TBD Meeting (2884-24)

FROM AAD 2024

SAN DIEGO — In separate studies evaluating treatments for severe forms of alopecia, inhibitors of Janus kinases (JAKs) produced clinically meaningful hair regrowth, according to late-breaking data presented at the annual meeting of  the American Academy of Dermatology.

In one study of brepocitinib, the target was cicatricial alopecia (CA), a form of hair loss for which there are no approved therapies. In the other, a subanalysis from phase 3 trials of ritlecitinib for alopecia areata (AA), hair regrowth was shown in the subset of patients who entered the study with alopecia totalis or alopecia universalis (AT/AU).

Reflecting comments from several experts, including one of the late-breaking session moderators, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said that the CA study, which matched clinical response to changes in CA biomarkers, suggested that the results are a potential breakthrough.

“This is the first placebo-controlled study with an oral JAK inhibitor that not only shows that scarring alopecia can be reversible but also gives insights to the mechanism of action and which patients might respond best,” Emma Guttman-Yassky, MD, PhD, said in an interview. Dr. Guttman-Yassky, professor of Dermatology and Immunology, and director of the Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York City, was the study’s senior investigator.

Scarring Alopecia and Brepocitinib

For the study of scarring alopecia, 49 patients with CA were randomized in a 3:1 ratio to brepocitinib, a first-in-class inhibitor that targets both JAK1 and TYK2, or placebo. Because of the small size of the study, the primary endpoint was the change in CA biomarkers. The secondary outcome was clinical response, but because of a correlation between the two, these were mutually reinforcing.

Of the subtypes, nine patients enrolled in the study had frontal fibrosing alopecia (FFA), 16 had lichen planopilaris (LPP) alopecia, and 24 had central centrifugal cicatricial alopecia (CCCA). All of the forms of CA are more common in women overall and women of color specifically, particularly CCCA. For this analysis, the FFA and LPP subtypes were considered similar for assessing response and were combined.

The data included a comparison of response and safety during the 24-week randomization phase, as well as an additional follow-up conducted after another 24 weeks of open-label treatment. During the second phase, all patients on placebo were switched to active treatment.

Overall, there was a reduction in all four of the key scalp inflammatory biomarkers measured among those in the combined FFA/LLP group. In the placebo group, each of these markers — interferon gamma (IFN-gamma), CCLS, CXCL10, and STAT1 — increased over the same time period. In almost all cases, the differences were statistically significant.

In the CCCA subgroup, the same pattern (an increase among those on placebo but a decrease among those on brepocitinib) was observed for CCLS and CXCL10. For IFN-gamma and STAT1, a rise was observed among those on placebo and those on active treatment, although the rise was greater for placebo.

For clinical response, improvement on brepocitinib was observed on disease activity indexes, particularly among those in the FFA/LLP group, according to Marguerite Meariman, MD, a dermatology resident at Mount Sinai, who presented the results. She called the improvement in clinical activity scores at 48 weeks “dramatic.” Moreover, improvement was apparent within 4 weeks of starting therapy.

For CCCA, a more challenging condition to treat, Dr. Meariman said that no further progression might represent an acceptable response for many patients, but there were also cases of hair regrowth in this subset. Although improvement was not generally on the order seen among those with FFA/LLP, she suggested that there is promise even in these more difficult patients.

Further studies are planned, but Dr. Meariman said that it might be important to focus on early treatment regardless of CA subtype. She noted that patients with less than 5 years disease duration typically did better than those with longer durations.

Ritlecitinib for AT/AU

The analysis of patients with AT/AU was based on a subset analysis from the ALLEGRO phase 2b/3 study of ritlecitinib, which targets JAK3 and TEC kinases. The full results of the ALLEGRO trial were published last year in The Lancet. In the new late-breaker analysis, Severity of Alopecia Tool (SALT) scores were evaluated on an observed or last-observation-carried-forward basis. Generally, responses in the subgroup of patients with AT/AU, who had a median SALT score of 80.3 (signifying 80.3% hair loss) at baseline, were only modestly lower than those in the overall trial.

At 24 months, about 50% of patients achieved a SALT score of 20, according to Melissa Piliang, MD, chair of Dermatology at the Cleveland Clinic, Cleveland, Ohio, who presented the data. In this group, as in the non-AT/AU population, responses climbed over time, and these responses have been maintained for as long as patients have remained on therapy.

At the more rigorous threshold of SALT < 10, the proportion of responders was only slightly lower, meaning a substantial proportion of patients with AT/AU “are achieving 90% or more of hair regrowth, so really an excellent response,” Dr. Piliang said.

For the subgroup with AU, specifically, regrowth of eyebrows and eyelashes was also observed in a substantial proportion, according to Dr. Piliang. Attributed to the often-devastating psychological burden of hair loss, patient-reported assessments of these responses global were generally “even better” than those reported by the investigators.

However, Dr. Piliang advised clinicians to treat AA as early as possible. Despite the benefits seen in the AT/AU subgroup, she pointed out that starting treatment before total hair loss is associated with a higher likelihood of complete or nearly complete hair regrowth.

There are no data from the ALLEGRO trial to determine how long hair regrowth persists after discontinuation of ritlecitinib, which has been approved for the treatment of AA, but Dr. Piliang said that patients should be told that lifelong therapy should be expected in the vast majority of individuals, whether or not AA has advanced to AT/AU.

“In my experience with JAK inhibitors, you lose response when you come off these drugs,” she said.

Dr. Meariman reported a financial relationship with AbbVie. Dr. Piliang reported financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble. Dr. Armstrong reported financial relationships with more than 30 pharmaceutical companies, including those that manufacture JAK inhibitors. Dr. Guttman-Yassky reported financial relationships with more than 30 companies, including those that manufacture JAK inhibitors.

A version of this article appeared on Medscape.com.

FROM AAD 2024

SAN DIEGO — In separate studies evaluating treatments for severe forms of alopecia, inhibitors of Janus kinases (JAKs) produced clinically meaningful hair regrowth, according to late-breaking data presented at the annual meeting of  the American Academy of Dermatology.

In one study of brepocitinib, the target was cicatricial alopecia (CA), a form of hair loss for which there are no approved therapies. In the other, a subanalysis from phase 3 trials of ritlecitinib for alopecia areata (AA), hair regrowth was shown in the subset of patients who entered the study with alopecia totalis or alopecia universalis (AT/AU).

Reflecting comments from several experts, including one of the late-breaking session moderators, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said that the CA study, which matched clinical response to changes in CA biomarkers, suggested that the results are a potential breakthrough.

“This is the first placebo-controlled study with an oral JAK inhibitor that not only shows that scarring alopecia can be reversible but also gives insights to the mechanism of action and which patients might respond best,” Emma Guttman-Yassky, MD, PhD, said in an interview. Dr. Guttman-Yassky, professor of Dermatology and Immunology, and director of the Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York City, was the study’s senior investigator.

Scarring Alopecia and Brepocitinib

For the study of scarring alopecia, 49 patients with CA were randomized in a 3:1 ratio to brepocitinib, a first-in-class inhibitor that targets both JAK1 and TYK2, or placebo. Because of the small size of the study, the primary endpoint was the change in CA biomarkers. The secondary outcome was clinical response, but because of a correlation between the two, these were mutually reinforcing.

Of the subtypes, nine patients enrolled in the study had frontal fibrosing alopecia (FFA), 16 had lichen planopilaris (LPP) alopecia, and 24 had central centrifugal cicatricial alopecia (CCCA). All of the forms of CA are more common in women overall and women of color specifically, particularly CCCA. For this analysis, the FFA and LPP subtypes were considered similar for assessing response and were combined.

The data included a comparison of response and safety during the 24-week randomization phase, as well as an additional follow-up conducted after another 24 weeks of open-label treatment. During the second phase, all patients on placebo were switched to active treatment.

Overall, there was a reduction in all four of the key scalp inflammatory biomarkers measured among those in the combined FFA/LLP group. In the placebo group, each of these markers — interferon gamma (IFN-gamma), CCLS, CXCL10, and STAT1 — increased over the same time period. In almost all cases, the differences were statistically significant.

In the CCCA subgroup, the same pattern (an increase among those on placebo but a decrease among those on brepocitinib) was observed for CCLS and CXCL10. For IFN-gamma and STAT1, a rise was observed among those on placebo and those on active treatment, although the rise was greater for placebo.

For clinical response, improvement on brepocitinib was observed on disease activity indexes, particularly among those in the FFA/LLP group, according to Marguerite Meariman, MD, a dermatology resident at Mount Sinai, who presented the results. She called the improvement in clinical activity scores at 48 weeks “dramatic.” Moreover, improvement was apparent within 4 weeks of starting therapy.

For CCCA, a more challenging condition to treat, Dr. Meariman said that no further progression might represent an acceptable response for many patients, but there were also cases of hair regrowth in this subset. Although improvement was not generally on the order seen among those with FFA/LLP, she suggested that there is promise even in these more difficult patients.

Further studies are planned, but Dr. Meariman said that it might be important to focus on early treatment regardless of CA subtype. She noted that patients with less than 5 years disease duration typically did better than those with longer durations.

Ritlecitinib for AT/AU

The analysis of patients with AT/AU was based on a subset analysis from the ALLEGRO phase 2b/3 study of ritlecitinib, which targets JAK3 and TEC kinases. The full results of the ALLEGRO trial were published last year in The Lancet. In the new late-breaker analysis, Severity of Alopecia Tool (SALT) scores were evaluated on an observed or last-observation-carried-forward basis. Generally, responses in the subgroup of patients with AT/AU, who had a median SALT score of 80.3 (signifying 80.3% hair loss) at baseline, were only modestly lower than those in the overall trial.

At 24 months, about 50% of patients achieved a SALT score of 20, according to Melissa Piliang, MD, chair of Dermatology at the Cleveland Clinic, Cleveland, Ohio, who presented the data. In this group, as in the non-AT/AU population, responses climbed over time, and these responses have been maintained for as long as patients have remained on therapy.

At the more rigorous threshold of SALT < 10, the proportion of responders was only slightly lower, meaning a substantial proportion of patients with AT/AU “are achieving 90% or more of hair regrowth, so really an excellent response,” Dr. Piliang said.

For the subgroup with AU, specifically, regrowth of eyebrows and eyelashes was also observed in a substantial proportion, according to Dr. Piliang. Attributed to the often-devastating psychological burden of hair loss, patient-reported assessments of these responses global were generally “even better” than those reported by the investigators.

However, Dr. Piliang advised clinicians to treat AA as early as possible. Despite the benefits seen in the AT/AU subgroup, she pointed out that starting treatment before total hair loss is associated with a higher likelihood of complete or nearly complete hair regrowth.

There are no data from the ALLEGRO trial to determine how long hair regrowth persists after discontinuation of ritlecitinib, which has been approved for the treatment of AA, but Dr. Piliang said that patients should be told that lifelong therapy should be expected in the vast majority of individuals, whether or not AA has advanced to AT/AU.

“In my experience with JAK inhibitors, you lose response when you come off these drugs,” she said.

Dr. Meariman reported a financial relationship with AbbVie. Dr. Piliang reported financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble. Dr. Armstrong reported financial relationships with more than 30 pharmaceutical companies, including those that manufacture JAK inhibitors. Dr. Guttman-Yassky reported financial relationships with more than 30 companies, including those that manufacture JAK inhibitors.

A version of this article appeared on Medscape.com.

FROM AAD 2024

SAN DIEGO — In separate studies evaluating treatments for severe forms of alopecia, inhibitors of Janus kinases (JAKs) produced clinically meaningful hair regrowth, according to late-breaking data presented at the annual meeting of  the American Academy of Dermatology.

In one study of brepocitinib, the target was cicatricial alopecia (CA), a form of hair loss for which there are no approved therapies. In the other, a subanalysis from phase 3 trials of ritlecitinib for alopecia areata (AA), hair regrowth was shown in the subset of patients who entered the study with alopecia totalis or alopecia universalis (AT/AU).

Reflecting comments from several experts, including one of the late-breaking session moderators, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said that the CA study, which matched clinical response to changes in CA biomarkers, suggested that the results are a potential breakthrough.

“This is the first placebo-controlled study with an oral JAK inhibitor that not only shows that scarring alopecia can be reversible but also gives insights to the mechanism of action and which patients might respond best,” Emma Guttman-Yassky, MD, PhD, said in an interview. Dr. Guttman-Yassky, professor of Dermatology and Immunology, and director of the Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York City, was the study’s senior investigator.

Scarring Alopecia and Brepocitinib

For the study of scarring alopecia, 49 patients with CA were randomized in a 3:1 ratio to brepocitinib, a first-in-class inhibitor that targets both JAK1 and TYK2, or placebo. Because of the small size of the study, the primary endpoint was the change in CA biomarkers. The secondary outcome was clinical response, but because of a correlation between the two, these were mutually reinforcing.

Of the subtypes, nine patients enrolled in the study had frontal fibrosing alopecia (FFA), 16 had lichen planopilaris (LPP) alopecia, and 24 had central centrifugal cicatricial alopecia (CCCA). All of the forms of CA are more common in women overall and women of color specifically, particularly CCCA. For this analysis, the FFA and LPP subtypes were considered similar for assessing response and were combined.

The data included a comparison of response and safety during the 24-week randomization phase, as well as an additional follow-up conducted after another 24 weeks of open-label treatment. During the second phase, all patients on placebo were switched to active treatment.

Overall, there was a reduction in all four of the key scalp inflammatory biomarkers measured among those in the combined FFA/LLP group. In the placebo group, each of these markers — interferon gamma (IFN-gamma), CCLS, CXCL10, and STAT1 — increased over the same time period. In almost all cases, the differences were statistically significant.

In the CCCA subgroup, the same pattern (an increase among those on placebo but a decrease among those on brepocitinib) was observed for CCLS and CXCL10. For IFN-gamma and STAT1, a rise was observed among those on placebo and those on active treatment, although the rise was greater for placebo.

For clinical response, improvement on brepocitinib was observed on disease activity indexes, particularly among those in the FFA/LLP group, according to Marguerite Meariman, MD, a dermatology resident at Mount Sinai, who presented the results. She called the improvement in clinical activity scores at 48 weeks “dramatic.” Moreover, improvement was apparent within 4 weeks of starting therapy.

For CCCA, a more challenging condition to treat, Dr. Meariman said that no further progression might represent an acceptable response for many patients, but there were also cases of hair regrowth in this subset. Although improvement was not generally on the order seen among those with FFA/LLP, she suggested that there is promise even in these more difficult patients.

Further studies are planned, but Dr. Meariman said that it might be important to focus on early treatment regardless of CA subtype. She noted that patients with less than 5 years disease duration typically did better than those with longer durations.

Ritlecitinib for AT/AU

The analysis of patients with AT/AU was based on a subset analysis from the ALLEGRO phase 2b/3 study of ritlecitinib, which targets JAK3 and TEC kinases. The full results of the ALLEGRO trial were published last year in The Lancet. In the new late-breaker analysis, Severity of Alopecia Tool (SALT) scores were evaluated on an observed or last-observation-carried-forward basis. Generally, responses in the subgroup of patients with AT/AU, who had a median SALT score of 80.3 (signifying 80.3% hair loss) at baseline, were only modestly lower than those in the overall trial.

At 24 months, about 50% of patients achieved a SALT score of 20, according to Melissa Piliang, MD, chair of Dermatology at the Cleveland Clinic, Cleveland, Ohio, who presented the data. In this group, as in the non-AT/AU population, responses climbed over time, and these responses have been maintained for as long as patients have remained on therapy.

At the more rigorous threshold of SALT < 10, the proportion of responders was only slightly lower, meaning a substantial proportion of patients with AT/AU “are achieving 90% or more of hair regrowth, so really an excellent response,” Dr. Piliang said.

For the subgroup with AU, specifically, regrowth of eyebrows and eyelashes was also observed in a substantial proportion, according to Dr. Piliang. Attributed to the often-devastating psychological burden of hair loss, patient-reported assessments of these responses global were generally “even better” than those reported by the investigators.

However, Dr. Piliang advised clinicians to treat AA as early as possible. Despite the benefits seen in the AT/AU subgroup, she pointed out that starting treatment before total hair loss is associated with a higher likelihood of complete or nearly complete hair regrowth.

There are no data from the ALLEGRO trial to determine how long hair regrowth persists after discontinuation of ritlecitinib, which has been approved for the treatment of AA, but Dr. Piliang said that patients should be told that lifelong therapy should be expected in the vast majority of individuals, whether or not AA has advanced to AT/AU.

“In my experience with JAK inhibitors, you lose response when you come off these drugs,” she said.

Dr. Meariman reported a financial relationship with AbbVie. Dr. Piliang reported financial relationships with Eli Lilly, Pfizer, and Proctor & Gamble. Dr. Armstrong reported financial relationships with more than 30 pharmaceutical companies, including those that manufacture JAK inhibitors. Dr. Guttman-Yassky reported financial relationships with more than 30 companies, including those that manufacture JAK inhibitors.

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Multiple topical and systemic medications are safe for treating pregnant women with bacterial, viral, and fungal infections, a dermatologist told colleagues at the annual meeting of the American Academy of Dermatology. However, several drugs should be avoided or used with caution because of potential risks during pregnancy. 

When treating bacterial infections in pregnant women, there are many options, “especially for the sort of short-term antibiotic use that we tend to use for treating infections,” said Jenny Murase, MD, of the Palo Alto Foundation Medical Group and the University of California San Francisco.

During a presentation on treating infections in pregnant patients, she made the following recommendations for treating pyogenic infections: 

• Impetigo: First-line treatments are topical mupirocin, oral first-generation cephalosporins, and oral dicloxacillin.
• Cellulitis: Recommended treatments are oral or intravenous penicillin, oral first-generation cephalosporins, and oral dicloxacillin.
• Methicillin-resistant Staphylococcus aureus (MRSA): “Clindamycin is first-line, dependent on bacteria culture and sensitivities,” and because of its safety, “it’s a really good choice for a pregnant woman.” Dr. Murase said. However, be aware of potential inducible resistance and test for the erm gene, she said.
• Abscesses: Incision and drainage are recommended. “Whenever we’re managing a patient with a condition during pregnancy, we want to try to use nonmedications when possible,” Dr. Murase said. “No antibiotic is necessary unless the abscess is greater than 5 cm or if it’s greater than 2 cm with erythema around the abscess.”
• Tuberculosis: The best strategy is rifampin, but peripartum vitamin K prophylaxis for mother and fetus should be used, she said. 

General Infections

With regard to antibiotics to treat general infections — for instance, if a patient with atopic dermatitis has a secondary skin infection — Dr. Murase recommended first-line oral antibiotic therapy with penicillin, first-generation cephalosporins, or dicloxacillin. For second-line therapy, erythromycin is the preferred macrolide over azithromycin and clarithromycin, she said. 

She noted that there is an increased risk for atrial/ventricular septal defects and pyloric stenosis associated with the use of erythromycin when used during the first trimester of pregnancy. In addition, erythromycin estolate increases the risk of liver toxicity, while erythromycin base and erythromycin ethylsuccinate do not. 

Sulfonamides are a second-line line choice up until the third trimester. If given to a patient in the first trimester, she said, “make sure that they are supplementing with folic acid efficiently, at least 0.5 mg a day.” During the peripartum period they are contraindicated, as they pose a risk for hemolytic anemia, hyperbilirubinemia, and kernicterus.

The combination drug trimethoprim/sulfamethoxazole is a second-line choice for complicated infections because of the associated risk for low birth weight and prematurity, Dr. Murase said.

Quinolones are also a second-line option during pregnancy she said, and ciprofloxacin and norfloxacin have been studied the most. “If you have to choose a quinolone for a complicated infection in pregnancy, those would be the quinolones of choice,” Dr. Murase said.

Considering the bad reputation of tetracyclines in pregnancy, dermatologists may be surprised to learn that they are considered a second-line therapy up to 14 weeks’ gestation, she said. After that time, however, they’re contraindicated because of bone growth inhibition, teeth discoloration, and maternal hepatitis.


 

Fungal Infections

As for fungal infections, clotrimazole is the first choice for topical treatment of tinea corporis, followed by miconazole and then ketoconazole, according to Dr. Murase. There are limited data for topical terbinafine, naftifine, and ciclopirox during pregnancy she noted, but they are likely safe.

There is also limited data about these drugs when used for topical treatment of candidiasis during pregnancy. Nystatin is safe, but less effective than other options, Dr. Murase said. Other options include clotrimazole, miconazole, and ketoconazole, which, in animals exposed to high doses, have not been associated with defects, and topical gentian violet (0.5%-1% solution), she noted.

For topical treatment of tinea versicolor during pregnancy, limited application of clotrimazole or miconazole is considered safe, and zinc pyrithione soap or topical benzoyl peroxide soap can be used for more widespread areas. 

Dr. Murase recommended caution when using selenium sulfide since poisoning has been linked to miscarriages, she said. Limited application appears to be safe, “so make sure that the patient is using it on smaller body surface areas.”

As for systemic antifungal treatments, fluconazole, ketoconazole, and itraconazole should be avoided in pregnancy because of the risks of craniosynostosis, congenital heart defects, and skeletal anomalies, Dr. Murase said. However, she referred to a study that found no increased risk of congenital malformations with fluconazole during the first trimester, and a patient could be reassured if, for example, she was treated for a yeast infection before she knew she was pregnant, she said.

Griseofulvin is not recommended during pregnancy, but a 2020 study suggests that terbinafine is safe, she said. In that study, oral or topical terbinafine did not appear to be associated with an increased risk for spontaneous abortion or major malformations. “Certainly, we can wait until after the pregnancy to treat onychomycosis. But I have had situations that even in spite of regular topical therapy, pregnant patients needed to take some kind of oral agent” because of severe itching. 

Viral Infections

For herpes simplex, acyclovir is the top choice, and famciclovir and valacyclovir (Valtrex) are likely safe, but daily prophylaxis is not recommended during pregnancy, Dr. Murase said. 

Because of a lack of data, podofilox, cantharidin, and imiquimod for treating human papillomavirus (HPV) should be avoided, she said. Podophyllin is extremely dangerous in pregnancy and has been linked to maternal and fetal deaths, and malformations, and is contraindicated in pregnancy, she added.

Instead, liquid nitrogen is the treatment of choice for HPV in pregnant patients, she said. 

Trichloracetic acid is the treatment of choice for condylomata acuminata, and squaric acid or intralesional Candida antigen injection for periungual verrucas can be used, she said, and limited applications of salicylic acid are considered safe. 

Dr. Murase highlighted a 2014 paper that she coauthored on the safety of dermatologic medications during pregnancy, noting that an updated report will be published later this year.

Dr. Murase disclosed relationships with Regeneron and UCB (speaker), Sanofi/Regeneron and Bristol-Myers Squibb (advisory board), and UCB, AbbVie, and UpToDate (consulting). 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Multiple topical and systemic medications are safe for treating pregnant women with bacterial, viral, and fungal infections, a dermatologist told colleagues at the annual meeting of the American Academy of Dermatology. However, several drugs should be avoided or used with caution because of potential risks during pregnancy. 

When treating bacterial infections in pregnant women, there are many options, “especially for the sort of short-term antibiotic use that we tend to use for treating infections,” said Jenny Murase, MD, of the Palo Alto Foundation Medical Group and the University of California San Francisco.

During a presentation on treating infections in pregnant patients, she made the following recommendations for treating pyogenic infections: 

• Impetigo: First-line treatments are topical mupirocin, oral first-generation cephalosporins, and oral dicloxacillin.
• Cellulitis: Recommended treatments are oral or intravenous penicillin, oral first-generation cephalosporins, and oral dicloxacillin.
• Methicillin-resistant Staphylococcus aureus (MRSA): “Clindamycin is first-line, dependent on bacteria culture and sensitivities,” and because of its safety, “it’s a really good choice for a pregnant woman.” Dr. Murase said. However, be aware of potential inducible resistance and test for the erm gene, she said.
• Abscesses: Incision and drainage are recommended. “Whenever we’re managing a patient with a condition during pregnancy, we want to try to use nonmedications when possible,” Dr. Murase said. “No antibiotic is necessary unless the abscess is greater than 5 cm or if it’s greater than 2 cm with erythema around the abscess.”
• Tuberculosis: The best strategy is rifampin, but peripartum vitamin K prophylaxis for mother and fetus should be used, she said. 

General Infections

With regard to antibiotics to treat general infections — for instance, if a patient with atopic dermatitis has a secondary skin infection — Dr. Murase recommended first-line oral antibiotic therapy with penicillin, first-generation cephalosporins, or dicloxacillin. For second-line therapy, erythromycin is the preferred macrolide over azithromycin and clarithromycin, she said. 

She noted that there is an increased risk for atrial/ventricular septal defects and pyloric stenosis associated with the use of erythromycin when used during the first trimester of pregnancy. In addition, erythromycin estolate increases the risk of liver toxicity, while erythromycin base and erythromycin ethylsuccinate do not. 

Sulfonamides are a second-line line choice up until the third trimester. If given to a patient in the first trimester, she said, “make sure that they are supplementing with folic acid efficiently, at least 0.5 mg a day.” During the peripartum period they are contraindicated, as they pose a risk for hemolytic anemia, hyperbilirubinemia, and kernicterus.

The combination drug trimethoprim/sulfamethoxazole is a second-line choice for complicated infections because of the associated risk for low birth weight and prematurity, Dr. Murase said.

Quinolones are also a second-line option during pregnancy she said, and ciprofloxacin and norfloxacin have been studied the most. “If you have to choose a quinolone for a complicated infection in pregnancy, those would be the quinolones of choice,” Dr. Murase said.

Considering the bad reputation of tetracyclines in pregnancy, dermatologists may be surprised to learn that they are considered a second-line therapy up to 14 weeks’ gestation, she said. After that time, however, they’re contraindicated because of bone growth inhibition, teeth discoloration, and maternal hepatitis.


 

Fungal Infections

As for fungal infections, clotrimazole is the first choice for topical treatment of tinea corporis, followed by miconazole and then ketoconazole, according to Dr. Murase. There are limited data for topical terbinafine, naftifine, and ciclopirox during pregnancy she noted, but they are likely safe.

There is also limited data about these drugs when used for topical treatment of candidiasis during pregnancy. Nystatin is safe, but less effective than other options, Dr. Murase said. Other options include clotrimazole, miconazole, and ketoconazole, which, in animals exposed to high doses, have not been associated with defects, and topical gentian violet (0.5%-1% solution), she noted.

For topical treatment of tinea versicolor during pregnancy, limited application of clotrimazole or miconazole is considered safe, and zinc pyrithione soap or topical benzoyl peroxide soap can be used for more widespread areas. 

Dr. Murase recommended caution when using selenium sulfide since poisoning has been linked to miscarriages, she said. Limited application appears to be safe, “so make sure that the patient is using it on smaller body surface areas.”

As for systemic antifungal treatments, fluconazole, ketoconazole, and itraconazole should be avoided in pregnancy because of the risks of craniosynostosis, congenital heart defects, and skeletal anomalies, Dr. Murase said. However, she referred to a study that found no increased risk of congenital malformations with fluconazole during the first trimester, and a patient could be reassured if, for example, she was treated for a yeast infection before she knew she was pregnant, she said.

Griseofulvin is not recommended during pregnancy, but a 2020 study suggests that terbinafine is safe, she said. In that study, oral or topical terbinafine did not appear to be associated with an increased risk for spontaneous abortion or major malformations. “Certainly, we can wait until after the pregnancy to treat onychomycosis. But I have had situations that even in spite of regular topical therapy, pregnant patients needed to take some kind of oral agent” because of severe itching. 

Viral Infections

For herpes simplex, acyclovir is the top choice, and famciclovir and valacyclovir (Valtrex) are likely safe, but daily prophylaxis is not recommended during pregnancy, Dr. Murase said. 

Because of a lack of data, podofilox, cantharidin, and imiquimod for treating human papillomavirus (HPV) should be avoided, she said. Podophyllin is extremely dangerous in pregnancy and has been linked to maternal and fetal deaths, and malformations, and is contraindicated in pregnancy, she added.

Instead, liquid nitrogen is the treatment of choice for HPV in pregnant patients, she said. 

Trichloracetic acid is the treatment of choice for condylomata acuminata, and squaric acid or intralesional Candida antigen injection for periungual verrucas can be used, she said, and limited applications of salicylic acid are considered safe. 

Dr. Murase highlighted a 2014 paper that she coauthored on the safety of dermatologic medications during pregnancy, noting that an updated report will be published later this year.

Dr. Murase disclosed relationships with Regeneron and UCB (speaker), Sanofi/Regeneron and Bristol-Myers Squibb (advisory board), and UCB, AbbVie, and UpToDate (consulting). 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Multiple topical and systemic medications are safe for treating pregnant women with bacterial, viral, and fungal infections, a dermatologist told colleagues at the annual meeting of the American Academy of Dermatology. However, several drugs should be avoided or used with caution because of potential risks during pregnancy. 

When treating bacterial infections in pregnant women, there are many options, “especially for the sort of short-term antibiotic use that we tend to use for treating infections,” said Jenny Murase, MD, of the Palo Alto Foundation Medical Group and the University of California San Francisco.

During a presentation on treating infections in pregnant patients, she made the following recommendations for treating pyogenic infections: 

• Impetigo: First-line treatments are topical mupirocin, oral first-generation cephalosporins, and oral dicloxacillin.
• Cellulitis: Recommended treatments are oral or intravenous penicillin, oral first-generation cephalosporins, and oral dicloxacillin.
• Methicillin-resistant Staphylococcus aureus (MRSA): “Clindamycin is first-line, dependent on bacteria culture and sensitivities,” and because of its safety, “it’s a really good choice for a pregnant woman.” Dr. Murase said. However, be aware of potential inducible resistance and test for the erm gene, she said.
• Abscesses: Incision and drainage are recommended. “Whenever we’re managing a patient with a condition during pregnancy, we want to try to use nonmedications when possible,” Dr. Murase said. “No antibiotic is necessary unless the abscess is greater than 5 cm or if it’s greater than 2 cm with erythema around the abscess.”
• Tuberculosis: The best strategy is rifampin, but peripartum vitamin K prophylaxis for mother and fetus should be used, she said. 

General Infections

With regard to antibiotics to treat general infections — for instance, if a patient with atopic dermatitis has a secondary skin infection — Dr. Murase recommended first-line oral antibiotic therapy with penicillin, first-generation cephalosporins, or dicloxacillin. For second-line therapy, erythromycin is the preferred macrolide over azithromycin and clarithromycin, she said. 

She noted that there is an increased risk for atrial/ventricular septal defects and pyloric stenosis associated with the use of erythromycin when used during the first trimester of pregnancy. In addition, erythromycin estolate increases the risk of liver toxicity, while erythromycin base and erythromycin ethylsuccinate do not. 

Sulfonamides are a second-line line choice up until the third trimester. If given to a patient in the first trimester, she said, “make sure that they are supplementing with folic acid efficiently, at least 0.5 mg a day.” During the peripartum period they are contraindicated, as they pose a risk for hemolytic anemia, hyperbilirubinemia, and kernicterus.

The combination drug trimethoprim/sulfamethoxazole is a second-line choice for complicated infections because of the associated risk for low birth weight and prematurity, Dr. Murase said.

Quinolones are also a second-line option during pregnancy she said, and ciprofloxacin and norfloxacin have been studied the most. “If you have to choose a quinolone for a complicated infection in pregnancy, those would be the quinolones of choice,” Dr. Murase said.

Considering the bad reputation of tetracyclines in pregnancy, dermatologists may be surprised to learn that they are considered a second-line therapy up to 14 weeks’ gestation, she said. After that time, however, they’re contraindicated because of bone growth inhibition, teeth discoloration, and maternal hepatitis.


 

Fungal Infections

As for fungal infections, clotrimazole is the first choice for topical treatment of tinea corporis, followed by miconazole and then ketoconazole, according to Dr. Murase. There are limited data for topical terbinafine, naftifine, and ciclopirox during pregnancy she noted, but they are likely safe.

There is also limited data about these drugs when used for topical treatment of candidiasis during pregnancy. Nystatin is safe, but less effective than other options, Dr. Murase said. Other options include clotrimazole, miconazole, and ketoconazole, which, in animals exposed to high doses, have not been associated with defects, and topical gentian violet (0.5%-1% solution), she noted.

For topical treatment of tinea versicolor during pregnancy, limited application of clotrimazole or miconazole is considered safe, and zinc pyrithione soap or topical benzoyl peroxide soap can be used for more widespread areas. 

Dr. Murase recommended caution when using selenium sulfide since poisoning has been linked to miscarriages, she said. Limited application appears to be safe, “so make sure that the patient is using it on smaller body surface areas.”

As for systemic antifungal treatments, fluconazole, ketoconazole, and itraconazole should be avoided in pregnancy because of the risks of craniosynostosis, congenital heart defects, and skeletal anomalies, Dr. Murase said. However, she referred to a study that found no increased risk of congenital malformations with fluconazole during the first trimester, and a patient could be reassured if, for example, she was treated for a yeast infection before she knew she was pregnant, she said.

Griseofulvin is not recommended during pregnancy, but a 2020 study suggests that terbinafine is safe, she said. In that study, oral or topical terbinafine did not appear to be associated with an increased risk for spontaneous abortion or major malformations. “Certainly, we can wait until after the pregnancy to treat onychomycosis. But I have had situations that even in spite of regular topical therapy, pregnant patients needed to take some kind of oral agent” because of severe itching. 

Viral Infections

For herpes simplex, acyclovir is the top choice, and famciclovir and valacyclovir (Valtrex) are likely safe, but daily prophylaxis is not recommended during pregnancy, Dr. Murase said. 

Because of a lack of data, podofilox, cantharidin, and imiquimod for treating human papillomavirus (HPV) should be avoided, she said. Podophyllin is extremely dangerous in pregnancy and has been linked to maternal and fetal deaths, and malformations, and is contraindicated in pregnancy, she added.

Instead, liquid nitrogen is the treatment of choice for HPV in pregnant patients, she said. 

Trichloracetic acid is the treatment of choice for condylomata acuminata, and squaric acid or intralesional Candida antigen injection for periungual verrucas can be used, she said, and limited applications of salicylic acid are considered safe. 

Dr. Murase highlighted a 2014 paper that she coauthored on the safety of dermatologic medications during pregnancy, noting that an updated report will be published later this year.

Dr. Murase disclosed relationships with Regeneron and UCB (speaker), Sanofi/Regeneron and Bristol-Myers Squibb (advisory board), and UCB, AbbVie, and UpToDate (consulting). 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — New guidelines for cutaneous melanoma have been issued by the National Comprehensive Cancer Network (NCCN), creating some new standards of practice that extend a slow divergence from the last set of detailed recommendations released by the American Academy of Dermatology (AAD) in 2019.

Based on the constantly evolving science that drives guidelines, the new set of NCCN recommendations reflects the latest iteration of a consensus effort to define best practice, according to Susan M. Swetter, MD, professor of dermatology and director of the Pigmented Lesion and Melanoma Program at Stanford University in California.

Dr. Swetter chaired the committee that developed the most recent NCCN guidelines, released February 12. She also chaired the work group that developed the AAD recommendations, released in 2019. Differences between the two primarily reflect evolving evidence and expert opinion over time. 
 

Next AAD Guidelines More Than 1 Year Away

The AAD guidelines are developed infrequently and in a process that can take years. The next AAD cutaneous melanoma guidelines are not likely to be released until the end of 2025 or in 2026, Dr. Swetter said at the annual meeting of the American Academy of Dermatology on March 8. In contrast, the NCCN guidelines for cutaneous melanoma are revisited frequently. The last iteration was published only 1 year ago. 

Ted Bosworth/MDedge News

More Than 50% Consensus Generally Required

The NCCN committee that issues periodic guidelines on cutaneous melanoma is formed by a rotating group of interdisciplinary melanoma specialists. More than 30 academic institutions nationwide are generally represented, and the group includes patient advocates. Typically, no comment or recommendation is provided if the committee cannot generate at least a majority endorsement (≥ 50%) on a given topic.

Overall, the majority of guidelines, including those issued by the NCCN and the AAD, are aligned, except to the degree of the time lag that provides different sets of evidence to consider. The rationale for keeping abreast of the NCCN recommendations is that updates are more frequent, according to Dr. Swetter, who noted that these are available for free once a user has registered on the NCCN website. 

Importantly, guidelines not only identify what further steps can be taken to improve diagnostic accuracy or outcomes but what practices can be abandoned to improve the benefit-to-risk ratio. As an example, surgical margins for primary melanomas have been becoming progressively smaller on the basis of evidence that larger margins increase morbidity without improving outcomes.

Although Dr. Swetter acknowledged that “we still haven’t identified the narrowest, most efficacious margins for cutaneous melanoma,” she cited studies now suggesting that margins of 2 cm appear to be sufficient even for advanced T3 and T4 tumors. Prior to the 1970s, margins of 5 cm or greater were common.

There are still many unanswered questions about optimal margins, but the 2023 NCCN guidelines already called for surgical margins of at least 1 cm and no more than 2 cm for large invasive melanomas when clinically measured around the primary tumor. Dr. Swetter said that even smaller margins can be considered “to accommodate function and/or the anatomic location.”
 

Best Margins for MIS Undefined

So far, there are no randomized trials yet to guide surgical margins or depth for many melanoma subtypes, including melanoma in situ (MIS). These are the types of data, when they become available, that change guidelines.

The list of procedures often performed, but for which there is no specific guidance from NCCN or other organizations, is long. Numerous examples were provided during the AAD symposium on guidelines, during which Dr. Swetter spoke. The bedside diagnosis of cutaneous melanoma with noninvasive testing was one.

Describing the 2-gene molecular assay for the evaluation of a suspected melanoma, Caroline C. Kim, MD, director of the Melanoma and Pigmented Lesion Program at Tufts University in Boston, explained that this tool, which is based on the presence of the LINC00158 gene and the preferentially expressed antigen in melanoma (PRAME), has limited utility as a tool for establishing a diagnosis of melanoma. But, she said, it has reasonably good reliability for ruling out melanoma, thereby providing a basis to avoid or delay further diagnostic steps, such as biopsy.

Skin biopsy, as established in the guidelines, “is still the gold standard,” but there are numerous studies indicating that patients negative for both LINC00158 and PRAME have a low risk for melanoma, she said.

“A double negative result is not 100% effective, but it is high,” said Dr. Kim, who provided several examples whereby she employed the test to follow the patient rather than do invasive testing.

This test is gaining popularity, according to Dr. Kim, who cited several surveys suggesting growing use among clinicians, but she characterized it as an adjunctive approach that should be considered in the context of guidelines. It is an example of an approach that is not yet standard practice but can be helpful if used appropriately, she noted.

Dr. Swetter and Dr. Kim report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

SAN DIEGO — New guidelines for cutaneous melanoma have been issued by the National Comprehensive Cancer Network (NCCN), creating some new standards of practice that extend a slow divergence from the last set of detailed recommendations released by the American Academy of Dermatology (AAD) in 2019.

Based on the constantly evolving science that drives guidelines, the new set of NCCN recommendations reflects the latest iteration of a consensus effort to define best practice, according to Susan M. Swetter, MD, professor of dermatology and director of the Pigmented Lesion and Melanoma Program at Stanford University in California.

Dr. Swetter chaired the committee that developed the most recent NCCN guidelines, released February 12. She also chaired the work group that developed the AAD recommendations, released in 2019. Differences between the two primarily reflect evolving evidence and expert opinion over time. 
 

Next AAD Guidelines More Than 1 Year Away

The AAD guidelines are developed infrequently and in a process that can take years. The next AAD cutaneous melanoma guidelines are not likely to be released until the end of 2025 or in 2026, Dr. Swetter said at the annual meeting of the American Academy of Dermatology on March 8. In contrast, the NCCN guidelines for cutaneous melanoma are revisited frequently. The last iteration was published only 1 year ago. 

Ted Bosworth/MDedge News

More Than 50% Consensus Generally Required

The NCCN committee that issues periodic guidelines on cutaneous melanoma is formed by a rotating group of interdisciplinary melanoma specialists. More than 30 academic institutions nationwide are generally represented, and the group includes patient advocates. Typically, no comment or recommendation is provided if the committee cannot generate at least a majority endorsement (≥ 50%) on a given topic.

Overall, the majority of guidelines, including those issued by the NCCN and the AAD, are aligned, except to the degree of the time lag that provides different sets of evidence to consider. The rationale for keeping abreast of the NCCN recommendations is that updates are more frequent, according to Dr. Swetter, who noted that these are available for free once a user has registered on the NCCN website. 

Importantly, guidelines not only identify what further steps can be taken to improve diagnostic accuracy or outcomes but what practices can be abandoned to improve the benefit-to-risk ratio. As an example, surgical margins for primary melanomas have been becoming progressively smaller on the basis of evidence that larger margins increase morbidity without improving outcomes.

Although Dr. Swetter acknowledged that “we still haven’t identified the narrowest, most efficacious margins for cutaneous melanoma,” she cited studies now suggesting that margins of 2 cm appear to be sufficient even for advanced T3 and T4 tumors. Prior to the 1970s, margins of 5 cm or greater were common.

There are still many unanswered questions about optimal margins, but the 2023 NCCN guidelines already called for surgical margins of at least 1 cm and no more than 2 cm for large invasive melanomas when clinically measured around the primary tumor. Dr. Swetter said that even smaller margins can be considered “to accommodate function and/or the anatomic location.”
 

Best Margins for MIS Undefined

So far, there are no randomized trials yet to guide surgical margins or depth for many melanoma subtypes, including melanoma in situ (MIS). These are the types of data, when they become available, that change guidelines.

The list of procedures often performed, but for which there is no specific guidance from NCCN or other organizations, is long. Numerous examples were provided during the AAD symposium on guidelines, during which Dr. Swetter spoke. The bedside diagnosis of cutaneous melanoma with noninvasive testing was one.

Describing the 2-gene molecular assay for the evaluation of a suspected melanoma, Caroline C. Kim, MD, director of the Melanoma and Pigmented Lesion Program at Tufts University in Boston, explained that this tool, which is based on the presence of the LINC00158 gene and the preferentially expressed antigen in melanoma (PRAME), has limited utility as a tool for establishing a diagnosis of melanoma. But, she said, it has reasonably good reliability for ruling out melanoma, thereby providing a basis to avoid or delay further diagnostic steps, such as biopsy.

Skin biopsy, as established in the guidelines, “is still the gold standard,” but there are numerous studies indicating that patients negative for both LINC00158 and PRAME have a low risk for melanoma, she said.

“A double negative result is not 100% effective, but it is high,” said Dr. Kim, who provided several examples whereby she employed the test to follow the patient rather than do invasive testing.

This test is gaining popularity, according to Dr. Kim, who cited several surveys suggesting growing use among clinicians, but she characterized it as an adjunctive approach that should be considered in the context of guidelines. It is an example of an approach that is not yet standard practice but can be helpful if used appropriately, she noted.

Dr. Swetter and Dr. Kim report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

SAN DIEGO — New guidelines for cutaneous melanoma have been issued by the National Comprehensive Cancer Network (NCCN), creating some new standards of practice that extend a slow divergence from the last set of detailed recommendations released by the American Academy of Dermatology (AAD) in 2019.

Based on the constantly evolving science that drives guidelines, the new set of NCCN recommendations reflects the latest iteration of a consensus effort to define best practice, according to Susan M. Swetter, MD, professor of dermatology and director of the Pigmented Lesion and Melanoma Program at Stanford University in California.

Dr. Swetter chaired the committee that developed the most recent NCCN guidelines, released February 12. She also chaired the work group that developed the AAD recommendations, released in 2019. Differences between the two primarily reflect evolving evidence and expert opinion over time. 
 

Next AAD Guidelines More Than 1 Year Away

The AAD guidelines are developed infrequently and in a process that can take years. The next AAD cutaneous melanoma guidelines are not likely to be released until the end of 2025 or in 2026, Dr. Swetter said at the annual meeting of the American Academy of Dermatology on March 8. In contrast, the NCCN guidelines for cutaneous melanoma are revisited frequently. The last iteration was published only 1 year ago. 

Ted Bosworth/MDedge News

More Than 50% Consensus Generally Required

The NCCN committee that issues periodic guidelines on cutaneous melanoma is formed by a rotating group of interdisciplinary melanoma specialists. More than 30 academic institutions nationwide are generally represented, and the group includes patient advocates. Typically, no comment or recommendation is provided if the committee cannot generate at least a majority endorsement (≥ 50%) on a given topic.

Overall, the majority of guidelines, including those issued by the NCCN and the AAD, are aligned, except to the degree of the time lag that provides different sets of evidence to consider. The rationale for keeping abreast of the NCCN recommendations is that updates are more frequent, according to Dr. Swetter, who noted that these are available for free once a user has registered on the NCCN website. 

Importantly, guidelines not only identify what further steps can be taken to improve diagnostic accuracy or outcomes but what practices can be abandoned to improve the benefit-to-risk ratio. As an example, surgical margins for primary melanomas have been becoming progressively smaller on the basis of evidence that larger margins increase morbidity without improving outcomes.

Although Dr. Swetter acknowledged that “we still haven’t identified the narrowest, most efficacious margins for cutaneous melanoma,” she cited studies now suggesting that margins of 2 cm appear to be sufficient even for advanced T3 and T4 tumors. Prior to the 1970s, margins of 5 cm or greater were common.

There are still many unanswered questions about optimal margins, but the 2023 NCCN guidelines already called for surgical margins of at least 1 cm and no more than 2 cm for large invasive melanomas when clinically measured around the primary tumor. Dr. Swetter said that even smaller margins can be considered “to accommodate function and/or the anatomic location.”
 

Best Margins for MIS Undefined

So far, there are no randomized trials yet to guide surgical margins or depth for many melanoma subtypes, including melanoma in situ (MIS). These are the types of data, when they become available, that change guidelines.

The list of procedures often performed, but for which there is no specific guidance from NCCN or other organizations, is long. Numerous examples were provided during the AAD symposium on guidelines, during which Dr. Swetter spoke. The bedside diagnosis of cutaneous melanoma with noninvasive testing was one.

Describing the 2-gene molecular assay for the evaluation of a suspected melanoma, Caroline C. Kim, MD, director of the Melanoma and Pigmented Lesion Program at Tufts University in Boston, explained that this tool, which is based on the presence of the LINC00158 gene and the preferentially expressed antigen in melanoma (PRAME), has limited utility as a tool for establishing a diagnosis of melanoma. But, she said, it has reasonably good reliability for ruling out melanoma, thereby providing a basis to avoid or delay further diagnostic steps, such as biopsy.

Skin biopsy, as established in the guidelines, “is still the gold standard,” but there are numerous studies indicating that patients negative for both LINC00158 and PRAME have a low risk for melanoma, she said.

“A double negative result is not 100% effective, but it is high,” said Dr. Kim, who provided several examples whereby she employed the test to follow the patient rather than do invasive testing.

This test is gaining popularity, according to Dr. Kim, who cited several surveys suggesting growing use among clinicians, but she characterized it as an adjunctive approach that should be considered in the context of guidelines. It is an example of an approach that is not yet standard practice but can be helpful if used appropriately, she noted.

Dr. Swetter and Dr. Kim report no relevant financial relationships. 

A version of this article appeared on Medscape.com.