Dermatology

Well-demarcated, map-like tongue markings are consistent with migratory glossitis, also called geographic tongue, and can be recognized by its distinct clinical appearance. If performed, a biopsy would show psoriasiform mucositis.

Migratory glossitis is an uncommon condition found mostly in adults and occasionally in children. The prevalence may be as high as 2.5% globally and it may occur in conjunction with psoriasis, sharing some histologic features.¹ (On close inspection, this patient was noted to have plaques on his elbows that were consistent with psoriasis.) While an immunogenic cause is suspected, the exact etiology is unknown.

Patients may develop these clinical findings quickly and just as quickly they may resolve. Discomfort and taste disturbances rarely occur. Hot, spicy, or acidic foods may be a contributing trigger. Tobacco-use appears to be protective. The presence of ulceration should prompt evaluation for a different diagnosis, such as erosive lichen planus, leukoplakia, candidiasis, or Behçet syndrome.

With minimal symptoms, treatment is rarely needed. Patients with any discomfort can be treated with topical lidocaine 2% swish and spit mouthwash, topical tacrolimus, or topical steroids.

The patient in this case was reassured that the diagnosis was not concerning and he was observed without active treatment. His psoriasis was treated with topical clobetasol ointment 0.05%. He has continued to have intermittent flares that he has yet to associate with any specific dietary causes.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Well-demarcated, map-like tongue markings are consistent with migratory glossitis, also called geographic tongue, and can be recognized by its distinct clinical appearance. If performed, a biopsy would show psoriasiform mucositis.

Migratory glossitis is an uncommon condition found mostly in adults and occasionally in children. The prevalence may be as high as 2.5% globally and it may occur in conjunction with psoriasis, sharing some histologic features.¹ (On close inspection, this patient was noted to have plaques on his elbows that were consistent with psoriasis.) While an immunogenic cause is suspected, the exact etiology is unknown.

Patients may develop these clinical findings quickly and just as quickly they may resolve. Discomfort and taste disturbances rarely occur. Hot, spicy, or acidic foods may be a contributing trigger. Tobacco-use appears to be protective. The presence of ulceration should prompt evaluation for a different diagnosis, such as erosive lichen planus, leukoplakia, candidiasis, or Behçet syndrome.

With minimal symptoms, treatment is rarely needed. Patients with any discomfort can be treated with topical lidocaine 2% swish and spit mouthwash, topical tacrolimus, or topical steroids.

The patient in this case was reassured that the diagnosis was not concerning and he was observed without active treatment. His psoriasis was treated with topical clobetasol ointment 0.05%. He has continued to have intermittent flares that he has yet to associate with any specific dietary causes.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Well-demarcated, map-like tongue markings are consistent with migratory glossitis, also called geographic tongue, and can be recognized by its distinct clinical appearance. If performed, a biopsy would show psoriasiform mucositis.

Migratory glossitis is an uncommon condition found mostly in adults and occasionally in children. The prevalence may be as high as 2.5% globally and it may occur in conjunction with psoriasis, sharing some histologic features.¹ (On close inspection, this patient was noted to have plaques on his elbows that were consistent with psoriasis.) While an immunogenic cause is suspected, the exact etiology is unknown.

Patients may develop these clinical findings quickly and just as quickly they may resolve. Discomfort and taste disturbances rarely occur. Hot, spicy, or acidic foods may be a contributing trigger. Tobacco-use appears to be protective. The presence of ulceration should prompt evaluation for a different diagnosis, such as erosive lichen planus, leukoplakia, candidiasis, or Behçet syndrome.

With minimal symptoms, treatment is rarely needed. Patients with any discomfort can be treated with topical lidocaine 2% swish and spit mouthwash, topical tacrolimus, or topical steroids.

The patient in this case was reassured that the diagnosis was not concerning and he was observed without active treatment. His psoriasis was treated with topical clobetasol ointment 0.05%. He has continued to have intermittent flares that he has yet to associate with any specific dietary causes.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

Transverse ridges that grow out with the nails are called Beau lines, also known as Beau’s ridges. This contrasts with Mees lines which are transverse white bands that grow out with the toenails, are nonpalpable, and are attributed to arsenic poisoning.

Beau lines are caused by a disruption in nail growth that can result from trauma, hypotension, or systemic or severe illness; they have also been reported in cases of COVID-19.¹ Beau lines can occur on a single nail if the trauma or injury is isolated to 1 digit. If there was a systemic illness or stress, the lines can affect all 20 nails. The time of the inciting event can be approximated by how far the lines are from the cuticle. While there is some variability, it usually takes 12 to 18 months to grow an entirely new toenail. If the Beau lines have grown halfway out, then the stressor likely occurred 6 to 9 months earlier.

In this image, some asymmetry is visible between the right and left great toenails and there are some subtle distal changes, raising the possibility that there was more than 1 injury to this patient’s system (or prolonged difficulty). The patient said that to his knowledge, he had not been infected with COVID-19. However, hair and nail changes may be the only finding in some individuals who have been infected with COVID-19.¹

This patient was counseled regarding the nature of this disorder and that without knowing what illness or injury caused the change, it was a benign finding. He was advised that it did not appear to be onychomycosis and did not require any medications or antifungal therapy. The patient was told to follow up if any changes developed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Transverse ridges that grow out with the nails are called Beau lines, also known as Beau’s ridges. This contrasts with Mees lines which are transverse white bands that grow out with the toenails, are nonpalpable, and are attributed to arsenic poisoning.

Beau lines are caused by a disruption in nail growth that can result from trauma, hypotension, or systemic or severe illness; they have also been reported in cases of COVID-19.¹ Beau lines can occur on a single nail if the trauma or injury is isolated to 1 digit. If there was a systemic illness or stress, the lines can affect all 20 nails. The time of the inciting event can be approximated by how far the lines are from the cuticle. While there is some variability, it usually takes 12 to 18 months to grow an entirely new toenail. If the Beau lines have grown halfway out, then the stressor likely occurred 6 to 9 months earlier.

In this image, some asymmetry is visible between the right and left great toenails and there are some subtle distal changes, raising the possibility that there was more than 1 injury to this patient’s system (or prolonged difficulty). The patient said that to his knowledge, he had not been infected with COVID-19. However, hair and nail changes may be the only finding in some individuals who have been infected with COVID-19.¹

This patient was counseled regarding the nature of this disorder and that without knowing what illness or injury caused the change, it was a benign finding. He was advised that it did not appear to be onychomycosis and did not require any medications or antifungal therapy. The patient was told to follow up if any changes developed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Transverse ridges that grow out with the nails are called Beau lines, also known as Beau’s ridges. This contrasts with Mees lines which are transverse white bands that grow out with the toenails, are nonpalpable, and are attributed to arsenic poisoning.

Beau lines are caused by a disruption in nail growth that can result from trauma, hypotension, or systemic or severe illness; they have also been reported in cases of COVID-19.¹ Beau lines can occur on a single nail if the trauma or injury is isolated to 1 digit. If there was a systemic illness or stress, the lines can affect all 20 nails. The time of the inciting event can be approximated by how far the lines are from the cuticle. While there is some variability, it usually takes 12 to 18 months to grow an entirely new toenail. If the Beau lines have grown halfway out, then the stressor likely occurred 6 to 9 months earlier.

In this image, some asymmetry is visible between the right and left great toenails and there are some subtle distal changes, raising the possibility that there was more than 1 injury to this patient’s system (or prolonged difficulty). The patient said that to his knowledge, he had not been infected with COVID-19. However, hair and nail changes may be the only finding in some individuals who have been infected with COVID-19.¹

This patient was counseled regarding the nature of this disorder and that without knowing what illness or injury caused the change, it was a benign finding. He was advised that it did not appear to be onychomycosis and did not require any medications or antifungal therapy. The patient was told to follow up if any changes developed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

A version of this article first appeared on Medscape.com.

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

A version of this article first appeared on Medscape.com.

Oral tofacitinib (Xeljanz), a Janus kinase inhibitor, helped regrow hair in three-quarters of pediatric patients with alopecia areata (AA) in a small study conducted at the University of Colorado and published in Pediatric Dermatology.

The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.

“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.

“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.

The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.

Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
 

Study details

Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.

The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.

Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.

The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.

Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.

“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
 

Other research

In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.

Mechanisms, concerns

The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.

A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.

Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.

At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.

Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.

Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.

A version of this article first appeared on Medscape.com.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.

Common skin reactions to treatment with topical 5-FU for actinic keratosis include erythema, ulceration, and burning. In this case, however, the skin disruption opened the door to secondary impetigo.

Secondary skin infections are a known risk of treatment with topical 5-FU. The agent inhibits thymidylate synthetase, an enzyme involved in the synthesis and repair of DNA. The inhibition of this enzyme can lead to skin disruption with erosion, desquamation, and the risk of superimposed skin infections, as was seen with this patient.¹

Impetigo is a common skin infection affecting the superficial layers of the epidermis and is most commonly caused by gram-positive bacteria, such as Staphylococcus aureus or Streptococcus pyogenes.² Secondary impetigo, also known as impetiginization, is an infection of previously disrupted skin due to eczema, trauma, insect bites, and other conditions. This contrasts with primary impetigo, which results from a direct bacterial invasion of intact healthy skin. While impetigo predominantly affects children between the ages of 2 and 5 years, people of any age can be affected.² Impetigo characteristically manifests with painful erosions, classically covered by honey-colored crusts. Thin-walled vesicles often appear and subsequently rupture.

Treatment options for impetigo include both topical and systemic antibiotics. Topical therapy is preferred for patients with limited skin involvement, while systemic therapy is indicated for patients with numerous lesions. Mupirocin and retapamulin are first-line topical treatments. Systemic antibiotic therapy should provide coverage for both S. aureus and streptococcal infections; cephalexin and dicloxacillin are preferred. Doxycycline, trimethoprim-sulfamethoxazole, or clindamycin can be used if methicillin-resistant Staphylococcus aureus is suspected.³

This patient was advised to try warm soaks (to reduce the crusting) and to follow that with the application of white petrolatum bid. The patient was also prescribed doxycycline 100 mg orally bid for 10 days. At the 1-month follow-up, there was some residual erythema, but the impetigo and crusting had resolved. The actinic keratoses had resolved, as well.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Tess Pei Lemon, BA, University of New Mexico School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Common skin reactions to treatment with topical 5-FU for actinic keratosis include erythema, ulceration, and burning. In this case, however, the skin disruption opened the door to secondary impetigo.

Secondary skin infections are a known risk of treatment with topical 5-FU. The agent inhibits thymidylate synthetase, an enzyme involved in the synthesis and repair of DNA. The inhibition of this enzyme can lead to skin disruption with erosion, desquamation, and the risk of superimposed skin infections, as was seen with this patient.¹

Impetigo is a common skin infection affecting the superficial layers of the epidermis and is most commonly caused by gram-positive bacteria, such as Staphylococcus aureus or Streptococcus pyogenes.² Secondary impetigo, also known as impetiginization, is an infection of previously disrupted skin due to eczema, trauma, insect bites, and other conditions. This contrasts with primary impetigo, which results from a direct bacterial invasion of intact healthy skin. While impetigo predominantly affects children between the ages of 2 and 5 years, people of any age can be affected.² Impetigo characteristically manifests with painful erosions, classically covered by honey-colored crusts. Thin-walled vesicles often appear and subsequently rupture.

Treatment options for impetigo include both topical and systemic antibiotics. Topical therapy is preferred for patients with limited skin involvement, while systemic therapy is indicated for patients with numerous lesions. Mupirocin and retapamulin are first-line topical treatments. Systemic antibiotic therapy should provide coverage for both S. aureus and streptococcal infections; cephalexin and dicloxacillin are preferred. Doxycycline, trimethoprim-sulfamethoxazole, or clindamycin can be used if methicillin-resistant Staphylococcus aureus is suspected.³

This patient was advised to try warm soaks (to reduce the crusting) and to follow that with the application of white petrolatum bid. The patient was also prescribed doxycycline 100 mg orally bid for 10 days. At the 1-month follow-up, there was some residual erythema, but the impetigo and crusting had resolved. The actinic keratoses had resolved, as well.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Tess Pei Lemon, BA, University of New Mexico School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Common skin reactions to treatment with topical 5-FU for actinic keratosis include erythema, ulceration, and burning. In this case, however, the skin disruption opened the door to secondary impetigo.

Secondary skin infections are a known risk of treatment with topical 5-FU. The agent inhibits thymidylate synthetase, an enzyme involved in the synthesis and repair of DNA. The inhibition of this enzyme can lead to skin disruption with erosion, desquamation, and the risk of superimposed skin infections, as was seen with this patient.¹

Impetigo is a common skin infection affecting the superficial layers of the epidermis and is most commonly caused by gram-positive bacteria, such as Staphylococcus aureus or Streptococcus pyogenes.² Secondary impetigo, also known as impetiginization, is an infection of previously disrupted skin due to eczema, trauma, insect bites, and other conditions. This contrasts with primary impetigo, which results from a direct bacterial invasion of intact healthy skin. While impetigo predominantly affects children between the ages of 2 and 5 years, people of any age can be affected.² Impetigo characteristically manifests with painful erosions, classically covered by honey-colored crusts. Thin-walled vesicles often appear and subsequently rupture.

Treatment options for impetigo include both topical and systemic antibiotics. Topical therapy is preferred for patients with limited skin involvement, while systemic therapy is indicated for patients with numerous lesions. Mupirocin and retapamulin are first-line topical treatments. Systemic antibiotic therapy should provide coverage for both S. aureus and streptococcal infections; cephalexin and dicloxacillin are preferred. Doxycycline, trimethoprim-sulfamethoxazole, or clindamycin can be used if methicillin-resistant Staphylococcus aureus is suspected.³

This patient was advised to try warm soaks (to reduce the crusting) and to follow that with the application of white petrolatum bid. The patient was also prescribed doxycycline 100 mg orally bid for 10 days. At the 1-month follow-up, there was some residual erythema, but the impetigo and crusting had resolved. The actinic keratoses had resolved, as well.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Tess Pei Lemon, BA, University of New Mexico School of Medicine and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Erythema multiforme (EM) is a hypersensitivity reaction commonly caused by herpes simplex virus (HSV) infection. Less frequently observable infectious agents associated with EM are Mycoplasma pneumoniae, Histoplasma capsulatum, and parapoxvirus (orf). Rarely, EM is triggered by drug eruption or systemic disease. Individuals of all age groups and races can be affected by EM. However, it is predominantly observed in young adult patients (20-40 years of age), and there is a male predominance.

Patients typically present with the abrupt onset of symmetrical red papules that evolve into typical and atypical targetoid lesions. Lesions evolve in 48-72 hours, favoring acrofacial sites that then spread down towards the trunk. Systemic symptoms such as fever and arthralgia may accompany the skin lesions.^1-3

Erythema multiforme is recognized in two forms: EM minor and EM major. Both forms share the same characteristic of target lesions. However, the presence of mucosal involvement distinguishes the two. Mucosal involvement is absent or mild in EM minor, while mucosal involvement in EM major is often severe.^2,3 Painful bullous lesions are commonly present in the mouth, genital, and ocular mucous membranes. Severe symptoms can often result in difficulty eating and drinking.

Diagnosis is largely clinical. Further histologic study may accompany diagnoses to exclude differential diagnosis. In EM, direct immunofluorescence (DIF) is negative. Histopathology reveals apoptosis of individual keratinocytes.^1,2

Therapeutic treatment for painful bullous lesions in the mouth involve antiseptic rinses and anesthetic solutions. Preventive treatment for patients with HSV-associated EM recurrence includes oral acyclovir or valacyclovir.²

In this patient, a punch biopsy was performed, confirming the diagnosis. A DIF was negative, and a chest x-ray was negative. Treatment was initiated with oral acyclovir, doxycycline, and a prednisone taper. In addition, topical clobetasol propionate and magic mouthwash (Maalox/lidocaine/nystatin) was prescribed. The patient was placed on daily suppressive valacyclovir to prevent frequent recurrence of EM.

This case and photo were submitted by Ms. Pham, the University of California, Los Angeles, and Dr. Sateesh, San Diego Family Dermatology. Dr. Bilu-Martin edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Hafsi W and Badri T. Erythema Multiforme, in “StatPearls [Internet].” Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

2. Bolognia J et al. Dermatology. St. Louis: Mosby/Elsevier, 2008.

3. Oakley A. Erythema Multiforme. DermNet NZ. 2015 Oct.

Erythema multiforme (EM) is a hypersensitivity reaction commonly caused by herpes simplex virus (HSV) infection. Less frequently observable infectious agents associated with EM are Mycoplasma pneumoniae, Histoplasma capsulatum, and parapoxvirus (orf). Rarely, EM is triggered by drug eruption or systemic disease. Individuals of all age groups and races can be affected by EM. However, it is predominantly observed in young adult patients (20-40 years of age), and there is a male predominance.

Patients typically present with the abrupt onset of symmetrical red papules that evolve into typical and atypical targetoid lesions. Lesions evolve in 48-72 hours, favoring acrofacial sites that then spread down towards the trunk. Systemic symptoms such as fever and arthralgia may accompany the skin lesions.^1-3

Erythema multiforme is recognized in two forms: EM minor and EM major. Both forms share the same characteristic of target lesions. However, the presence of mucosal involvement distinguishes the two. Mucosal involvement is absent or mild in EM minor, while mucosal involvement in EM major is often severe.^2,3 Painful bullous lesions are commonly present in the mouth, genital, and ocular mucous membranes. Severe symptoms can often result in difficulty eating and drinking.

Diagnosis is largely clinical. Further histologic study may accompany diagnoses to exclude differential diagnosis. In EM, direct immunofluorescence (DIF) is negative. Histopathology reveals apoptosis of individual keratinocytes.^1,2

Therapeutic treatment for painful bullous lesions in the mouth involve antiseptic rinses and anesthetic solutions. Preventive treatment for patients with HSV-associated EM recurrence includes oral acyclovir or valacyclovir.²

In this patient, a punch biopsy was performed, confirming the diagnosis. A DIF was negative, and a chest x-ray was negative. Treatment was initiated with oral acyclovir, doxycycline, and a prednisone taper. In addition, topical clobetasol propionate and magic mouthwash (Maalox/lidocaine/nystatin) was prescribed. The patient was placed on daily suppressive valacyclovir to prevent frequent recurrence of EM.

This case and photo were submitted by Ms. Pham, the University of California, Los Angeles, and Dr. Sateesh, San Diego Family Dermatology. Dr. Bilu-Martin edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Hafsi W and Badri T. Erythema Multiforme, in “StatPearls [Internet].” Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

2. Bolognia J et al. Dermatology. St. Louis: Mosby/Elsevier, 2008.

3. Oakley A. Erythema Multiforme. DermNet NZ. 2015 Oct.

Erythema multiforme (EM) is a hypersensitivity reaction commonly caused by herpes simplex virus (HSV) infection. Less frequently observable infectious agents associated with EM are Mycoplasma pneumoniae, Histoplasma capsulatum, and parapoxvirus (orf). Rarely, EM is triggered by drug eruption or systemic disease. Individuals of all age groups and races can be affected by EM. However, it is predominantly observed in young adult patients (20-40 years of age), and there is a male predominance.

Patients typically present with the abrupt onset of symmetrical red papules that evolve into typical and atypical targetoid lesions. Lesions evolve in 48-72 hours, favoring acrofacial sites that then spread down towards the trunk. Systemic symptoms such as fever and arthralgia may accompany the skin lesions.^1-3

Erythema multiforme is recognized in two forms: EM minor and EM major. Both forms share the same characteristic of target lesions. However, the presence of mucosal involvement distinguishes the two. Mucosal involvement is absent or mild in EM minor, while mucosal involvement in EM major is often severe.^2,3 Painful bullous lesions are commonly present in the mouth, genital, and ocular mucous membranes. Severe symptoms can often result in difficulty eating and drinking.

Diagnosis is largely clinical. Further histologic study may accompany diagnoses to exclude differential diagnosis. In EM, direct immunofluorescence (DIF) is negative. Histopathology reveals apoptosis of individual keratinocytes.^1,2

Therapeutic treatment for painful bullous lesions in the mouth involve antiseptic rinses and anesthetic solutions. Preventive treatment for patients with HSV-associated EM recurrence includes oral acyclovir or valacyclovir.²

In this patient, a punch biopsy was performed, confirming the diagnosis. A DIF was negative, and a chest x-ray was negative. Treatment was initiated with oral acyclovir, doxycycline, and a prednisone taper. In addition, topical clobetasol propionate and magic mouthwash (Maalox/lidocaine/nystatin) was prescribed. The patient was placed on daily suppressive valacyclovir to prevent frequent recurrence of EM.

This case and photo were submitted by Ms. Pham, the University of California, Los Angeles, and Dr. Sateesh, San Diego Family Dermatology. Dr. Bilu-Martin edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Hafsi W and Badri T. Erythema Multiforme, in “StatPearls [Internet].” Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

2. Bolognia J et al. Dermatology. St. Louis: Mosby/Elsevier, 2008.

3. Oakley A. Erythema Multiforme. DermNet NZ. 2015 Oct.