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Topical roflumilast approved for psoriasis in adults and adolescents
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Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.
In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.
FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.
At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).
Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).
In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).
In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.
In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.
“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.
Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.
“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.
Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.
Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.
Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.
The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.
In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.
FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.
At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).
Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).
In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).
In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.
In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.
“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.
Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.
“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.
Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.
Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.
Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.
The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.
In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.
FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.
At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).
Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).
In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).
In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.
In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.
“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.
Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.
“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.
Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.
Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.
Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.
The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA panel urges caution with skin cancer–detecting tools
A and how to address longstanding issues of racial equity in this field of medicine.
The Food and Drug Administration has scheduled two meetings to gather expert feedback about managing an expected expansion in the use of skin lesion apps and devices. Outside of the United States, there are apps promoted as being able to help spot skin lesions that should trigger a medical visit.
The general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee began work on this topic on July 28, with a wide-ranging discussion about potential expanded use of computer-aided, skin lesion analyzer (SLA) devices. On Friday, the panel is considering an FDA proposal to shift the designation for an approved device for aiding dermatologists in skin cancer diagnoses from the most stringent regulatory category, class III, to the less restrictive class II.
The FDA called the meeting amid growing interest in using technology to aid in finding cancers, with some of these products already marketed to consumers outside of the United States. There are presently no legally marketed, FDA-cleared or FDA-approved SLA devices indicated for use by clinicians other than dermatologists or the lay public, the agency said in a briefing memo for the meeting. There are two devices with FDA approval, though, for aiding dermatologists. The FDA approved SciBase’s Nevisense in 2017 and Mela Sciences’ MelaFind, which has fallen out of use, in 2012. Both are class III devices.
But some companies intend to offer products for consumers in the United States. The company SkinVision, for example, has developed an app of the same name, which is intended to detect suspicious-looking skin spots via smartphone photos. SkinVision’s website says the product has been offered to consumers in Australia for remote skin checks since 2015. People in the Netherlands and United Kingdom also can use SkinVision, according to the company’s website. SkinVision says the company is working on providing the app for U.S. customers, “but we are not quite there yet.”
During the meeting, FDA panelists repeatedly emphasized the potential risks of these devices in terms of sensitivity (how often a test correctly generates a positive result) and of specificity (how often a test correctly generates a negative result).
New tools intended to aid in detection of skin cancer might produce too many false positives and thus trigger floods of worried patients seeking care and often facing unnecessary biopsies, the FDA panelists said. But more worrisome would be FDA clearance of tools that delivered too many false negative results, leaving people unaware of their cancers.
The standards would have to be set very high for new products, especially those intended for consumers, said FDA panelist Murad Alam, MD, a dermatologist and vice chair of the department of dermatology at Northwestern University, Chicago. Current technologies for analyzing skin lesions are not yet up to that task. Dr. Alam likened the situation to the hopes for self-driving cars.
“It sounds great in principle. If you read the predictions from 20 years ago, it should already have happened,” Dr. Alam said. “But we’re still struggling with that because there are serious points of failure.”
FDA panelist Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York, also argued for well-designed studies to understand how consumers and clinicians would react to new tools.
“We have to define what prospective information, in the intended use setting, we need to feel comfortable saying that these tools could be in a layperson’s hand or a primary care person’s hand,” Dr. Rotemberg said.
The studies would not need to be large, especially in the case of nonmelanoma skin cancer, which is common, she added.
“There’s too much nuance here for us to be able to say: ‘This is what would happen,’ without testing it,” Dr. Rotemberg said. “I do not think these prospective studies would be very burdensome, but they would help us understand what the burden would be and what the costs would be and what the potential harms would be.”
Because of rules against disclosing corporate information, the FDA cannot tell the public about the kinds of inquiries it already may have fielded from companies interested in selling skin cancer detection tools.
But in response to a question during the FDA meeting, Binita Ashar, MD, a top official in the FDA’s Center for Devices and Radiological Health, said there is interest in having these kinds of products sold in the United States as well.
“I can tell you that this a very timely discussion and questions that we’re posing to you are the questions that we’re encountering or that we have been grappling with,” Dr. Ashar said.
FDA panelists noted that many patients cannot get access easily to dermatology visits.
Companies seeking to develop SLA devices likely will market their tools as attempts to fill a gap that now exists in medical care.
But there will be challenges ahead in explaining to patients how to interpret readings from these tools, the FDA panelists said. Consumers should know these tools are meant to assist in diagnosis, and not to make it.
“I’m not sure the layperson will hear that,” said FDA panelist Paula E. Bourelly, MD, a dermatologist from Olney, Md.
As a result, use of SLA tools could create tension between physicians and patients, with consumers demanding biopsies after seeing readings they don’t understand.
“I do have great concerns about the layperson feeling overly confident and reducing the provider to a technician,” she said.
The FDA panelists were not asked to cast formal votes on any issues discussed during the meeting They instead engaged in broad discussions around questions posed by the FDA in three key areas:
- What standards should be used to confirm lesion diagnosis in clinical testing of the accuracy of SLA devices?
- What would be acceptable true false-positive and false-negative results (sensitivity and specificity) for different diagnoses and users?
- How can the FDA address health equity considerations based on variable incidence of skin lesions?
Developing standards
The FDA asked the panel to consider several scenarios for SLA devices and to discuss how standards might vary depending on the user of the device, whether it would be dermatologists, other clinicians, or consumers.
The agency sought comments in particular about using histological diagnosis (core specimen processing with a consensus diagnosis from an expert dermatopathologist panel). In the briefing document for the meeting, the FDA argued that this approach provides the greatest certainty in the diagnosis.
“Device developers, however, cite concerns, both practical and ethical, in requiring biopsy of all lesions, particularly those that appear benign,” the FDA said. “They have proposed alternate means of defining ground truth, including consensus opinion of experts (of visual or dermoscopic examination of the lesion[s]), opinion of one expert (visual or dermoscopic examination), or other methods.”
In summarizing the discussion on this question, the FDA panel chairman, Hobart W. Harris, MD, MPH, a surgeon from the University of California, San Francisco, noted that there was broad support for histological data in clinical trials of SLA devices, with some allowance for cases where more hybrid approaches would be used.
There were also suggestions offered about designing trials and the need for biopsies of lesions that are clearly benign, as this would help gather data to help in developing algorithms.
Dr. Alam said care should be taken in explaining to study participants that they might have to undergo biopsies that they didn’t need, as part of the larger effort to gather data. This should be detailed in the consent form, he said.
“But I also think this is a relatively minor risk,” Dr. Alam said, comparing these biopsies to the blood samples that patients in many clinical studies routinely give.
“Are all of those blood draws necessary to track the change in whatever parameters that are being tracked? Probably not,” Dr. Alam said. “I think it would be possible to explain to a reasonable patient what this entails.”
Dr. Alam noted that companies might face extra hurdles in enrolling study participants and keeping them in the trials if the FDA seeks this kind of biopsy data. “But I don’t think inconvenience to the study sponsor is a good argument” for not seeking this kind of data, he added.
Leaving a loophole where certain kinds of clearly benign lesions don’t require a biopsy would eventually erode the quality of the research done on these devices. “That bar will be moved to accommodate the convenience of the sponsor, to make the study feasible,” Dr. Alam said. “And pretty soon, you’ll be missing a lot of patients that really should have biopsies.”
Acceptable rates of false positives, false negatives
The FDA panel chair noted that his colleagues had strongly urged review standards that would require that the devices improve on the rates of successful catches of suspicious lesions and lower false positives. But they did not endorse specific targets regarding the sensitivity and specificity rates.
“No one seems to be comfortable with providing or preordaining” these targets, Dr. Harris said.
Panelist Deneen Hesser, MSHSA, RN, urged a deep recognition of the power of a FDA clearance in the view of consumers.
“We need to be cognizant of what the term ‘FDA approved’ means to the lay individual,” said Ms. Hesser, who served as the patient representative on the panel. “A patient who sees that those tools are FDA approved will assume that each of those is the gold standard” in terms of expectations for delivering accurate results.
Like many of the panelists, Dr. Rotemberg urged the FDA to gather data about how patients would react to different messages encoded in consumer-oriented products.
“If the device says: ‘You should see a dermatologist for this’ and no other information, that’s very different from [saying]: ‘That lesion is suspicious for melanoma,’ ” Dr. Rotemberg said.
Despite the likely difficulties in conducting trials, the FDA needs to have the data to answer key questions about patient and physician reactions to readings from new tools, Dr. Rotemberg said.
“We don’t know how many additional biopsies we would cause with a specificity of 80%” for a new SLA tool, Dr. Rotemberg said, giving an example. “We don’t know how confident a dermatologist might be to say: ‘Actually, I’m not suspicious about that lesion and we can just fudge it or not biopsy it.’ We don’t know any of that until we study it in real life.”
The panelists also urged the FDA to seek to ensure that new tools used in analyzing skin lesions improve the quality of diagnosis.
Addressing equity
The FDA also asked the panel to weigh in on whether the agency should clear SLA tools in cases where the existing study data is drawn heavily from people considered to be at higher risk for skin cancer.
“To ensure generalizability across the entire U.S. population, should FDA require SLAs indicated for use beyond cancerous lesions be tested in a representative U.S. population?” the FDA asked.
The three most common skin cancers – melanoma, basal cell carcinoma, and squamous cell carcinoma – are more prevalent in people with Fitzpatrick I and II skin types, who tend to get sunburns, not tans. But people of color are more likely to develop melanoma in areas that are not sun exposed, such as the sole of the foot or under fingernails or toenails.
“Due in part to lower expected risk and screening, these melanomas are often detected late,” the FDA said in the briefing document.
There was broad consensus among panelists that the FDA should encourage companies to enroll people with all skin types and tones.
But they also looked for ways that the FDA could clear devices based on initial studies conducted largely with people considered to be at higher risk, with the agency then requiring follow-up trials to see how these products would work for the general U.S. population.
A version of this article first appeared on Medscape.com.
A and how to address longstanding issues of racial equity in this field of medicine.
The Food and Drug Administration has scheduled two meetings to gather expert feedback about managing an expected expansion in the use of skin lesion apps and devices. Outside of the United States, there are apps promoted as being able to help spot skin lesions that should trigger a medical visit.
The general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee began work on this topic on July 28, with a wide-ranging discussion about potential expanded use of computer-aided, skin lesion analyzer (SLA) devices. On Friday, the panel is considering an FDA proposal to shift the designation for an approved device for aiding dermatologists in skin cancer diagnoses from the most stringent regulatory category, class III, to the less restrictive class II.
The FDA called the meeting amid growing interest in using technology to aid in finding cancers, with some of these products already marketed to consumers outside of the United States. There are presently no legally marketed, FDA-cleared or FDA-approved SLA devices indicated for use by clinicians other than dermatologists or the lay public, the agency said in a briefing memo for the meeting. There are two devices with FDA approval, though, for aiding dermatologists. The FDA approved SciBase’s Nevisense in 2017 and Mela Sciences’ MelaFind, which has fallen out of use, in 2012. Both are class III devices.
But some companies intend to offer products for consumers in the United States. The company SkinVision, for example, has developed an app of the same name, which is intended to detect suspicious-looking skin spots via smartphone photos. SkinVision’s website says the product has been offered to consumers in Australia for remote skin checks since 2015. People in the Netherlands and United Kingdom also can use SkinVision, according to the company’s website. SkinVision says the company is working on providing the app for U.S. customers, “but we are not quite there yet.”
During the meeting, FDA panelists repeatedly emphasized the potential risks of these devices in terms of sensitivity (how often a test correctly generates a positive result) and of specificity (how often a test correctly generates a negative result).
New tools intended to aid in detection of skin cancer might produce too many false positives and thus trigger floods of worried patients seeking care and often facing unnecessary biopsies, the FDA panelists said. But more worrisome would be FDA clearance of tools that delivered too many false negative results, leaving people unaware of their cancers.
The standards would have to be set very high for new products, especially those intended for consumers, said FDA panelist Murad Alam, MD, a dermatologist and vice chair of the department of dermatology at Northwestern University, Chicago. Current technologies for analyzing skin lesions are not yet up to that task. Dr. Alam likened the situation to the hopes for self-driving cars.
“It sounds great in principle. If you read the predictions from 20 years ago, it should already have happened,” Dr. Alam said. “But we’re still struggling with that because there are serious points of failure.”
FDA panelist Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York, also argued for well-designed studies to understand how consumers and clinicians would react to new tools.
“We have to define what prospective information, in the intended use setting, we need to feel comfortable saying that these tools could be in a layperson’s hand or a primary care person’s hand,” Dr. Rotemberg said.
The studies would not need to be large, especially in the case of nonmelanoma skin cancer, which is common, she added.
“There’s too much nuance here for us to be able to say: ‘This is what would happen,’ without testing it,” Dr. Rotemberg said. “I do not think these prospective studies would be very burdensome, but they would help us understand what the burden would be and what the costs would be and what the potential harms would be.”
Because of rules against disclosing corporate information, the FDA cannot tell the public about the kinds of inquiries it already may have fielded from companies interested in selling skin cancer detection tools.
But in response to a question during the FDA meeting, Binita Ashar, MD, a top official in the FDA’s Center for Devices and Radiological Health, said there is interest in having these kinds of products sold in the United States as well.
“I can tell you that this a very timely discussion and questions that we’re posing to you are the questions that we’re encountering or that we have been grappling with,” Dr. Ashar said.
FDA panelists noted that many patients cannot get access easily to dermatology visits.
Companies seeking to develop SLA devices likely will market their tools as attempts to fill a gap that now exists in medical care.
But there will be challenges ahead in explaining to patients how to interpret readings from these tools, the FDA panelists said. Consumers should know these tools are meant to assist in diagnosis, and not to make it.
“I’m not sure the layperson will hear that,” said FDA panelist Paula E. Bourelly, MD, a dermatologist from Olney, Md.
As a result, use of SLA tools could create tension between physicians and patients, with consumers demanding biopsies after seeing readings they don’t understand.
“I do have great concerns about the layperson feeling overly confident and reducing the provider to a technician,” she said.
The FDA panelists were not asked to cast formal votes on any issues discussed during the meeting They instead engaged in broad discussions around questions posed by the FDA in three key areas:
- What standards should be used to confirm lesion diagnosis in clinical testing of the accuracy of SLA devices?
- What would be acceptable true false-positive and false-negative results (sensitivity and specificity) for different diagnoses and users?
- How can the FDA address health equity considerations based on variable incidence of skin lesions?
Developing standards
The FDA asked the panel to consider several scenarios for SLA devices and to discuss how standards might vary depending on the user of the device, whether it would be dermatologists, other clinicians, or consumers.
The agency sought comments in particular about using histological diagnosis (core specimen processing with a consensus diagnosis from an expert dermatopathologist panel). In the briefing document for the meeting, the FDA argued that this approach provides the greatest certainty in the diagnosis.
“Device developers, however, cite concerns, both practical and ethical, in requiring biopsy of all lesions, particularly those that appear benign,” the FDA said. “They have proposed alternate means of defining ground truth, including consensus opinion of experts (of visual or dermoscopic examination of the lesion[s]), opinion of one expert (visual or dermoscopic examination), or other methods.”
In summarizing the discussion on this question, the FDA panel chairman, Hobart W. Harris, MD, MPH, a surgeon from the University of California, San Francisco, noted that there was broad support for histological data in clinical trials of SLA devices, with some allowance for cases where more hybrid approaches would be used.
There were also suggestions offered about designing trials and the need for biopsies of lesions that are clearly benign, as this would help gather data to help in developing algorithms.
Dr. Alam said care should be taken in explaining to study participants that they might have to undergo biopsies that they didn’t need, as part of the larger effort to gather data. This should be detailed in the consent form, he said.
“But I also think this is a relatively minor risk,” Dr. Alam said, comparing these biopsies to the blood samples that patients in many clinical studies routinely give.
“Are all of those blood draws necessary to track the change in whatever parameters that are being tracked? Probably not,” Dr. Alam said. “I think it would be possible to explain to a reasonable patient what this entails.”
Dr. Alam noted that companies might face extra hurdles in enrolling study participants and keeping them in the trials if the FDA seeks this kind of biopsy data. “But I don’t think inconvenience to the study sponsor is a good argument” for not seeking this kind of data, he added.
Leaving a loophole where certain kinds of clearly benign lesions don’t require a biopsy would eventually erode the quality of the research done on these devices. “That bar will be moved to accommodate the convenience of the sponsor, to make the study feasible,” Dr. Alam said. “And pretty soon, you’ll be missing a lot of patients that really should have biopsies.”
Acceptable rates of false positives, false negatives
The FDA panel chair noted that his colleagues had strongly urged review standards that would require that the devices improve on the rates of successful catches of suspicious lesions and lower false positives. But they did not endorse specific targets regarding the sensitivity and specificity rates.
“No one seems to be comfortable with providing or preordaining” these targets, Dr. Harris said.
Panelist Deneen Hesser, MSHSA, RN, urged a deep recognition of the power of a FDA clearance in the view of consumers.
“We need to be cognizant of what the term ‘FDA approved’ means to the lay individual,” said Ms. Hesser, who served as the patient representative on the panel. “A patient who sees that those tools are FDA approved will assume that each of those is the gold standard” in terms of expectations for delivering accurate results.
Like many of the panelists, Dr. Rotemberg urged the FDA to gather data about how patients would react to different messages encoded in consumer-oriented products.
“If the device says: ‘You should see a dermatologist for this’ and no other information, that’s very different from [saying]: ‘That lesion is suspicious for melanoma,’ ” Dr. Rotemberg said.
Despite the likely difficulties in conducting trials, the FDA needs to have the data to answer key questions about patient and physician reactions to readings from new tools, Dr. Rotemberg said.
“We don’t know how many additional biopsies we would cause with a specificity of 80%” for a new SLA tool, Dr. Rotemberg said, giving an example. “We don’t know how confident a dermatologist might be to say: ‘Actually, I’m not suspicious about that lesion and we can just fudge it or not biopsy it.’ We don’t know any of that until we study it in real life.”
The panelists also urged the FDA to seek to ensure that new tools used in analyzing skin lesions improve the quality of diagnosis.
Addressing equity
The FDA also asked the panel to weigh in on whether the agency should clear SLA tools in cases where the existing study data is drawn heavily from people considered to be at higher risk for skin cancer.
“To ensure generalizability across the entire U.S. population, should FDA require SLAs indicated for use beyond cancerous lesions be tested in a representative U.S. population?” the FDA asked.
The three most common skin cancers – melanoma, basal cell carcinoma, and squamous cell carcinoma – are more prevalent in people with Fitzpatrick I and II skin types, who tend to get sunburns, not tans. But people of color are more likely to develop melanoma in areas that are not sun exposed, such as the sole of the foot or under fingernails or toenails.
“Due in part to lower expected risk and screening, these melanomas are often detected late,” the FDA said in the briefing document.
There was broad consensus among panelists that the FDA should encourage companies to enroll people with all skin types and tones.
But they also looked for ways that the FDA could clear devices based on initial studies conducted largely with people considered to be at higher risk, with the agency then requiring follow-up trials to see how these products would work for the general U.S. population.
A version of this article first appeared on Medscape.com.
A and how to address longstanding issues of racial equity in this field of medicine.
The Food and Drug Administration has scheduled two meetings to gather expert feedback about managing an expected expansion in the use of skin lesion apps and devices. Outside of the United States, there are apps promoted as being able to help spot skin lesions that should trigger a medical visit.
The general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee began work on this topic on July 28, with a wide-ranging discussion about potential expanded use of computer-aided, skin lesion analyzer (SLA) devices. On Friday, the panel is considering an FDA proposal to shift the designation for an approved device for aiding dermatologists in skin cancer diagnoses from the most stringent regulatory category, class III, to the less restrictive class II.
The FDA called the meeting amid growing interest in using technology to aid in finding cancers, with some of these products already marketed to consumers outside of the United States. There are presently no legally marketed, FDA-cleared or FDA-approved SLA devices indicated for use by clinicians other than dermatologists or the lay public, the agency said in a briefing memo for the meeting. There are two devices with FDA approval, though, for aiding dermatologists. The FDA approved SciBase’s Nevisense in 2017 and Mela Sciences’ MelaFind, which has fallen out of use, in 2012. Both are class III devices.
But some companies intend to offer products for consumers in the United States. The company SkinVision, for example, has developed an app of the same name, which is intended to detect suspicious-looking skin spots via smartphone photos. SkinVision’s website says the product has been offered to consumers in Australia for remote skin checks since 2015. People in the Netherlands and United Kingdom also can use SkinVision, according to the company’s website. SkinVision says the company is working on providing the app for U.S. customers, “but we are not quite there yet.”
During the meeting, FDA panelists repeatedly emphasized the potential risks of these devices in terms of sensitivity (how often a test correctly generates a positive result) and of specificity (how often a test correctly generates a negative result).
New tools intended to aid in detection of skin cancer might produce too many false positives and thus trigger floods of worried patients seeking care and often facing unnecessary biopsies, the FDA panelists said. But more worrisome would be FDA clearance of tools that delivered too many false negative results, leaving people unaware of their cancers.
The standards would have to be set very high for new products, especially those intended for consumers, said FDA panelist Murad Alam, MD, a dermatologist and vice chair of the department of dermatology at Northwestern University, Chicago. Current technologies for analyzing skin lesions are not yet up to that task. Dr. Alam likened the situation to the hopes for self-driving cars.
“It sounds great in principle. If you read the predictions from 20 years ago, it should already have happened,” Dr. Alam said. “But we’re still struggling with that because there are serious points of failure.”
FDA panelist Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center, New York, also argued for well-designed studies to understand how consumers and clinicians would react to new tools.
“We have to define what prospective information, in the intended use setting, we need to feel comfortable saying that these tools could be in a layperson’s hand or a primary care person’s hand,” Dr. Rotemberg said.
The studies would not need to be large, especially in the case of nonmelanoma skin cancer, which is common, she added.
“There’s too much nuance here for us to be able to say: ‘This is what would happen,’ without testing it,” Dr. Rotemberg said. “I do not think these prospective studies would be very burdensome, but they would help us understand what the burden would be and what the costs would be and what the potential harms would be.”
Because of rules against disclosing corporate information, the FDA cannot tell the public about the kinds of inquiries it already may have fielded from companies interested in selling skin cancer detection tools.
But in response to a question during the FDA meeting, Binita Ashar, MD, a top official in the FDA’s Center for Devices and Radiological Health, said there is interest in having these kinds of products sold in the United States as well.
“I can tell you that this a very timely discussion and questions that we’re posing to you are the questions that we’re encountering or that we have been grappling with,” Dr. Ashar said.
FDA panelists noted that many patients cannot get access easily to dermatology visits.
Companies seeking to develop SLA devices likely will market their tools as attempts to fill a gap that now exists in medical care.
But there will be challenges ahead in explaining to patients how to interpret readings from these tools, the FDA panelists said. Consumers should know these tools are meant to assist in diagnosis, and not to make it.
“I’m not sure the layperson will hear that,” said FDA panelist Paula E. Bourelly, MD, a dermatologist from Olney, Md.
As a result, use of SLA tools could create tension between physicians and patients, with consumers demanding biopsies after seeing readings they don’t understand.
“I do have great concerns about the layperson feeling overly confident and reducing the provider to a technician,” she said.
The FDA panelists were not asked to cast formal votes on any issues discussed during the meeting They instead engaged in broad discussions around questions posed by the FDA in three key areas:
- What standards should be used to confirm lesion diagnosis in clinical testing of the accuracy of SLA devices?
- What would be acceptable true false-positive and false-negative results (sensitivity and specificity) for different diagnoses and users?
- How can the FDA address health equity considerations based on variable incidence of skin lesions?
Developing standards
The FDA asked the panel to consider several scenarios for SLA devices and to discuss how standards might vary depending on the user of the device, whether it would be dermatologists, other clinicians, or consumers.
The agency sought comments in particular about using histological diagnosis (core specimen processing with a consensus diagnosis from an expert dermatopathologist panel). In the briefing document for the meeting, the FDA argued that this approach provides the greatest certainty in the diagnosis.
“Device developers, however, cite concerns, both practical and ethical, in requiring biopsy of all lesions, particularly those that appear benign,” the FDA said. “They have proposed alternate means of defining ground truth, including consensus opinion of experts (of visual or dermoscopic examination of the lesion[s]), opinion of one expert (visual or dermoscopic examination), or other methods.”
In summarizing the discussion on this question, the FDA panel chairman, Hobart W. Harris, MD, MPH, a surgeon from the University of California, San Francisco, noted that there was broad support for histological data in clinical trials of SLA devices, with some allowance for cases where more hybrid approaches would be used.
There were also suggestions offered about designing trials and the need for biopsies of lesions that are clearly benign, as this would help gather data to help in developing algorithms.
Dr. Alam said care should be taken in explaining to study participants that they might have to undergo biopsies that they didn’t need, as part of the larger effort to gather data. This should be detailed in the consent form, he said.
“But I also think this is a relatively minor risk,” Dr. Alam said, comparing these biopsies to the blood samples that patients in many clinical studies routinely give.
“Are all of those blood draws necessary to track the change in whatever parameters that are being tracked? Probably not,” Dr. Alam said. “I think it would be possible to explain to a reasonable patient what this entails.”
Dr. Alam noted that companies might face extra hurdles in enrolling study participants and keeping them in the trials if the FDA seeks this kind of biopsy data. “But I don’t think inconvenience to the study sponsor is a good argument” for not seeking this kind of data, he added.
Leaving a loophole where certain kinds of clearly benign lesions don’t require a biopsy would eventually erode the quality of the research done on these devices. “That bar will be moved to accommodate the convenience of the sponsor, to make the study feasible,” Dr. Alam said. “And pretty soon, you’ll be missing a lot of patients that really should have biopsies.”
Acceptable rates of false positives, false negatives
The FDA panel chair noted that his colleagues had strongly urged review standards that would require that the devices improve on the rates of successful catches of suspicious lesions and lower false positives. But they did not endorse specific targets regarding the sensitivity and specificity rates.
“No one seems to be comfortable with providing or preordaining” these targets, Dr. Harris said.
Panelist Deneen Hesser, MSHSA, RN, urged a deep recognition of the power of a FDA clearance in the view of consumers.
“We need to be cognizant of what the term ‘FDA approved’ means to the lay individual,” said Ms. Hesser, who served as the patient representative on the panel. “A patient who sees that those tools are FDA approved will assume that each of those is the gold standard” in terms of expectations for delivering accurate results.
Like many of the panelists, Dr. Rotemberg urged the FDA to gather data about how patients would react to different messages encoded in consumer-oriented products.
“If the device says: ‘You should see a dermatologist for this’ and no other information, that’s very different from [saying]: ‘That lesion is suspicious for melanoma,’ ” Dr. Rotemberg said.
Despite the likely difficulties in conducting trials, the FDA needs to have the data to answer key questions about patient and physician reactions to readings from new tools, Dr. Rotemberg said.
“We don’t know how many additional biopsies we would cause with a specificity of 80%” for a new SLA tool, Dr. Rotemberg said, giving an example. “We don’t know how confident a dermatologist might be to say: ‘Actually, I’m not suspicious about that lesion and we can just fudge it or not biopsy it.’ We don’t know any of that until we study it in real life.”
The panelists also urged the FDA to seek to ensure that new tools used in analyzing skin lesions improve the quality of diagnosis.
Addressing equity
The FDA also asked the panel to weigh in on whether the agency should clear SLA tools in cases where the existing study data is drawn heavily from people considered to be at higher risk for skin cancer.
“To ensure generalizability across the entire U.S. population, should FDA require SLAs indicated for use beyond cancerous lesions be tested in a representative U.S. population?” the FDA asked.
The three most common skin cancers – melanoma, basal cell carcinoma, and squamous cell carcinoma – are more prevalent in people with Fitzpatrick I and II skin types, who tend to get sunburns, not tans. But people of color are more likely to develop melanoma in areas that are not sun exposed, such as the sole of the foot or under fingernails or toenails.
“Due in part to lower expected risk and screening, these melanomas are often detected late,” the FDA said in the briefing document.
There was broad consensus among panelists that the FDA should encourage companies to enroll people with all skin types and tones.
But they also looked for ways that the FDA could clear devices based on initial studies conducted largely with people considered to be at higher risk, with the agency then requiring follow-up trials to see how these products would work for the general U.S. population.
A version of this article first appeared on Medscape.com.
Avoiding harm in the diagnosis and treatment of food allergies
INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that
“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.
During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.
While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”
Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.
Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”
Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.
“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.
The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”
Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.
“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”
IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.
“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).
With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.
“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”
He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”
Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?
“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.
According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.
“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”
Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.
INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that
“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.
During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.
While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”
Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.
Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”
Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.
“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.
The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”
Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.
“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”
IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.
“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).
With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.
“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”
He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”
Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?
“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.
According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.
“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”
Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.
INDIANAPOLIS – If there’s one truth that David R. Stukus, MD, has come to realize from his 2 years as director of a food allergy treatment center, it’s that
“When they’re given a diagnosis of food allergy, many families do not receive proper education to help them understand the risk as well as self-management and prognosis,” he said at the annual meeting of the Society for Pediatric Dermatology. “They are left to fend for themselves, which leads to increased anxiety. If they don’t understand what it means to manage their child’s food allergy, they’re going to think that they’re a ticking time bomb,” said Dr. Stukus, director of the Food Allergy Treatment Center and professor of pediatrics in the division of allergy and immunology at Nationwide Children’s Hospital in Columbus, Ohio.
During his presentation, he toured clinicians through best practices to diagnose and treat food allergies and shared cautionary tales of unsupported claims, unnecessary testing, and potential harm to misdiagnosed patients.
While food allergies can be serious and life-threatening, they are also manageable, he continued. It doesn’t mean that children with food allergies can’t go to school, attend baseball games, or participate in activities that any other child would. “Telling someone to adopt a restricted diet is not a benign recommendation,” he said. “That can cause real harm.”
Dr. Stukus defined food allergy as an immunologic response to an allergen that results in reproducible symptoms with every exposure. “Most commonly we’re going to see IgE-mediated food allergies, which often occur within minutes of eating certain foods,” he said.
Food intolerance, on the other hand, is a nonimmunologic response to a food that causes gastrointestinal symptoms with exposure. “This can come and go over time,” he said. “The most common example is lactose intolerance.”
Then there’s food sensitivity, which Dr. Stukus said is not a medical term but a marketing term often applied to a variety of symptoms without evidence to support its use.
“On the Internet you will find many companies marketing food sensitivity tests,” he said. “Gluten-free foods are now a billion-dollar industry. There are no validated tests to diagnose food sensitivity. All the blood tests measure IgG, which is memory antibody. If you eat a food, it is a normal response to produce IgG to it, but these companies will test all these things and when it comes back elevated, they say ‘Aha! This is your food sensitivity and this is why you’re not sleeping well at night.’ ” To illustrate the harm that can come from food allergy tests he discussed a 6-year-old girl who presented to his clinic several years ago with typical symptoms of allergic rhinitis. The parent reported a history of sneezing around dogs, itchy, watery eyes in the spring, recurrent cough, and frequent upper respiratory infections.
The referring physician had ordered an allergy panel, which flagged a long list of foods that the girl was supposedly allergic to, including banana, egg white, cod, and peanut. “This family was told to take all of these foods out of her diet,” Dr. Stukus said. “Interestingly, she had been seen by this physician for evaluation of environmental allergies, but the only ones included in the test were cat, cockroach, dog, and dust mite. They didn’t even include the spring pollen allergies. You want to avoid tests like this.”
Food sensitization is not the same as food allergy, he continued, noting that about 30% of all children will have detectable IgE toward peanuts, milk, egg, and shrimp, but that only about 5% are truly allergic to those foods.
“If we go by IgE testing alone, we’re going to overdiagnose the vast majority of people with food allergies that they don’t actually have,” he said. “Food allergy is diagnosed by the history and then confirmed by testing. With IgE-mediated food allergies we know that milk, egg, wheat, soy, finned fish, shellfish, and peanuts account for more than 90% of all food allergy reactions. Can any food potentially cause a food allergy? Yes, potentially, but we know that most fruits and vegetables and grains are very unlikely to cause an allergy.”
IgE-mediated food allergies are objective, immediate onset, and reproducible with every exposure to the offending food, no matter what form. Typical symptoms include hives, swelling, vomiting, runny nose/congestion, wheezing, hypotension, and anaphylaxis.
“We can also accurately identify infants that are more at risk to develop food allergies,” Dr. Stukus said. Infants with refractory atopic dermatitis often progress from eczema to food allergies to allergic rhinitis and asthma, the so-called “allergic march.” “Family history does have a role as well, but it’s not as significant,” he said. As for diagnostic tools, skin prick testing detects the presence of specific IgE bound to cutaneous mast cells and has a high negative predictive value and a low positive predictive value (around 50%).
With serum-specific IgE testing, levels of IgE for food and/or inhalant allergen can be obtained conveniently through routine venipuncture. Results are reported in ranges from 0.1 kU/L to 100 kU/L, and some are reported as arbitrary classes in levels of severity from 1 to 5.
“I highly discourage anybody from paying attention to arbitrary classes [on these reports],” Dr. Stukus said. “Those are meaningless. The absolute value is all that matters.”
He added that both skin and blood testing have high rates of false positive results. “We really need to use the history to help guide what tests we do; they were never designed to be used as screening tests, yet they’re used as screening tests on a regular basis,” he said. “There is also no indication to do shotgun testing. The reason why is because we see lots of cross reactivity on testing. If we have someone with peanut allergy and we start doing specific IgE testing for all legumes, more often than not we’re going to find detectable IgE, but it’s much less likely that they actually have clinical reactivity to foods like soy and beans.”
Dr. Stukus advises clinicians to consider certain questions before they order an allergen panel, the first being: Do I have the knowledge and experience to properly interpret the results?
“If you don’t know how to interpret the test, you probably shouldn’t order it in the first place,” he said. “If you do have the knowledge to interpret the results, will the results help to determine the diagnosis or change management? If not, why are you testing just to test? There is zero clinical indication to order a food allergy panel.” Dr. Stukus recommended a review of unproven tests for adverse reactions to foods published in 2018 in The Journal of Allergy and Clinical Immunology.
According to Dr. Stukus, potential harms from unproven food allergy tests include cost, unnecessary dietary avoidance, and a delay in diagnosis for the underlying condition. During the COVID-19 pandemic, he observed an increase in the number of patients with orthorexia, which he described as an eating disorder characterized by having an unsafe obsession with healthy food that becomes deeply rooted in the individual’s way of thinking to the point that it interferes with daily life.
“If you take someone who has anxiety at baseline, and then you give them a list of foods that they allegedly can’t eat, that’s going to cause worse anxiety,” he added. “We’re seeing that from the results of these tests.”
Dr. Stukus disclosed that he is a consultant for Before Brands, Kaleo, and Novartis. He is also associate editor of the Annals of Allergy, Asthma and Immunology.
AT SPD 2022
To gauge monkeypox spread, researchers eye cases in women
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.
So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.
Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).
“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”
A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.
Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.
“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.
Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.
A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.
Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.
The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed.
One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.
Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
Transmission dynamics
Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.
Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.
Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
More testing, higher positivity rates in men
Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.
As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.
In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.
Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
Monkeypox and pregnancy
Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.
“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.
With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.
“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.
“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.
During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.
Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.
“Clinicians should bear this in mind when examining any person,” she said.
A version of this article first appeared on Medscape.com.
Toe growth
Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.
Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.
In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.
The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679
2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x
Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.
Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.
In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.
The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.
Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.
In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.
The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.
Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).
1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679
2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x
1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679
2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x
What are your treatment options when isotretinoin fails?
INDIANAPOLIS – – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.
“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.
Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.
If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.
Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.
In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”
The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.
“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”
Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.
Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.
“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”
Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”
Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.
INDIANAPOLIS – – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.
“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.
Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.
If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.
Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.
In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”
The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.
“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”
Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.
Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.
“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”
Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”
Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.
INDIANAPOLIS – – which is known to increase the drug’s bioavailability, advises James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia.
“We see lots of teenagers who are on a restrictive diet,” which is “certainly one reason they could be failing isotretinoin,” Dr. Treat said at the annual meeting of the Society for Pediatric Dermatology.
Often, patients say that they have been referred to him because they had no response to 20 mg or 30 mg per day of isotretinoin. But after a dose escalation to 60 mg per day, their acne worsened.
If the patient’s acne is worsening with a cystic flare, “tripling the dose of isotretinoin is not something that you should do,” Dr. Treat said. “You should lower the dose and consider adding steroids.” For evidence-based recommendations on managing acne fulminans, he recommended an article published in the Journal of the American Academy of Dermatology in 2017.
Skin picking is another common reason for failure of isotretinoin, as well as with other acne therapies. These patients may have associated anxiety, which “might be a contraindication or at least something to consider before you put them on isotretinoin,” he noted.
In his experience, off-label use of N-acetylcysteine, an antioxidant and cysteine prodrug, has been “extremely effective” for patients with excoriation disorder. In a randomized trial of adults 18-60 years of age, 47% patients who took 1,200-3,000 mg per day doses of N-acetylcysteine for 12 weeks reported that their skin picking was much or very much improved, compared to 19% of those who took placebo (P = .03). The authors wrote that N-acetylcysteine “increases extracellular levels of glutamate in the nucleus accumbens,” and that these results support the hypothesis that “pharmacologic manipulation of the glutamate system may target core symptoms of compulsive behaviors.”
The tumor necrosis factor (TNF)-alpha blocker adalimumab is a reasonable option for patients with severe cystic inflammatory acne who fail isotretinoin, Dr. Treat said. In one published case, clinicians administered adalimumab 40 mg every other week for a 16-year-old male patient who received isotretinoin for moderate acne vulgaris, which caused sudden development of acne fulminans and incapacitating acute sacroiliitis with bilateral hip arthritis. Inflammatory lesions started to clear in 1 month and comedones improved by 3 months of treatment. Adalimumab was discontinued after 1 year and the patient remained clear.
“There are now multiple reports as well as some case series showing TNF-alpha agents causing clearance of acne,” said Dr. Treat, who directs the hospital’s pediatric dermatology fellowship program. A literature review of adalimumab, etanercept, and infliximab for treatment-resistant acne found that all agents had similar efficacy after 3-6 months of therapy. “We see this in our GI population, where TNF-alpha agents are helping their acne also,” he said. “We just have to augment it with some topical medications.”
Certain medications can drive the development of acne, including phenytoin, phenobarbital, lithium, MEK inhibitors, EGFR inhibitors, systemic steroids, and unopposed progesterone contraceptives. Some genetic conditions also predispose patients to acne, including mutations in the NCSTN gene and trisomy 13.
Dr. Treat discussed one of his patients with severe acne who had trisomy 13. The patient failed 12 months of doxycycline and amoxicillin in combination with a topical retinoid. He also failed low- and high-dose isotretinoin in combination with prednisone, as well as oral dapsone at a dose of 1 mg/kg per day for 3 months. He was started on adalimumab, but that was stopped after he flared. The patient is now maintained on ustekinumab monthly at a dose of 45 mg.
“I’ve only had a few patients where isotretinoin truly has failed,” Dr. Treat said. He described one patient with severe acne who had a hidradenitis-like appearance in his axilla and groin. “I treated with isotretinoin very gingerly in the beginning, [but] he flared significantly. I had given him concomitant steroids from the very beginning and transitioned to multiple different therapies – all of which failed.”
Next, Dr. Treat tried a course of systemic dapsone, and the patient responded nicely. “As an anti-inflammatory agent, dapsone is very reasonable” to consider, he said. “It’s something to add to your armamentarium.”
Dr. Treat disclosed that he is a consultant for Palvella and Regeneron. He has ownership interests in Matinas Biopharma Holdings, Axsome, Sorrento, and Amarin.
AT SPD 2022
Questionnaire for patients with psoriasis might identify risk of axial involvement
Preliminary findings are encouraging
NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.
There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.
While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.
There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.
In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.
“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.
The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.
In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:
- Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
- Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
- The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.
Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
AxSpA screening tool ‘makes sense’ for potential use in PsA
The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.
Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.
Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.
“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.
The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.
If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.
When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.
“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.
“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.
In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.
“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.
Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.
Preliminary findings are encouraging
Preliminary findings are encouraging
NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.
There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.
While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.
There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.
In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.
“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.
The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.
In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:
- Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
- Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
- The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.
Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
AxSpA screening tool ‘makes sense’ for potential use in PsA
The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.
Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.
Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.
“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.
The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.
If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.
When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.
“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.
“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.
In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.
“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.
Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.
NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.
There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.
While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.
There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.
In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.
“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.
The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.
In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:
- Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
- Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
- The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.
Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
AxSpA screening tool ‘makes sense’ for potential use in PsA
The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.
Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.
Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.
“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.
The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.
If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.
When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.
“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.
“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.
In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.
“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.
Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.
AT GRAPPA 2022
Topical gene therapy for dystrophic epidermolysis bullosa shows promise
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
AT SPD 2022
Clinical characteristics of recurrent RIME elucidated in chart review
INDIANAPOLIS – , in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.
Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.
Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.
In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”
A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.
The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.
Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.
The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
Isolated vs. recurrent RIME
However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.
The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.
Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.
“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”
In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.
“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”
She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.
Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.
“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”
The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – , in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.
Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.
Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.
In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”
A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.
The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.
Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.
The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
Isolated vs. recurrent RIME
However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.
The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.
Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.
“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”
In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.
“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”
She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.
Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.
“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”
The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
INDIANAPOLIS – , in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.
Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.
Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.
In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”
A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.
The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.
Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.
The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
Isolated vs. recurrent RIME
However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.
The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.
Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.
“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”
In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.
“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”
She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.
Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.
“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”
The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.
AT SPD 2022
A toddler presents with patchy hair loss
Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).
Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.1 AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.8 Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.9,10
What’s the differential diagnosis?
The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.
Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.
Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.
Lichen planopilaris (LPP) is a scarring, irreversible alopecia caused by T-lymphocytes attacking follicular hair stem cells. It is characterized by hair loss, pruritus, burning pain, scalp scaling, and multifocal scarring. Exam shows patches of alopecia with loss of follicular ostia centrally and perifollicular scale and erythema at the borders. Diagnosis is aided by biopsy of the affected scalp. Treatment of LPP requires the use of potent and superpotent topical corticosteroids and intralesional corticosteroids to decrease scalp inflammation and prevent further progression. The presence of follicular ostia and absence of perifollicular scale in this patient makes LPP highly unlikely.
Tinea capitis is a fungal infection of the scalp caused by dermatophytes including Trychophyton tonsurans and Microsporum canis. It presents with patches of alopecia with overlying scale and broken hairs and can have associated cervical and occipital lymphadenopathy. Diagnosis can involve skin scraping and KOH prep to visualize branching hyphae as well as fungal culture to identify the causative organism. Because dermatophytes in tinea capitis invade hair follicles, topical antifungals are ineffective because of their lack of penetration. Therefore, systemic antifungals including oral terbinafine and griseofulvin are considered first-line agents for treatment.
What’s the management plan?
The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.11 Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.6 For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.12 Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).12 Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.12,13
Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.
References
1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.
2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.
3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.
4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.
5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.
6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.
7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.
8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.
9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.
10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.
11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.
12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.
13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.
Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).
Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.1 AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.8 Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.9,10
What’s the differential diagnosis?
The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.
Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.
Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.
Lichen planopilaris (LPP) is a scarring, irreversible alopecia caused by T-lymphocytes attacking follicular hair stem cells. It is characterized by hair loss, pruritus, burning pain, scalp scaling, and multifocal scarring. Exam shows patches of alopecia with loss of follicular ostia centrally and perifollicular scale and erythema at the borders. Diagnosis is aided by biopsy of the affected scalp. Treatment of LPP requires the use of potent and superpotent topical corticosteroids and intralesional corticosteroids to decrease scalp inflammation and prevent further progression. The presence of follicular ostia and absence of perifollicular scale in this patient makes LPP highly unlikely.
Tinea capitis is a fungal infection of the scalp caused by dermatophytes including Trychophyton tonsurans and Microsporum canis. It presents with patches of alopecia with overlying scale and broken hairs and can have associated cervical and occipital lymphadenopathy. Diagnosis can involve skin scraping and KOH prep to visualize branching hyphae as well as fungal culture to identify the causative organism. Because dermatophytes in tinea capitis invade hair follicles, topical antifungals are ineffective because of their lack of penetration. Therefore, systemic antifungals including oral terbinafine and griseofulvin are considered first-line agents for treatment.
What’s the management plan?
The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.11 Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.6 For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.12 Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).12 Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.12,13
Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.
References
1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.
2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.
3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.
4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.
5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.
6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.
7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.
8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.
9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.
10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.
11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.
12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.
13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.
Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).
Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.1 AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.8 Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.9,10
What’s the differential diagnosis?
The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.
Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.
Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.
Lichen planopilaris (LPP) is a scarring, irreversible alopecia caused by T-lymphocytes attacking follicular hair stem cells. It is characterized by hair loss, pruritus, burning pain, scalp scaling, and multifocal scarring. Exam shows patches of alopecia with loss of follicular ostia centrally and perifollicular scale and erythema at the borders. Diagnosis is aided by biopsy of the affected scalp. Treatment of LPP requires the use of potent and superpotent topical corticosteroids and intralesional corticosteroids to decrease scalp inflammation and prevent further progression. The presence of follicular ostia and absence of perifollicular scale in this patient makes LPP highly unlikely.
Tinea capitis is a fungal infection of the scalp caused by dermatophytes including Trychophyton tonsurans and Microsporum canis. It presents with patches of alopecia with overlying scale and broken hairs and can have associated cervical and occipital lymphadenopathy. Diagnosis can involve skin scraping and KOH prep to visualize branching hyphae as well as fungal culture to identify the causative organism. Because dermatophytes in tinea capitis invade hair follicles, topical antifungals are ineffective because of their lack of penetration. Therefore, systemic antifungals including oral terbinafine and griseofulvin are considered first-line agents for treatment.
What’s the management plan?
The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.11 Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.6 For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.12 Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).12 Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.12,13
Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.
References
1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.
2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.
3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.
4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.
5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.
6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.
7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.
8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.
9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.
10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.
11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.
12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.
13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.
Examination findings of the scalp demonstrate a well-circumscribed alopecic patch on the vertex scalp without erythema or scale. Closer inspection of the patch with magnification or 'dermoscopy' reveals hair follicle ostia and hairs that are broader distally and narrower at their base. Nails and rest of the skin exam are unremarkable.