Dermatology

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.

No such action has been taken in the United States.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.

“While uncertainties remain, there is concern about a possible link between the use of Picato and the development of skin cancer,” the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”

FDA is looking at the situation

LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.

“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.

The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.

Examining the data

The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.

In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).

In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.

“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.

Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.

[email protected]

As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.

No such action has been taken in the United States.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.

“While uncertainties remain, there is concern about a possible link between the use of Picato and the development of skin cancer,” the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”

FDA is looking at the situation

LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.

“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.

The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.

Examining the data

The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.

In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).

In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.

“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.

Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.

[email protected]

As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.

No such action has been taken in the United States.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.

“While uncertainties remain, there is concern about a possible link between the use of Picato and the development of skin cancer,” the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”

FDA is looking at the situation

LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.

“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.

The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.

Examining the data

The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.

In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).

In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.

“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.

Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.

[email protected]

Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at [email protected].

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at [email protected].

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at [email protected].

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

[email protected]

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

[email protected]

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

[email protected]

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The global prevalence of oral lichen planus just received its first-ever systematic review and meta-analysis, and the resulting estimates are 0.89% for the general population and 0.98% among clinical patients.

Globally, oral lichen planus (OLP) appears to be more prevalent in women than men (1.55% vs. 1.11% in population-based studies; 1.69% vs. 1.09% in clinic-based), in those aged 40 years and older (1.90% vs. 0.62% in clinic-based studies), and in non-Asian countries (see graph), Changchang Li, MD, and associates reported in JAMA Dermatology.

Of the 25 countries represented among the 46 included studies, Brazil had the highest OLP prevalence at 6.04% and India had the lowest at 0.02%. “Smokers and patients who abuse alcohol have a higher prevalence of OLP. This factor may explain why the highest prevalence … was found in Brazil, where 18.18% of residents report being smokers and 29.09% report consumption of alcoholic beverages,” wrote Dr. Li of the department of dermatology at Zhejiang University of Traditional Chinese Medicine, Wenzhou, China, and associates.

The difference in OLP prevalence by sex may be related to fluctuating female hormone levels, “especially during menstruation or menopause, and that different social roles may lead to the body being in a state of stress,” the investigators suggested.

The age-related difference in OLP could be the result of “longstanding oral habits” or changes to the oral mucosa over time, such as mucosal thinning, decreased elasticity, less saliva secretion, and greater tissue permeability. The higher prevalence among those aged 40 years and older also may be “associated with metabolic changes during aging or with decreased immunity, nutritional deficiencies, medication use, or denture wear,” they wrote.

The review and meta-analysis involved 15 studies (n = 462,993) that included general population data and 31 (n = 191,963) that used information from clinical patients. Sample sizes for those studies ranged from 308 to 402,669.

Statistically significant publication bias was seen among the clinic-based studies but not those that were population based, Dr. Li and associates wrote, adding that “our findings should be considered with caution because of the high heterogeneity of the included studies.”

The study was funded by the First-Class Discipline Construction Foundation of Guangzhou University of Chinese Medicine, the Young Top Talent Project of Scientific and Technological Innovation in Special Support Plan for Training High-level Talents, and the Youth Research and Cultivation Project of Guangzhou University of Chinese Medicine. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: C Li et al. JAMA Dermatol. 2020 Jan 2. doi: 10.1001/jamadermatol.2019.3797.

The global prevalence of oral lichen planus just received its first-ever systematic review and meta-analysis, and the resulting estimates are 0.89% for the general population and 0.98% among clinical patients.

Globally, oral lichen planus (OLP) appears to be more prevalent in women than men (1.55% vs. 1.11% in population-based studies; 1.69% vs. 1.09% in clinic-based), in those aged 40 years and older (1.90% vs. 0.62% in clinic-based studies), and in non-Asian countries (see graph), Changchang Li, MD, and associates reported in JAMA Dermatology.

Of the 25 countries represented among the 46 included studies, Brazil had the highest OLP prevalence at 6.04% and India had the lowest at 0.02%. “Smokers and patients who abuse alcohol have a higher prevalence of OLP. This factor may explain why the highest prevalence … was found in Brazil, where 18.18% of residents report being smokers and 29.09% report consumption of alcoholic beverages,” wrote Dr. Li of the department of dermatology at Zhejiang University of Traditional Chinese Medicine, Wenzhou, China, and associates.

The difference in OLP prevalence by sex may be related to fluctuating female hormone levels, “especially during menstruation or menopause, and that different social roles may lead to the body being in a state of stress,” the investigators suggested.

The age-related difference in OLP could be the result of “longstanding oral habits” or changes to the oral mucosa over time, such as mucosal thinning, decreased elasticity, less saliva secretion, and greater tissue permeability. The higher prevalence among those aged 40 years and older also may be “associated with metabolic changes during aging or with decreased immunity, nutritional deficiencies, medication use, or denture wear,” they wrote.

The review and meta-analysis involved 15 studies (n = 462,993) that included general population data and 31 (n = 191,963) that used information from clinical patients. Sample sizes for those studies ranged from 308 to 402,669.

Statistically significant publication bias was seen among the clinic-based studies but not those that were population based, Dr. Li and associates wrote, adding that “our findings should be considered with caution because of the high heterogeneity of the included studies.”

The study was funded by the First-Class Discipline Construction Foundation of Guangzhou University of Chinese Medicine, the Young Top Talent Project of Scientific and Technological Innovation in Special Support Plan for Training High-level Talents, and the Youth Research and Cultivation Project of Guangzhou University of Chinese Medicine. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: C Li et al. JAMA Dermatol. 2020 Jan 2. doi: 10.1001/jamadermatol.2019.3797.

The global prevalence of oral lichen planus just received its first-ever systematic review and meta-analysis, and the resulting estimates are 0.89% for the general population and 0.98% among clinical patients.

Globally, oral lichen planus (OLP) appears to be more prevalent in women than men (1.55% vs. 1.11% in population-based studies; 1.69% vs. 1.09% in clinic-based), in those aged 40 years and older (1.90% vs. 0.62% in clinic-based studies), and in non-Asian countries (see graph), Changchang Li, MD, and associates reported in JAMA Dermatology.

Of the 25 countries represented among the 46 included studies, Brazil had the highest OLP prevalence at 6.04% and India had the lowest at 0.02%. “Smokers and patients who abuse alcohol have a higher prevalence of OLP. This factor may explain why the highest prevalence … was found in Brazil, where 18.18% of residents report being smokers and 29.09% report consumption of alcoholic beverages,” wrote Dr. Li of the department of dermatology at Zhejiang University of Traditional Chinese Medicine, Wenzhou, China, and associates.

The difference in OLP prevalence by sex may be related to fluctuating female hormone levels, “especially during menstruation or menopause, and that different social roles may lead to the body being in a state of stress,” the investigators suggested.

The age-related difference in OLP could be the result of “longstanding oral habits” or changes to the oral mucosa over time, such as mucosal thinning, decreased elasticity, less saliva secretion, and greater tissue permeability. The higher prevalence among those aged 40 years and older also may be “associated with metabolic changes during aging or with decreased immunity, nutritional deficiencies, medication use, or denture wear,” they wrote.

The review and meta-analysis involved 15 studies (n = 462,993) that included general population data and 31 (n = 191,963) that used information from clinical patients. Sample sizes for those studies ranged from 308 to 402,669.

Statistically significant publication bias was seen among the clinic-based studies but not those that were population based, Dr. Li and associates wrote, adding that “our findings should be considered with caution because of the high heterogeneity of the included studies.”

The study was funded by the First-Class Discipline Construction Foundation of Guangzhou University of Chinese Medicine, the Young Top Talent Project of Scientific and Technological Innovation in Special Support Plan for Training High-level Talents, and the Youth Research and Cultivation Project of Guangzhou University of Chinese Medicine. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: C Li et al. JAMA Dermatol. 2020 Jan 2. doi: 10.1001/jamadermatol.2019.3797.

MADRID – European atopic dermatitis experts have issued formal guidance on a seriously neglected topic: treatment of the disease during pregnancy, breastfeeding, and in men planning to father children.

Bruce Jancin/MDedge News

The impetus for the project was clear: “Treatment of atopic dermatitis in pregnancy is often forgotten or even ignored,” Christian Vestergaard, MD, PhD, declared at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of the task force’s position paper on the topic, for which he served as first author. The group’s recommendations are based on expert opinion, since randomized clinical trial literature in this area is nonexistent because of ethical concerns. But the task force, comprising a who’s who in European dermatology, drew on a wealth of collective clinical experience in this area.

“We have all of Europe involved in doing this position statement. It’s meant as what we think is proper treatment and what we can say about the different drugs,” explained Dr. Vestergaard, a dermatologist at the University of Aarhus (Denmark).

Most nonobstetricians are intimidated by atopic dermatitis (AD) in pregnancy, and are concerned about the potential for treatment-related harm to the fetus. As a consequence, they are reluctant to recommend anything beyond weak class I topical corticosteroids and emollients. That’s clearly insufficient in light of the vast scope of need, he asserted. After all, AD affects 15%-20% of all children and persists or reappears in adulthood in one out of five of them. Half of those adults are women, many of whom will at some point wish to become pregnant. And many men with AD will eventually want to father children.

A key message from the task force is that untreated AD in pregnancy potentially places the mother and fetus at risk of serious complications, including Staphylococcus aureus infection and eczema herpeticum.

“If you take one thing away from our position paper, it’s that you can use class II or III topical corticosteroids in pregnant women as first-line therapy,” Dr. Vestergaard said.

This stance contradicts a longstanding widely held concern that topical steroids in pregnancy might increase the risk of facial cleft in the offspring, a worry that has been convincingly debunked in a Cochrane systematic review of 14 studies including more than 1.6 million pregnancies. The report concluded there was no association between topical corticosteroids of any potency with preterm delivery, birth defects, or low Apgar scores (Cochrane Database Syst Rev. 2015 Oct 26. doi: 10.1002/14651858.CD007346.pub3).

The task force recommends that if class II or III topical corticosteroid use in pregnancy exceeds 200 g/month, it’s worth considering add-on UV therapy, with narrow band UVB-311 nm as the regimen of choice; it can be used liberally. UV therapy with psoralens is not advised because of a theoretical risk of mutagenicity.

Product labeling for the topical calcineurin inhibitors declares that the agents should not be used during pregnancy. However, the European task force position paper takes issue with that and declares that topical tacrolimus (Protopic) can be considered an off-label first-line therapy in pregnant women with an insufficient response to liberal use of emollients. The same holds true for breastfeeding patients with AD. Just as when topical corticosteroids are used in the nipple area, topical tacrolimus should be applied after nursing, and the nipple area should be gently cleaned before nursing.

The rationale behind recommending topical tacrolimus as a first-line treatment is that systemic absorption of the drug is trivial. Plus, observational studies of oral tacrolimus in pregnant women who have received a solid organ transplant have shown no increase in congenital malformations.

The task force recommends against the use of topical pimecrolimus (Elidel) or crisaborole (Eucrisa) in pregnancy or lactation due to lack of clinical experience in these settings, Dr. Vestergaard continued.

The task force position is that chlorhexidine and other topical antiseptics – with the notable exception of triclosan – can be used in pregnancy to prevent recurrent skin infections. Aminoglycosides should be avoided, but topical fusidic acid is a reasonable antibiotic for treatment of small areas of clinically infected atopic dermatitis in pregnancy.
 

Systemic therapies

If disease control is insufficient with topical therapy, it’s appropriate to engage in shared decision-making with the patient regarding systemic treatment. She needs to understand up front that the worldwide overall background stillbirth rate in the general population is about 3%, and that severe congenital malformations are present in up to 6% of all live births.

“You need to inform them that they can have systemic therapy and give birth to a child with congenital defects which have nothing to do with the medication,” noted Dr. Vestergaard.

That said, the task force recommends cyclosporine as the off-label, first-line systemic therapy in pregnancy and lactation when long-term treatment is required. This guidance is based largely upon reassuring evidence in solid organ transplant recipients.

The recommended second-line therapy is systemic corticosteroids, but it’s a qualified recommendation. Dr. Vestergaard and colleagues find that systemic corticosteroid therapy is only rarely needed in pregnant AD patients, and the task force recommendation is to limit the use to less than 2-3 weeks and no more than 0.5 mg/kg per day of prednisone. Dexamethasone is not recommended.

Azathioprine should not be started in pregnancy, according to the task force, but when no other options are available, it may be continued in women already on the drug, albeit at half of the prepregnancy dose.

Dupilumab (Dupixent) is to be avoided in pregnant women with AD until more clinical experience becomes available.

Treatment of prospective fathers with AD

The European task force recommends that topical therapies can be prescribed in prospective fathers without any special concerns. The same is true for systemic corticosteroids. Methotrexate should be halted 3 months before planned pregnancy, as is the case for mycophenolate mofetil (CellCept). Azathioprine is recommended when other options have failed. Cyclosporine is deemed a reasonable option in the treatment of men with severe AD at the time of conception if other treatments have failed; of note, neither the Food and Drug Administration nor the European regulatory agency have issued contraindications for the use of the drug in men who wish to become fathers.

Mycophenolate mofetil carries a theoretical risk of teratogenicity. The European task force recommends that men should use condoms while on the drug and for at least 90 days afterward.
 

Unplanned pregnancy in women on systemic therapy

The recommended course of action is to immediately stop systemic therapy, intensify appropriate topical therapy in anticipation of worsening AD, and refer the patient to an obstetrician and a teratology information center for an individualized risk assessment. Methotrexate and mycophenolate mofetil are known teratogens.

The full 16-page task force position paper was published shortly before EADV 2019 (J Eur Acad Dermatol Venereol. 2019 Sep;33[9]:1644-59).

The report was developed without commercial sponsorship. Dr. Vestergaard indicated he has received research grants from and/or serves as a consultant to eight pharmaceutical companies.

[email protected]

MADRID – European atopic dermatitis experts have issued formal guidance on a seriously neglected topic: treatment of the disease during pregnancy, breastfeeding, and in men planning to father children.

Bruce Jancin/MDedge News

The impetus for the project was clear: “Treatment of atopic dermatitis in pregnancy is often forgotten or even ignored,” Christian Vestergaard, MD, PhD, declared at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of the task force’s position paper on the topic, for which he served as first author. The group’s recommendations are based on expert opinion, since randomized clinical trial literature in this area is nonexistent because of ethical concerns. But the task force, comprising a who’s who in European dermatology, drew on a wealth of collective clinical experience in this area.

“We have all of Europe involved in doing this position statement. It’s meant as what we think is proper treatment and what we can say about the different drugs,” explained Dr. Vestergaard, a dermatologist at the University of Aarhus (Denmark).

Most nonobstetricians are intimidated by atopic dermatitis (AD) in pregnancy, and are concerned about the potential for treatment-related harm to the fetus. As a consequence, they are reluctant to recommend anything beyond weak class I topical corticosteroids and emollients. That’s clearly insufficient in light of the vast scope of need, he asserted. After all, AD affects 15%-20% of all children and persists or reappears in adulthood in one out of five of them. Half of those adults are women, many of whom will at some point wish to become pregnant. And many men with AD will eventually want to father children.

A key message from the task force is that untreated AD in pregnancy potentially places the mother and fetus at risk of serious complications, including Staphylococcus aureus infection and eczema herpeticum.

“If you take one thing away from our position paper, it’s that you can use class II or III topical corticosteroids in pregnant women as first-line therapy,” Dr. Vestergaard said.

This stance contradicts a longstanding widely held concern that topical steroids in pregnancy might increase the risk of facial cleft in the offspring, a worry that has been convincingly debunked in a Cochrane systematic review of 14 studies including more than 1.6 million pregnancies. The report concluded there was no association between topical corticosteroids of any potency with preterm delivery, birth defects, or low Apgar scores (Cochrane Database Syst Rev. 2015 Oct 26. doi: 10.1002/14651858.CD007346.pub3).

The task force recommends that if class II or III topical corticosteroid use in pregnancy exceeds 200 g/month, it’s worth considering add-on UV therapy, with narrow band UVB-311 nm as the regimen of choice; it can be used liberally. UV therapy with psoralens is not advised because of a theoretical risk of mutagenicity.

Product labeling for the topical calcineurin inhibitors declares that the agents should not be used during pregnancy. However, the European task force position paper takes issue with that and declares that topical tacrolimus (Protopic) can be considered an off-label first-line therapy in pregnant women with an insufficient response to liberal use of emollients. The same holds true for breastfeeding patients with AD. Just as when topical corticosteroids are used in the nipple area, topical tacrolimus should be applied after nursing, and the nipple area should be gently cleaned before nursing.

The rationale behind recommending topical tacrolimus as a first-line treatment is that systemic absorption of the drug is trivial. Plus, observational studies of oral tacrolimus in pregnant women who have received a solid organ transplant have shown no increase in congenital malformations.

The task force recommends against the use of topical pimecrolimus (Elidel) or crisaborole (Eucrisa) in pregnancy or lactation due to lack of clinical experience in these settings, Dr. Vestergaard continued.

The task force position is that chlorhexidine and other topical antiseptics – with the notable exception of triclosan – can be used in pregnancy to prevent recurrent skin infections. Aminoglycosides should be avoided, but topical fusidic acid is a reasonable antibiotic for treatment of small areas of clinically infected atopic dermatitis in pregnancy.
 

Systemic therapies

If disease control is insufficient with topical therapy, it’s appropriate to engage in shared decision-making with the patient regarding systemic treatment. She needs to understand up front that the worldwide overall background stillbirth rate in the general population is about 3%, and that severe congenital malformations are present in up to 6% of all live births.

“You need to inform them that they can have systemic therapy and give birth to a child with congenital defects which have nothing to do with the medication,” noted Dr. Vestergaard.

That said, the task force recommends cyclosporine as the off-label, first-line systemic therapy in pregnancy and lactation when long-term treatment is required. This guidance is based largely upon reassuring evidence in solid organ transplant recipients.

The recommended second-line therapy is systemic corticosteroids, but it’s a qualified recommendation. Dr. Vestergaard and colleagues find that systemic corticosteroid therapy is only rarely needed in pregnant AD patients, and the task force recommendation is to limit the use to less than 2-3 weeks and no more than 0.5 mg/kg per day of prednisone. Dexamethasone is not recommended.

Azathioprine should not be started in pregnancy, according to the task force, but when no other options are available, it may be continued in women already on the drug, albeit at half of the prepregnancy dose.

Dupilumab (Dupixent) is to be avoided in pregnant women with AD until more clinical experience becomes available.

Treatment of prospective fathers with AD

The European task force recommends that topical therapies can be prescribed in prospective fathers without any special concerns. The same is true for systemic corticosteroids. Methotrexate should be halted 3 months before planned pregnancy, as is the case for mycophenolate mofetil (CellCept). Azathioprine is recommended when other options have failed. Cyclosporine is deemed a reasonable option in the treatment of men with severe AD at the time of conception if other treatments have failed; of note, neither the Food and Drug Administration nor the European regulatory agency have issued contraindications for the use of the drug in men who wish to become fathers.

Mycophenolate mofetil carries a theoretical risk of teratogenicity. The European task force recommends that men should use condoms while on the drug and for at least 90 days afterward.
 

Unplanned pregnancy in women on systemic therapy

The recommended course of action is to immediately stop systemic therapy, intensify appropriate topical therapy in anticipation of worsening AD, and refer the patient to an obstetrician and a teratology information center for an individualized risk assessment. Methotrexate and mycophenolate mofetil are known teratogens.

The full 16-page task force position paper was published shortly before EADV 2019 (J Eur Acad Dermatol Venereol. 2019 Sep;33[9]:1644-59).

The report was developed without commercial sponsorship. Dr. Vestergaard indicated he has received research grants from and/or serves as a consultant to eight pharmaceutical companies.

[email protected]

MADRID – European atopic dermatitis experts have issued formal guidance on a seriously neglected topic: treatment of the disease during pregnancy, breastfeeding, and in men planning to father children.

Bruce Jancin/MDedge News

The impetus for the project was clear: “Treatment of atopic dermatitis in pregnancy is often forgotten or even ignored,” Christian Vestergaard, MD, PhD, declared at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of the task force’s position paper on the topic, for which he served as first author. The group’s recommendations are based on expert opinion, since randomized clinical trial literature in this area is nonexistent because of ethical concerns. But the task force, comprising a who’s who in European dermatology, drew on a wealth of collective clinical experience in this area.

“We have all of Europe involved in doing this position statement. It’s meant as what we think is proper treatment and what we can say about the different drugs,” explained Dr. Vestergaard, a dermatologist at the University of Aarhus (Denmark).

Most nonobstetricians are intimidated by atopic dermatitis (AD) in pregnancy, and are concerned about the potential for treatment-related harm to the fetus. As a consequence, they are reluctant to recommend anything beyond weak class I topical corticosteroids and emollients. That’s clearly insufficient in light of the vast scope of need, he asserted. After all, AD affects 15%-20% of all children and persists or reappears in adulthood in one out of five of them. Half of those adults are women, many of whom will at some point wish to become pregnant. And many men with AD will eventually want to father children.

A key message from the task force is that untreated AD in pregnancy potentially places the mother and fetus at risk of serious complications, including Staphylococcus aureus infection and eczema herpeticum.

“If you take one thing away from our position paper, it’s that you can use class II or III topical corticosteroids in pregnant women as first-line therapy,” Dr. Vestergaard said.

This stance contradicts a longstanding widely held concern that topical steroids in pregnancy might increase the risk of facial cleft in the offspring, a worry that has been convincingly debunked in a Cochrane systematic review of 14 studies including more than 1.6 million pregnancies. The report concluded there was no association between topical corticosteroids of any potency with preterm delivery, birth defects, or low Apgar scores (Cochrane Database Syst Rev. 2015 Oct 26. doi: 10.1002/14651858.CD007346.pub3).

The task force recommends that if class II or III topical corticosteroid use in pregnancy exceeds 200 g/month, it’s worth considering add-on UV therapy, with narrow band UVB-311 nm as the regimen of choice; it can be used liberally. UV therapy with psoralens is not advised because of a theoretical risk of mutagenicity.

Product labeling for the topical calcineurin inhibitors declares that the agents should not be used during pregnancy. However, the European task force position paper takes issue with that and declares that topical tacrolimus (Protopic) can be considered an off-label first-line therapy in pregnant women with an insufficient response to liberal use of emollients. The same holds true for breastfeeding patients with AD. Just as when topical corticosteroids are used in the nipple area, topical tacrolimus should be applied after nursing, and the nipple area should be gently cleaned before nursing.

The rationale behind recommending topical tacrolimus as a first-line treatment is that systemic absorption of the drug is trivial. Plus, observational studies of oral tacrolimus in pregnant women who have received a solid organ transplant have shown no increase in congenital malformations.

The task force recommends against the use of topical pimecrolimus (Elidel) or crisaborole (Eucrisa) in pregnancy or lactation due to lack of clinical experience in these settings, Dr. Vestergaard continued.

The task force position is that chlorhexidine and other topical antiseptics – with the notable exception of triclosan – can be used in pregnancy to prevent recurrent skin infections. Aminoglycosides should be avoided, but topical fusidic acid is a reasonable antibiotic for treatment of small areas of clinically infected atopic dermatitis in pregnancy.
 

Systemic therapies

If disease control is insufficient with topical therapy, it’s appropriate to engage in shared decision-making with the patient regarding systemic treatment. She needs to understand up front that the worldwide overall background stillbirth rate in the general population is about 3%, and that severe congenital malformations are present in up to 6% of all live births.

“You need to inform them that they can have systemic therapy and give birth to a child with congenital defects which have nothing to do with the medication,” noted Dr. Vestergaard.

That said, the task force recommends cyclosporine as the off-label, first-line systemic therapy in pregnancy and lactation when long-term treatment is required. This guidance is based largely upon reassuring evidence in solid organ transplant recipients.

The recommended second-line therapy is systemic corticosteroids, but it’s a qualified recommendation. Dr. Vestergaard and colleagues find that systemic corticosteroid therapy is only rarely needed in pregnant AD patients, and the task force recommendation is to limit the use to less than 2-3 weeks and no more than 0.5 mg/kg per day of prednisone. Dexamethasone is not recommended.

Azathioprine should not be started in pregnancy, according to the task force, but when no other options are available, it may be continued in women already on the drug, albeit at half of the prepregnancy dose.

Dupilumab (Dupixent) is to be avoided in pregnant women with AD until more clinical experience becomes available.

Treatment of prospective fathers with AD

The European task force recommends that topical therapies can be prescribed in prospective fathers without any special concerns. The same is true for systemic corticosteroids. Methotrexate should be halted 3 months before planned pregnancy, as is the case for mycophenolate mofetil (CellCept). Azathioprine is recommended when other options have failed. Cyclosporine is deemed a reasonable option in the treatment of men with severe AD at the time of conception if other treatments have failed; of note, neither the Food and Drug Administration nor the European regulatory agency have issued contraindications for the use of the drug in men who wish to become fathers.

Mycophenolate mofetil carries a theoretical risk of teratogenicity. The European task force recommends that men should use condoms while on the drug and for at least 90 days afterward.
 

Unplanned pregnancy in women on systemic therapy

The recommended course of action is to immediately stop systemic therapy, intensify appropriate topical therapy in anticipation of worsening AD, and refer the patient to an obstetrician and a teratology information center for an individualized risk assessment. Methotrexate and mycophenolate mofetil are known teratogens.

The full 16-page task force position paper was published shortly before EADV 2019 (J Eur Acad Dermatol Venereol. 2019 Sep;33[9]:1644-59).

The report was developed without commercial sponsorship. Dr. Vestergaard indicated he has received research grants from and/or serves as a consultant to eight pharmaceutical companies.

[email protected]

Although these lesions were consistent with actinic keratosis, the location on the palms and the patient’s history of growing up on a ranch in northern Mexico (where he said he was exposed to high arsenic levels in the water and soil), suggested that this was a case of arsenical keratosis. A biopsy excluded frank squamous cell carcinoma; further testing was not needed to make the diagnosis.

While both actinic and arsenical keratoses are precancerous growths with delayed presentations of 20 to 30 years, arsenical keratoses do not typically appear in sun-exposed areas. Rather, these lesions appear on a patient’s palms or soles. They also may present as plate-like hyperpigmentation of the palms and soles or corn-like keratotic papules.

Arsenic occurs naturally in soil and groundwater worldwide and acts as a toxin and carcinogen. It accumulates in the skin, hair, nails, and teeth—making these sites markers of chronic disease. Chronic exposure leads to skin and lung cancer. Cancer of other organs also is possible. Peripheral neuropathy and pancytopenia are hallmarks of chronic exposure.

If arsenical keratosis is suspected, testing for arsenic levels in water or in the work environment is recommended. That said, arsenic exposure is often remote (given the time that has elapsed) and hard to prove.

A blood count and renal and liver function tests should be considered to assess for organ damage. In this case, these tests were normal and the patient was treated with cryotherapy and monitored for recurrence with annual skin exams. Oral retinoids, such as acitretin, have had success in suppressing the frequency and severity of episodes of new lesions in small case reports.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.  

Although these lesions were consistent with actinic keratosis, the location on the palms and the patient’s history of growing up on a ranch in northern Mexico (where he said he was exposed to high arsenic levels in the water and soil), suggested that this was a case of arsenical keratosis. A biopsy excluded frank squamous cell carcinoma; further testing was not needed to make the diagnosis.

While both actinic and arsenical keratoses are precancerous growths with delayed presentations of 20 to 30 years, arsenical keratoses do not typically appear in sun-exposed areas. Rather, these lesions appear on a patient’s palms or soles. They also may present as plate-like hyperpigmentation of the palms and soles or corn-like keratotic papules.

Arsenic occurs naturally in soil and groundwater worldwide and acts as a toxin and carcinogen. It accumulates in the skin, hair, nails, and teeth—making these sites markers of chronic disease. Chronic exposure leads to skin and lung cancer. Cancer of other organs also is possible. Peripheral neuropathy and pancytopenia are hallmarks of chronic exposure.

If arsenical keratosis is suspected, testing for arsenic levels in water or in the work environment is recommended. That said, arsenic exposure is often remote (given the time that has elapsed) and hard to prove.

A blood count and renal and liver function tests should be considered to assess for organ damage. In this case, these tests were normal and the patient was treated with cryotherapy and monitored for recurrence with annual skin exams. Oral retinoids, such as acitretin, have had success in suppressing the frequency and severity of episodes of new lesions in small case reports.

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Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.  

Although these lesions were consistent with actinic keratosis, the location on the palms and the patient’s history of growing up on a ranch in northern Mexico (where he said he was exposed to high arsenic levels in the water and soil), suggested that this was a case of arsenical keratosis. A biopsy excluded frank squamous cell carcinoma; further testing was not needed to make the diagnosis.

While both actinic and arsenical keratoses are precancerous growths with delayed presentations of 20 to 30 years, arsenical keratoses do not typically appear in sun-exposed areas. Rather, these lesions appear on a patient’s palms or soles. They also may present as plate-like hyperpigmentation of the palms and soles or corn-like keratotic papules.

Arsenic occurs naturally in soil and groundwater worldwide and acts as a toxin and carcinogen. It accumulates in the skin, hair, nails, and teeth—making these sites markers of chronic disease. Chronic exposure leads to skin and lung cancer. Cancer of other organs also is possible. Peripheral neuropathy and pancytopenia are hallmarks of chronic exposure.

If arsenical keratosis is suspected, testing for arsenic levels in water or in the work environment is recommended. That said, arsenic exposure is often remote (given the time that has elapsed) and hard to prove.

A blood count and renal and liver function tests should be considered to assess for organ damage. In this case, these tests were normal and the patient was treated with cryotherapy and monitored for recurrence with annual skin exams. Oral retinoids, such as acitretin, have had success in suppressing the frequency and severity of episodes of new lesions in small case reports.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.