Dermatology

A 23-year-old woman with systemic lupus erythematosus (SLE) and a history of poor adherence to recommended treatment presented with a widespread pruritic rash and diffuse hair loss. The rash had rapidly progressed following sun exposure during the summer. The patient cited her mental health status (anxiety, depression), socioeconomic factors, and challenges with prescription insurance coverage as reasons for nonadherence to treatment.

Clinical examination revealed diffuse scarring alopecia and abnormal pigmentation of the scalp (FIGURE 1A), as well as large, red-brown, scaly, atrophic plaques on the face, ears, extremities, back, and buttocks (FIGURES 1B and 1C).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Generalized chronic cutaneouslupus erythematosus

The clinical features of our patient were most consistent with generalized chronic cutaneous lupus erythematosus (CCLE), which is 1 of 3 subtypes of cutaneous lupus erythematosus (CLE). The other 2 are acute and subacute cutaneous lupus erythematosus (ACLE and SCLE, respectively). CCLE is further divided into 3 distinct entities: discoid lupus erythematosus (DLE), chilblain lupus erythematosus, and lupus erythematosus panniculitis.

A negative ANA should not rule out the possibility of cutaneous lupus erythematosus.

Distinguishing between the different forms of cutaneous lupus can be challenging; diagnosis is based on differences in clinical features and duration of skin changes, as well as biopsy and lab results.¹ The clinical features of our patient were most consistent with DLE, based on the scarring alopecia with scaly atrophic plaques, dyspigmentation, and exacerbation following sun exposure.

DLE is the most common form of CCLE and frequently manifests in a localized, photosensitive distribution involving the scalp, ears, and/or face.² Less commonly, it can demonstrate a more generalized distribution involving the trunk and/or extremities (reported incidence of 1.04 per 100,000 people).³ Longstanding DLE lesions commonly exhibit scarring and dyspigmentation. DLE occurs in approximately 15% to 30% of SLE patients,⁴ whereas about 10% of patients with DLE will progress to SLE.³

Positive antinuclear antibodies (ANA) are found in 54% of patients with CCLE, compared to 74% and 81% of patients with SCLE and ACLE, respectively.⁵ Thus, a negative ANA should not rule out the possibility of CLE.

Comprehensive lab work and biopsy could expose a systemic origin

While our patient already had a diagnosis of SLE, many patients will present with no prior history of autoimmune connective tissue disease, and, in that case, the objective should be to confirm the diagnosis and evaluate for systemic involvement. This includes a thorough review of systems; skin biopsy; complete blood count; liver function tests; urinalysis; and measurement of creatinine, inflammatory markers, ANA, extractable nuclear antigens, double-stranded DNA, complement levels (C3, C4, total), and antiphospholipid antibodies.⁶

Continue to: Biopsy

Biopsy features of DLE include vacuolar interface dermatitis, basement membrane zone thickening, follicular plugging, superficial and deep perivascular and periadnexal lymphohistiocytic inflammation with plasma cells, and increased mucin deposition. Direct immunofluorescence biopsy may show a continuous granular immunoglobulin (Ig) G/IgA/IgM and C3 band at the basement membrane zone.

Abnormal serologic tests may support the diagnosis of SLE based on American College of Rheumatology criteria and could suggest additional organ involvement or associated conditions, such as lupus nephritis or antiphospholipid syndrome (respectively). Currently, no clear consensus exists on monitoring patients with cutaneous lupus for systemic disease.

A gamut of skin-changing conditions should be considered

The differential diagnosis in this case includes SCLE, dermatitis, tinea corporis, cutaneous drug eruptions, and graft-versus-host disease (GVHD).

SCLE classically manifests with annular or psoriasiform lesions on the sun-exposed areas of the upper trunk (eg, the chest, neck, and upper extremities), while the central face and scalp are typically spared. Differentiating between generalized DLE and SCLE may be the most difficult, given similarities in the associated skin changes.

Dermatitis (atopic or contact) manifests as pruritic erythematous eczematous plaques, most commonly involving the flexural areas in atopic dermatitis and an exposure-dependent distribution pattern in contact dermatitis. The patient may have a history of atopy.

Continue to: Tinea corporis

Tinea corporis will manifest with annular scaly patches or plaques and may demonstrate erythematous papules around hair follicles in Majocchi granuloma. A positive potassium hydroxide exam demonstrating fungal hyphae confirms the diagnosis.

Cutaneous drug eruptions can have various morphologies and timing of onset. Certain photosensitive drug reactions can be triggered or exacerbated with sun exposure. Therefore, it is necessary to obtain a thorough medication history, including any new medications that were started within the past 4 to 6 weeks, although onset can be delayed beyond this timeframe.

GVHD is a complication that more commonly follows allogeneic hematopoietic stem cell transplants, although it may be seen following solid-organ transplantation or transfusion of nonirradiated blood. Chronic GVHD has an onset ≥ 100 days after transplant and is divided into nonsclerotic (lichenoid, atopic dermatitis-like, psoriasiform, poikilodermatous) and sclerotic morphologies.

Successful Tx requires adherence but may not prevent flare-ups

First-line treatment options for severe and widespread skin manifestations of CLE include photoprotection, smoking cessation, topical corticosteroids, hydroxychloroquine, and systemic corticosteroids. Second-line treatments include chloroquine, methotrexate, or mycophenolate mofetil; thalidomide or lenalidomide may be considered for patients with refractory disease.^7,8

With successful treatment and photoprotection, patients may achieve significant skin clearing. Occasional flares, especially during warmer months, may occur if they are not diligent about photoprotection. Systemic treatments will also improve the patient’s systemic symptoms if the patient has concomitant SLE.

Our patient was advised to use topical steroids and to restart hydroxychloroquine 300 mg/d and mycophenolate mofetil 1000 mg/d (a regimen with which she had previously been nonadherent). The patient followed up with her family physician for assessment of her other medical issues. No new interventions for her mental health were initiated during this visit, as the severity of her depression was considered mild. She was referred to a case manager to navigate multiple medical appointments and prescription insurance coverage issues. The patient’s dose of mycophenolate mofetil was increased gradually to 3 g/d, and the patient experienced improvement in both her cutaneous lesions and systemic symptoms.

A 23-year-old woman with systemic lupus erythematosus (SLE) and a history of poor adherence to recommended treatment presented with a widespread pruritic rash and diffuse hair loss. The rash had rapidly progressed following sun exposure during the summer. The patient cited her mental health status (anxiety, depression), socioeconomic factors, and challenges with prescription insurance coverage as reasons for nonadherence to treatment.

Clinical examination revealed diffuse scarring alopecia and abnormal pigmentation of the scalp (FIGURE 1A), as well as large, red-brown, scaly, atrophic plaques on the face, ears, extremities, back, and buttocks (FIGURES 1B and 1C).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Generalized chronic cutaneouslupus erythematosus

The clinical features of our patient were most consistent with generalized chronic cutaneous lupus erythematosus (CCLE), which is 1 of 3 subtypes of cutaneous lupus erythematosus (CLE). The other 2 are acute and subacute cutaneous lupus erythematosus (ACLE and SCLE, respectively). CCLE is further divided into 3 distinct entities: discoid lupus erythematosus (DLE), chilblain lupus erythematosus, and lupus erythematosus panniculitis.

A negative ANA should not rule out the possibility of cutaneous lupus erythematosus.

Distinguishing between the different forms of cutaneous lupus can be challenging; diagnosis is based on differences in clinical features and duration of skin changes, as well as biopsy and lab results.¹ The clinical features of our patient were most consistent with DLE, based on the scarring alopecia with scaly atrophic plaques, dyspigmentation, and exacerbation following sun exposure.

DLE is the most common form of CCLE and frequently manifests in a localized, photosensitive distribution involving the scalp, ears, and/or face.² Less commonly, it can demonstrate a more generalized distribution involving the trunk and/or extremities (reported incidence of 1.04 per 100,000 people).³ Longstanding DLE lesions commonly exhibit scarring and dyspigmentation. DLE occurs in approximately 15% to 30% of SLE patients,⁴ whereas about 10% of patients with DLE will progress to SLE.³

Positive antinuclear antibodies (ANA) are found in 54% of patients with CCLE, compared to 74% and 81% of patients with SCLE and ACLE, respectively.⁵ Thus, a negative ANA should not rule out the possibility of CLE.

Comprehensive lab work and biopsy could expose a systemic origin

While our patient already had a diagnosis of SLE, many patients will present with no prior history of autoimmune connective tissue disease, and, in that case, the objective should be to confirm the diagnosis and evaluate for systemic involvement. This includes a thorough review of systems; skin biopsy; complete blood count; liver function tests; urinalysis; and measurement of creatinine, inflammatory markers, ANA, extractable nuclear antigens, double-stranded DNA, complement levels (C3, C4, total), and antiphospholipid antibodies.⁶

Continue to: Biopsy

Biopsy features of DLE include vacuolar interface dermatitis, basement membrane zone thickening, follicular plugging, superficial and deep perivascular and periadnexal lymphohistiocytic inflammation with plasma cells, and increased mucin deposition. Direct immunofluorescence biopsy may show a continuous granular immunoglobulin (Ig) G/IgA/IgM and C3 band at the basement membrane zone.

Abnormal serologic tests may support the diagnosis of SLE based on American College of Rheumatology criteria and could suggest additional organ involvement or associated conditions, such as lupus nephritis or antiphospholipid syndrome (respectively). Currently, no clear consensus exists on monitoring patients with cutaneous lupus for systemic disease.

A gamut of skin-changing conditions should be considered

The differential diagnosis in this case includes SCLE, dermatitis, tinea corporis, cutaneous drug eruptions, and graft-versus-host disease (GVHD).

SCLE classically manifests with annular or psoriasiform lesions on the sun-exposed areas of the upper trunk (eg, the chest, neck, and upper extremities), while the central face and scalp are typically spared. Differentiating between generalized DLE and SCLE may be the most difficult, given similarities in the associated skin changes.

Dermatitis (atopic or contact) manifests as pruritic erythematous eczematous plaques, most commonly involving the flexural areas in atopic dermatitis and an exposure-dependent distribution pattern in contact dermatitis. The patient may have a history of atopy.

Continue to: Tinea corporis

Tinea corporis will manifest with annular scaly patches or plaques and may demonstrate erythematous papules around hair follicles in Majocchi granuloma. A positive potassium hydroxide exam demonstrating fungal hyphae confirms the diagnosis.

Cutaneous drug eruptions can have various morphologies and timing of onset. Certain photosensitive drug reactions can be triggered or exacerbated with sun exposure. Therefore, it is necessary to obtain a thorough medication history, including any new medications that were started within the past 4 to 6 weeks, although onset can be delayed beyond this timeframe.

GVHD is a complication that more commonly follows allogeneic hematopoietic stem cell transplants, although it may be seen following solid-organ transplantation or transfusion of nonirradiated blood. Chronic GVHD has an onset ≥ 100 days after transplant and is divided into nonsclerotic (lichenoid, atopic dermatitis-like, psoriasiform, poikilodermatous) and sclerotic morphologies.

Successful Tx requires adherence but may not prevent flare-ups

First-line treatment options for severe and widespread skin manifestations of CLE include photoprotection, smoking cessation, topical corticosteroids, hydroxychloroquine, and systemic corticosteroids. Second-line treatments include chloroquine, methotrexate, or mycophenolate mofetil; thalidomide or lenalidomide may be considered for patients with refractory disease.^7,8

With successful treatment and photoprotection, patients may achieve significant skin clearing. Occasional flares, especially during warmer months, may occur if they are not diligent about photoprotection. Systemic treatments will also improve the patient’s systemic symptoms if the patient has concomitant SLE.

Our patient was advised to use topical steroids and to restart hydroxychloroquine 300 mg/d and mycophenolate mofetil 1000 mg/d (a regimen with which she had previously been nonadherent). The patient followed up with her family physician for assessment of her other medical issues. No new interventions for her mental health were initiated during this visit, as the severity of her depression was considered mild. She was referred to a case manager to navigate multiple medical appointments and prescription insurance coverage issues. The patient’s dose of mycophenolate mofetil was increased gradually to 3 g/d, and the patient experienced improvement in both her cutaneous lesions and systemic symptoms.

A 23-year-old woman with systemic lupus erythematosus (SLE) and a history of poor adherence to recommended treatment presented with a widespread pruritic rash and diffuse hair loss. The rash had rapidly progressed following sun exposure during the summer. The patient cited her mental health status (anxiety, depression), socioeconomic factors, and challenges with prescription insurance coverage as reasons for nonadherence to treatment.

Clinical examination revealed diffuse scarring alopecia and abnormal pigmentation of the scalp (FIGURE 1A), as well as large, red-brown, scaly, atrophic plaques on the face, ears, extremities, back, and buttocks (FIGURES 1B and 1C).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Dx: Generalized chronic cutaneouslupus erythematosus

The clinical features of our patient were most consistent with generalized chronic cutaneous lupus erythematosus (CCLE), which is 1 of 3 subtypes of cutaneous lupus erythematosus (CLE). The other 2 are acute and subacute cutaneous lupus erythematosus (ACLE and SCLE, respectively). CCLE is further divided into 3 distinct entities: discoid lupus erythematosus (DLE), chilblain lupus erythematosus, and lupus erythematosus panniculitis.

A negative ANA should not rule out the possibility of cutaneous lupus erythematosus.

Distinguishing between the different forms of cutaneous lupus can be challenging; diagnosis is based on differences in clinical features and duration of skin changes, as well as biopsy and lab results.¹ The clinical features of our patient were most consistent with DLE, based on the scarring alopecia with scaly atrophic plaques, dyspigmentation, and exacerbation following sun exposure.

DLE is the most common form of CCLE and frequently manifests in a localized, photosensitive distribution involving the scalp, ears, and/or face.² Less commonly, it can demonstrate a more generalized distribution involving the trunk and/or extremities (reported incidence of 1.04 per 100,000 people).³ Longstanding DLE lesions commonly exhibit scarring and dyspigmentation. DLE occurs in approximately 15% to 30% of SLE patients,⁴ whereas about 10% of patients with DLE will progress to SLE.³

Positive antinuclear antibodies (ANA) are found in 54% of patients with CCLE, compared to 74% and 81% of patients with SCLE and ACLE, respectively.⁵ Thus, a negative ANA should not rule out the possibility of CLE.

Comprehensive lab work and biopsy could expose a systemic origin

While our patient already had a diagnosis of SLE, many patients will present with no prior history of autoimmune connective tissue disease, and, in that case, the objective should be to confirm the diagnosis and evaluate for systemic involvement. This includes a thorough review of systems; skin biopsy; complete blood count; liver function tests; urinalysis; and measurement of creatinine, inflammatory markers, ANA, extractable nuclear antigens, double-stranded DNA, complement levels (C3, C4, total), and antiphospholipid antibodies.⁶

Continue to: Biopsy

Biopsy features of DLE include vacuolar interface dermatitis, basement membrane zone thickening, follicular plugging, superficial and deep perivascular and periadnexal lymphohistiocytic inflammation with plasma cells, and increased mucin deposition. Direct immunofluorescence biopsy may show a continuous granular immunoglobulin (Ig) G/IgA/IgM and C3 band at the basement membrane zone.

Abnormal serologic tests may support the diagnosis of SLE based on American College of Rheumatology criteria and could suggest additional organ involvement or associated conditions, such as lupus nephritis or antiphospholipid syndrome (respectively). Currently, no clear consensus exists on monitoring patients with cutaneous lupus for systemic disease.

A gamut of skin-changing conditions should be considered

The differential diagnosis in this case includes SCLE, dermatitis, tinea corporis, cutaneous drug eruptions, and graft-versus-host disease (GVHD).

SCLE classically manifests with annular or psoriasiform lesions on the sun-exposed areas of the upper trunk (eg, the chest, neck, and upper extremities), while the central face and scalp are typically spared. Differentiating between generalized DLE and SCLE may be the most difficult, given similarities in the associated skin changes.

Dermatitis (atopic or contact) manifests as pruritic erythematous eczematous plaques, most commonly involving the flexural areas in atopic dermatitis and an exposure-dependent distribution pattern in contact dermatitis. The patient may have a history of atopy.

Continue to: Tinea corporis

Tinea corporis will manifest with annular scaly patches or plaques and may demonstrate erythematous papules around hair follicles in Majocchi granuloma. A positive potassium hydroxide exam demonstrating fungal hyphae confirms the diagnosis.

Cutaneous drug eruptions can have various morphologies and timing of onset. Certain photosensitive drug reactions can be triggered or exacerbated with sun exposure. Therefore, it is necessary to obtain a thorough medication history, including any new medications that were started within the past 4 to 6 weeks, although onset can be delayed beyond this timeframe.

GVHD is a complication that more commonly follows allogeneic hematopoietic stem cell transplants, although it may be seen following solid-organ transplantation or transfusion of nonirradiated blood. Chronic GVHD has an onset ≥ 100 days after transplant and is divided into nonsclerotic (lichenoid, atopic dermatitis-like, psoriasiform, poikilodermatous) and sclerotic morphologies.

Successful Tx requires adherence but may not prevent flare-ups

First-line treatment options for severe and widespread skin manifestations of CLE include photoprotection, smoking cessation, topical corticosteroids, hydroxychloroquine, and systemic corticosteroids. Second-line treatments include chloroquine, methotrexate, or mycophenolate mofetil; thalidomide or lenalidomide may be considered for patients with refractory disease.^7,8

With successful treatment and photoprotection, patients may achieve significant skin clearing. Occasional flares, especially during warmer months, may occur if they are not diligent about photoprotection. Systemic treatments will also improve the patient’s systemic symptoms if the patient has concomitant SLE.

Our patient was advised to use topical steroids and to restart hydroxychloroquine 300 mg/d and mycophenolate mofetil 1000 mg/d (a regimen with which she had previously been nonadherent). The patient followed up with her family physician for assessment of her other medical issues. No new interventions for her mental health were initiated during this visit, as the severity of her depression was considered mild. She was referred to a case manager to navigate multiple medical appointments and prescription insurance coverage issues. The patient’s dose of mycophenolate mofetil was increased gradually to 3 g/d, and the patient experienced improvement in both her cutaneous lesions and systemic symptoms.

PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.

Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.

“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.

At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.

The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.

Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”

To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”

In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.

The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.

But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.

On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.

Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”

Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”

The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”

Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”

Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.

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

PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.

Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.

“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.

At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.

The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.

Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”

To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”

In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.

The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.

But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.

On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.

Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”

Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”

The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”

Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”

Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.

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

PHOENIX – For at least a decade, professional allergy and pediatrics societies have urged against using food IgE tests unless the patient has a history consistent with potential IgE-mediated food allergies. Yet virtually every health system offers these blood tests, and their inappropriate use – especially of panels that measure many allergens at once – remains a huge problem.

Beyond wasteful spending, excessive food IgE testing can lead patients to worry needlessly and to avoid foods they aren’t allergic to. For babies and toddlers, avoidance can drive up the risk of developing allergies to those foods later in life – a consequence that was convincingly proven by the LEAP study but has still not translated to a widespread change in practice.

“I think we all know that there’s just a lot of system-wide resistance to making these changes, and we don’t completely understand why,” Nicholas Hartog, MD, an allergist with Spectrum Health in Grand Rapids, Mich., told this news organization.

At the American Academy of Allergy, Asthma & Immunology annual meeting, one of Dr. Hartog’s residents, Courtney Cotter, DO, presented a poster detailing their team’s retrospective review of food panel ordering practices across Spectrum Health, a large, multispecialty physician group in west Michigan.

The team combed Epic health records to evaluate food IgE ordering from January 2016 to December 2021. They tracked monthly figures for the number of patients who underwent food IgE tests, the percentage of tested patients for whom food panels were available, and the number of food panels and total number of food IgE tests ordered. They compared average rates from the final 3 months with rates from the first 3 months, which predated the August 2016 establishment of an academic pediatric allergy/immunology department.

Initially, Dr. Hartog and his colleagues focused on educating doctors on appropriate use of food IgE tests through informal conversations and lectures, but, he said, “It’s really difficult to change physician behavior, so sometimes we have to go about it by making it hard to do the wrong thing.”

To that end, the team tried to eliminate the food panels. However, some lab staff feared the possibility of losing revenue if physicians decided to order these tests elsewhere. After more negotiations, the laboratory agreed in December 2019 to restrict and rework food IgE testing by dropping the number of panels from nine to two and by restricting the number of foods in those panels. For example, in the basic panel, “we limited it to just four allergens, so even if you order a panel, you’re not getting 20 results,” Dr. Hartog told this news organization. “I finally found a friendly pathologist who was very on board with this positive change.”

In December 2020, the team implemented yet another strategy: Epic alerts. Each time doctors request a food panel, they receive a pop-up message stating that panel tests are not recommended and asking if they wish to proceed.

The multipronged effort had a modest impact on the number of food panels ordered per month, which dipped from 112.7 to 84.7 for the first and last 3 months of the study. Monthly totals of individual food IgE tests showed a steeper drop, decreasing from 2,379 to 1,180 in the initial and final 3-month periods – a change Dr. Hartog attributes to the revamped food panels. They estimated the cost savings at around $40 per patient, “and we were getting on average about 200 patients a month, so it adds up,” he said.

But the Epic alerts seemed to have little effect. Over the duration of the study, the monthly number of IgE tests ordered per clinician did not change. Neither did the percentage of patients evaluated with a food panel. “The alerts pop up, but people are still ordering,” Dr. Hartog said.

On the whole, the analysis shows that, “despite major efforts to educate providers and the public about these things, it is rampantly disregarded and is a huge problem for our specialty and is likely causing harm to patients,” said allergist-immunologist Gerald Lee, MD, of Emory University in Atlanta.

Dr. Lee said that a common scenario for inappropriate food IgE testing is severe eczema. Many parents request blood tests because they assume their child’s skin condition is driven by food allergies. When the child turns up positive to various foods on panel tests, which have high false-positive rates, the physician may recommend eliminating those foods to improve the skin rash – which “actually delays introduction of the food and potentially increases the risk for food allergy,” Dr. Lee said. “That was a common practice when I was in fellowship (2011) and is widely prevalent today.”

Edwin Kim, MD, director of the UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill, agrees that food IgE panels are wasteful and harmful. However, he thinks the solution is not to tell primary care physicians and pediatricians to stop using the tests. “We’re insinuating that they’re being used inappropriately, but the problem is that these are people that are patient facing, the patients are asking a question, and the appropriate tests aren’t there,” Dr. Kim said. “A big part of that problem is that the tests we have available to us are not good enough.”

The Spectrum Health analysis did not examine ICD codes associated with the food IgE tests or track which physicians ordered the tests. A 2016 retrospective review published in Pediatrics did evaluate ordering practices by specialty and found that primary care providers ordered “significantly more food allergen panels, tests for uncommon causes of food allergy, and generate higher cost per patient compared with allergists.”

Given the immense challenges with implementing system-wide changes, sometimes it can help to educate parents and families. “When you sit down and take 2 or 3 minutes to explain why this is a bad test and that I care about your kid but just don’t want inappropriate testing, they’re okay with it. They understand,” Dr. Hartog said. “When I teach residents, I make sure to emphasize that we have these conversations all the time.”

Dr. Hartog reports financial relationships with Binding Site (speaker), Regeneron (advisory board), Genentech (advisory board), Horizon Pharmaceuticals (advisory board, consulting, speaker), Takeda (speaker, advisory board) and Pharming Healthcare (advisory board, scientific steering committee, consulting), though none related to food allergy. Dr. Lee has disclosed no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network; the National Center for Complementary and Integrative Health; Food Allergy Research and Education; and the Wallace Research Foundation.

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

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

The Diagnosis: Bullous Pyoderma Gangrenosum

A bone marrow biopsy revealed 60% myeloblasts, leading to a diagnosis of acute myeloid leukemia (AML). A biopsy obtained from the edge of the bullous plaque demonstrated a dense dermal neutrophilic infiltrate with extravasated erythrocytes (Figure). Fite, Gram, and Grocott-Gomori methenamine-silver staining failed to reveal infectious organisms. Tissue and blood cultures were negative. Given the pathologic findings, clinical presentation including recent diagnosis of AML, and exclusion of other underlying disease processes including infection, the diagnosis of bullous pyoderma gangrenosum (PG) was made. The lesion improved with systemic steroids and treatment of the underlying AML with fludarabine and venetoclax chemotherapy.

First recognized in 1916 by French dermatologist Louis Brocq, MD, PG is a sterile neutrophilic dermatosis that predominantly affects women older than 50 years.^1,2 This disorder can develop idiopathically; secondary to trauma; or in association with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, and hematologic malignancies. The pathogenesis of PG remains unclear; however, overexpression of inflammatory cytokines may mediate its development by stimulating T cells and promoting neutrophilic chemotaxis.³

Pyoderma gangrenosum classically presents as a rapidly enlarging ulcer with cribriform scarring but manifests variably. Four variants of the disorder exist: classic ulcerative, pustular, bullous, and vegetative PG. Ulcerative PG is the most common variant. Bullous PG is associated with hematologic malignancies such as primary myelofibrosis, myelodysplastic disease, and AML. In these patients, hematologic malignancy often exists prior to the development of PG and portends a poorer prognosis. This association underscores the importance of timely diagnosis and thorough hematologic evaluation by obtaining a complete blood cell count with differential, peripheral smear, serum protein electrophoresis with immunofixation, and quantitative immunoglobulins (IgA, IgG, IgM). If any of the results are positive, prompt referral to a hematologist and bone marrow biopsy are paramount.³

The diagnosis of PG remains elusive, as no validated clinical or pathological criteria exist. Histopathologic evaluation may be nonspecific and variable depending on the subtype. Biopsy results for classic ulcerative PG may reveal a neutrophilic infiltrate with leukocytoclasia. Bullous PG may include subepidermal hemorrhagic bullae. Notably, bullous PG appears histologically similar to the superficial bullous variant of Sweet syndrome.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a type of neutrophilic dermatosis characterized by fever, neutrophilia, and the sudden onset of tender erythematous lesions. Variations include idiopathic, subcutaneous, and bullous Sweet syndrome, which present as plaques, nodules, or bullae, respectively.⁴ Similar to PG, Sweet syndrome can manifest in patients with hematologic malignancies. Both PG and Sweet syndrome are thought to exist along a continuum and can be considered intersecting diagnoses in the setting of leukemia or other hematologic malignancies.⁵ There have been reports of the coexistence of distinct PG and Sweet syndrome lesions on a single patient, further supporting the belief that these entities share a common pathologic mechanism.⁶ Sweet syndrome also commonly can be associated with upper respiratory infections; pregnancy; and medications, with culprits including granulocyte colony-stimulating factor, azathioprine, vemurafenib, and isotretinoin.⁷

Other differential diagnoses include brown recluse spider bite, bullous fixed drug eruption (FDE), and necrotizing fasciitis (NF). Venom from the brown recluse spider (Loxosceles reclusa) can trigger toxin-mediated hemolysis, complement-mediated erythrocyte destruction, and basement membrane zone degradation due to the synergistic effects of the toxin’s sphingomyelinase D and protease content.⁸ The inciting bite is painless. After 8 hours, the site becomes painful and pruritic and presents with peripheral erythema and central pallor. After 24 hours, the lesion blisters. The blister ruptures within 3 to 4 days, resulting in eschar formation with the subsequent development of an indurated blue ulcer with a stellate center. Ulcers can take months to heal.⁹ Based on the clinical findings in our patient, this diagnosis was less likely.

Fixed drug eruption is a localized cutaneous reaction that manifests in fixed locations minutes to days after exposure to medications such as trimethoprimsulfamethoxazole, nonsteroidal anti-inflammatory drugs, salicylates, and oral contraceptives. Commonly affected areas include the hands, legs, genitals, and trunk. Lesions initially present as well-demarcated, erythematous to violaceous, round plaques. A rarer variant manifesting as bullae also has been described. Careful consideration of the patient’s history and physical examination findings is sufficient for establishing this diagnosis; however, a punch biopsy can provide clarity. Histopathology reveals a lichenoid tissue reaction with dyskeratosis, broad epidermal necrosis, and damage to the stratum basalis. A lymphocytic perivascular infiltrate also may appear in the dermis.¹⁰ Both the clinical findings and histopathology of our case were not characteristic of FDE.

Necrotizing fasciitis is a fulminant, life-threatening, soft-tissue infection precipitated by polymicrobial flora. Early recognition of NF is difficult, as in its early stages it can mimic cellulitis. As the infection takes its course, necrosis can extend from the skin and into the subcutaneous tissue. Patients also develop fever, leukocytosis, and signs of sepsis. Histopathology demonstrates neutrophilic infiltration with bacterial invasion as well as necrosis of the superficial fascia and subepidermal edema.¹¹ Pyoderma gangrenosum previously has been reported to mimic NF; however, lack of responsiveness to antibiotic therapy would favor a diagnosis of PG over NF.¹²

Treatment of PG is driven by the extent of cutaneous involvement. In mild cases, wound care and topical therapy with corticosteroids and tacrolimus may suffice. Severe cases necessitate systemic therapy with oral corticosteroids or cyclosporine; biologic therapy also may play a role in treatment.⁴ In patients with hematologic malignancy, chemotherapy alone may partially or completely resolve the lesion; however, systemic corticosteroids commonly are included in management.³

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

TikTok users seeking deep tans are employing a questionable method: spraying self-tanning products up their noses, and then laying out in the sun or in a tanning bed.

Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.

The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.

“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”

Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.

The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.

In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.

But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.

“Don’t try this at home,” said Dr. Talakoub.

“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”

It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.

Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”

@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.

TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.

The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.

“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.

“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.

“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”

At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.

Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.

“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”

He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.

“At the end of the day, just don’t inhale,” Dr. Friedman said.

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

TikTok users seeking deep tans are employing a questionable method: spraying self-tanning products up their noses, and then laying out in the sun or in a tanning bed.

Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.

The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.

“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”

Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.

The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.

In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.

But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.

“Don’t try this at home,” said Dr. Talakoub.

“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”

It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.

Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”

@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.

TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.

The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.

“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.

“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.

“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”

At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.

Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.

“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”

He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.

“At the end of the day, just don’t inhale,” Dr. Friedman said.

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

TikTok users seeking deep tans are employing a questionable method: spraying self-tanning products up their noses, and then laying out in the sun or in a tanning bed.

Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.

The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.

“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”

Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.

The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.

In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.

But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.

“Don’t try this at home,” said Dr. Talakoub.

“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”

It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.

Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”

@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.

TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.

The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.

“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.

“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.

“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”

At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.

Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.

“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”

He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.

“At the end of the day, just don’t inhale,” Dr. Friedman said.

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

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

The rate of recurrence of the rare but aggressive skin cancer Merkel cell carcinoma (MCC) is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma, and more than half of all patients with stage IV disease will have a recurrence within 1 year of definitive therapy, results of a new study show.

A study of 618 patients with MCC who were enrolled in a Seattle-based data repository shows that among all patients the 5-year recurrence rate was 40%. The risk of recurrence within the first year was 11% for patients with pathologic stage I disease, 33% for those with stage IIA/IIB disease, 45% for those with stage IIIB disease, and 58% for patients with pathologic stage IV MCC.

Approximately 95% of all recurrences happened within 3 years of the initial diagnosis, report Aubriana McEvoy, MD, from the University of Washington in Seattle, and colleagues.

“This cohort study indicates that the highest yield (and likely most cost-effective) time period for detecting MCC recurrence is 1-3 years after diagnosis,” they write in a study published online in JAMA Dermatology.

The estimated annual incidence of MCC in the United States in 2018 was 2,000 according to the American Cancer Society. The annual incidence rate is rising rapidly, however, and is estimated to reach 3,284 by 2025, McEvoy and colleagues write.

Although MCC is known to have high recurrence rates and is associated with a higher mortality rate than malignant melanoma, recurrence rate data are not captured by either the Surveillance, Epidemiology, and End Results (SEER) database or by the National Cancer Database. As a result, estimates of recurrence rates with MCC have been all over the map, ranging from 27% to 77%, depending on the population studied.

But as senior author Paul Nghiem, MD, PhD, professor and chair of dermatology at the University of Washington, Seattle, told this news organization, recurrence rates over time in their study were remarkably consistent.

“The biggest surprise to me was that, when we broke our nearly 20-year cohort into three 5- or 6-year chunks, every one of the groups had a 40% recurrence rate, within 1%. So we feel really confident that’s the right number,” he said.

Dr. Nghiem and colleagues report that, in contrast to patients with MCC, approximately 19% of patients with melanoma will have a recurrence, as will an estimated 5%-9% of patients with squamous cell carcinoma and 1%-10% of patients with basal cell carcinoma.

The fact that recurrence rates of MCC have remained stable over time despite presumed improvements in definitive therapy is disappointing, Dr. Nghiem acknowledged. He noted that it’s still unclear whether immunotherapy will have the same dramatic effect on survival rates for patients with MCC as it has for patients with malignant melanoma.

The high recurrence rates following definitive therapy for patients with early-stage disease was a novel finding, commented Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at Massachusetts General Hospital in Boston.

“When you’re looking at patients with stage I or stage II, and they have definitive surgery but still have recurrences at a higher rate than melanoma, it brings home the point that these are among the most aggressive tumors of the skin,” he said in an interview.

The high recurrence rates seen with MCC are attributable to a variety of factors.

“This is a rare cancer of mostly older individuals with a lot of comorbidities, and also a cancer that, even though it is a primary cancer, might be detected a little later than even a melanoma primary tumor, just because of the nature of the neuroendocrine tumor cells,” he said.

Dr. Demehri was not involved in the study.
 

Prospective cohort

The study cohort consisted of 618 patients with MCC. The median age of the patients was 69, and 227 (37%) were women. The patients were enrolled within 6 months of their diagnosis in the prospective data repository from 2003 through 2019. Of this group, 223 had a recurrence of MCC.

As noted, there was a high risk of recurrence within 1 year, ranging from 11% for patients with pathologic stage I tumors to 58% for those with stage IV disease, and 95% of all recurrences occurred within 3 years of definitive therapy.

To get a better picture of the natural history of MCC recurrence, the investigators studied a cohort of patients with pathologically confirmed MCC who were prospectively enrolled from January 2003 through April 2019 in a data repository maintained at the University of Washington.

In addition to disease stage, factors associated with increased recurrence risk in univariable analyses include immunosuppression (hazard ratio, 2.4; P < .001), male sex (HR, 1.9; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; P = .001), and older age (HR, 1.1, P = .06 for each 10-year increase).

Of the 187 patients in the cohort who died during the study, 121 died from MCC. At 4 years after diagnosis, MCC-specific survival rates were 95% for patients with pathologic stage I, 84% with stage IIA/IIB, 80% with stage IIIA, 58% with stage IIIB, and 41% with stage IV.

Evidence supports close monitoring within the first 3 years for patients with stage I-II MCC. Local recurrence within or adjacent to the primary tumor scar was associated with a 5-year MCC-specific survival rate of 85%, compared with 88% of patients with stage I or II disease who did not have recurrences.

“Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest,” the authors wrote.

“If you’re a patient who has not had your cancer come back for 3, 4, or 5 years, you can really cut down on the intensity of your follow-up and scans,” Dr. Nghiem said.

“We do now have two excellent blood tests that are working very well, and we have really good ways to detect the cancer coming back early, and that’s important, because we have potentially curative therapies that tend to work better if you catch the cancer early,” he said.

The study was supported by the National Institutes of Health. Dr. Nghiem reported personal fees and institutional support outside the study from several companies and patents for Merkel cell therapies with the University of Washington and University of Denmark. Dr. Demehri has disclosed no relevant financial relationships.

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

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.