGE pharmacies
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Residents of , results from a survey demonstrated.
Prescription of isotretinoin is regulated by the iPLEDGE program, which strives to ensure that no female patient starts isotretinoin therapy if pregnant and that no female patient on isotretinoin therapy becomes pregnant. “Over the years, many studies have criticized the program by demonstrating that iPLEDGE has promoted health care disparities,” Nidhi Shah said during a virtual meeting held by the George Washington University department of dermatology. “For example, racial minorities and women are more likely to be underprescribed isotretinoin, as well as face more delays in treatment.”
In an effort to evaluate the geographic distribution of iPLEDGE pharmacies in Washington DC, and its correlation with sociodemographic factors, Ms. Shah, a third-year medical student at the George Washington University, Washington, and colleagues obtained a list of active pharmacies in Washington from the local government. They also surveyed each outpatient pharmacy in the District of Columbia to verify their iPLEDGE registration status, for a total of 146 pharmacies.
Ms. Shah reported that 82% of all outpatient pharmacies were enrolled in iPLEDGE. However, enrollment significantly varied by the type of pharmacy. For example, 100% of chain pharmacies were enrolled, compared with 46% of independent pharmacies and 60% of hospital-based pharmacies.
When the researchers evaluated the number and type of iPLEDGE pharmacy by each of the eight wards in Washington, they observed a high density of pharmacies in wards 1 and 2, communities with a generally low proportion of residents who live in poverty, and low density of pharmacies in wards 7 and 8, communities with a higher proportion of residents who live in poverty. In addition, there were more independent than chain pharmacies in wards 7 and 8, and residents in those wards had a greater distance to travel to reach an iPLEDGE pharmacy, compared with residents who live in the other wards.
When Ms. Shah and colleagues examined the correlation between pharmacies per 10,000 residents and specific sociodemographic factors, they observed a strong, positive correlation between iPLEDGE pharmacy density and median household income (P = .0003). On the other hand, there was a strong negative correlation between iPLEDGE pharmacy density and the percentage of individuals with public insurance (P less than .0001), as well as the percentage of nonwhite individuals (P = .0009).
“Our study highlights the lack of isotretinoin-dispensing pharmacies in low-income communities,” Ms. Shah concluded. “Not only are there fewer such pharmacies available in low income communities, but the residents must also travel further to reach them. The spatial heterogeneity of iPLEDGE pharmacies may be an important patient barrier to timely access of isotretinoin, especially for female patients who have a strict 7-day window to collect their medication. We hope that future public health reform works to close this gap.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Ms. Shah reported having no disclosures.
Study finds spironolactone doesn’t boost breast cancer recurrence
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
Survey explores the role of social media in choosing a dermatologist
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.