MDedge Dermatology

Key clinical point: A dose of 4 mg baricitinib plus topical corticosteroids (TCS) demonstrated superior efficacy compared to placebo+TCS in pediatric patients with moderate-to-severe atopic dermatitis (AD), with the safety profile being consistent with previous studies involving adults with moderate-to-severe AD.

Major finding: At week 16, a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS achieved a validated Investigator’s Global Assessment for AD score of 0 or 1 with a ≥2-point improvement (41.7% vs 16.4%; P < .0001); no significant difference was observed between the 2 mg/1 mg baricitinib and placebo groups. No new safety signals were reported.

Study details: This multicenter phase 3 study, BREEZE-AD-PEDS, included 483 pediatric patients aged 2 to <18 years with moderate-to-severe AD and inadequate response to TCS or systemic treatments who were randomly assigned to receive 4 mg baricitinib+TCS, 2 mg baricitinib+TCS, 1 mg baricitinib+TCS, or placebo+TCS.

Disclosures: Baricitinib was developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported various ties, including employment and stock ownership, with Eli Lilly or others.

Source: Torrelo A et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate-to-severe atopic dermatitis with inadequate response to topical corticosteroids: Results from a phase 3, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). Br J Dermatol. 2023 (Mar 31). Doi: 10.1093/bjd/ljad096

Key clinical point: A dose of 4 mg baricitinib plus topical corticosteroids (TCS) demonstrated superior efficacy compared to placebo+TCS in pediatric patients with moderate-to-severe atopic dermatitis (AD), with the safety profile being consistent with previous studies involving adults with moderate-to-severe AD.

Major finding: At week 16, a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS achieved a validated Investigator’s Global Assessment for AD score of 0 or 1 with a ≥2-point improvement (41.7% vs 16.4%; P < .0001); no significant difference was observed between the 2 mg/1 mg baricitinib and placebo groups. No new safety signals were reported.

Study details: This multicenter phase 3 study, BREEZE-AD-PEDS, included 483 pediatric patients aged 2 to <18 years with moderate-to-severe AD and inadequate response to TCS or systemic treatments who were randomly assigned to receive 4 mg baricitinib+TCS, 2 mg baricitinib+TCS, 1 mg baricitinib+TCS, or placebo+TCS.

Disclosures: Baricitinib was developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported various ties, including employment and stock ownership, with Eli Lilly or others.

Source: Torrelo A et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate-to-severe atopic dermatitis with inadequate response to topical corticosteroids: Results from a phase 3, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). Br J Dermatol. 2023 (Mar 31). Doi: 10.1093/bjd/ljad096

Key clinical point: A dose of 4 mg baricitinib plus topical corticosteroids (TCS) demonstrated superior efficacy compared to placebo+TCS in pediatric patients with moderate-to-severe atopic dermatitis (AD), with the safety profile being consistent with previous studies involving adults with moderate-to-severe AD.

Major finding: At week 16, a significantly higher proportion of patients receiving 4 mg baricitinib+TCS vs placebo+TCS achieved a validated Investigator’s Global Assessment for AD score of 0 or 1 with a ≥2-point improvement (41.7% vs 16.4%; P < .0001); no significant difference was observed between the 2 mg/1 mg baricitinib and placebo groups. No new safety signals were reported.

Study details: This multicenter phase 3 study, BREEZE-AD-PEDS, included 483 pediatric patients aged 2 to <18 years with moderate-to-severe AD and inadequate response to TCS or systemic treatments who were randomly assigned to receive 4 mg baricitinib+TCS, 2 mg baricitinib+TCS, 1 mg baricitinib+TCS, or placebo+TCS.

Disclosures: Baricitinib was developed by Eli Lilly and Company, under license from Incyte Corporation. Some authors reported various ties, including employment and stock ownership, with Eli Lilly or others.

Source: Torrelo A et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate-to-severe atopic dermatitis with inadequate response to topical corticosteroids: Results from a phase 3, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). Br J Dermatol. 2023 (Mar 31). Doi: 10.1093/bjd/ljad096

Key clinical point: Lebrikizumab significantly improved the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 16, in the ADvocate1 and ADvocate2 trials, a significantly higher proportion of patients receiving lebrikizumab vs placebo achieved an Investigator’s Global Assessment score of 0 or 1 (43.1% vs 12.7% and 33.2% vs 10.8%, respectively) and a ≥75% improvement in the Eczema Area and Severity Index (58.8% vs 16.2% and 52.1% vs 18.1%, respectively; all P < .001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: Findings are from two identical phase 3 studies, ADvocate1 (n = 424) and ADvocate2 (n = 427), including adults (≥18 years) and adolescents (12 to <18 years) with moderate-to-severe AD who were randomly assigned to receive lebrikizumab or placebo over 16-week induction and 36-week maintenance periods.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Some authors reported various ties, including employment, with Eli Lilly or others.

Source: Silverberg JI et al for the ADvocate1 and ADvocate2 Investigators. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080-1091 (Mar 15). Doi: 10.1056/NEJMoa2206714

Key clinical point: Lebrikizumab significantly improved the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 16, in the ADvocate1 and ADvocate2 trials, a significantly higher proportion of patients receiving lebrikizumab vs placebo achieved an Investigator’s Global Assessment score of 0 or 1 (43.1% vs 12.7% and 33.2% vs 10.8%, respectively) and a ≥75% improvement in the Eczema Area and Severity Index (58.8% vs 16.2% and 52.1% vs 18.1%, respectively; all P < .001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: Findings are from two identical phase 3 studies, ADvocate1 (n = 424) and ADvocate2 (n = 427), including adults (≥18 years) and adolescents (12 to <18 years) with moderate-to-severe AD who were randomly assigned to receive lebrikizumab or placebo over 16-week induction and 36-week maintenance periods.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Some authors reported various ties, including employment, with Eli Lilly or others.

Source: Silverberg JI et al for the ADvocate1 and ADvocate2 Investigators. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080-1091 (Mar 15). Doi: 10.1056/NEJMoa2206714

Key clinical point: Lebrikizumab significantly improved the signs and symptoms of moderate-to-severe atopic dermatitis (AD) in adults and adolescents.

Major finding: At week 16, in the ADvocate1 and ADvocate2 trials, a significantly higher proportion of patients receiving lebrikizumab vs placebo achieved an Investigator’s Global Assessment score of 0 or 1 (43.1% vs 12.7% and 33.2% vs 10.8%, respectively) and a ≥75% improvement in the Eczema Area and Severity Index (58.8% vs 16.2% and 52.1% vs 18.1%, respectively; all P < .001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: Findings are from two identical phase 3 studies, ADvocate1 (n = 424) and ADvocate2 (n = 427), including adults (≥18 years) and adolescents (12 to <18 years) with moderate-to-severe AD who were randomly assigned to receive lebrikizumab or placebo over 16-week induction and 36-week maintenance periods.

Disclosures: This study was sponsored by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Some authors reported various ties, including employment, with Eli Lilly or others.

Source: Silverberg JI et al for the ADvocate1 and ADvocate2 Investigators. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080-1091 (Mar 15). Doi: 10.1056/NEJMoa2206714

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Among patients with unresectable desmoplastic melanoma (DM), a prospective trial showed that single-agent treatment with the programmed death 1 (PD-1) inhibitor pembrolizumab led to a dramatic overall response rate.

The findings could represent a new standard of treatment for this extremely rare tumor.

The study was inspired by a previous retrospective analysis which found an overall response rate of 77% and a complete response of 32% to anti–PD-1 monotherapy.

The ORR is about double what is seen in melanoma more generally, according to Kari Kendra, MD, PhD, who presented the study at the annual meeting of the American Association for Cancer Research.

“Our study was a positive study. Of note, in the retrospective study, they saw a complete response rate of 32%, which was amazingly similar to what we found. [The findings support] the use of single agent anti–PD-1 immunotherapy as first line treatment for most patients with unresectable desmoplastic melanoma. [There was 89% overall response and we saw] dramatic responses across the board,” said Dr. Kendra, who is a medical oncologist at Ohio State University Wexner Medical Center, Columbus.

The findings drew a strong reaction. “In a rare tumor session, to see response curves like that, it’s just outstanding,” said the session’s cochair Brian Van Tine, MD, PhD, who is a professor of medical oncology at Washington University in St. Louis.

“This really is one of the highest tumor response rates to immunotherapy that we are seeing in any cancer. And I think may also highlight the fact that we shouldn’t think of all cutaneous melanomas as one disease, given the heterogeneity in tumor responses based on some of the pathologic and molecular characteristics,” said Zeynep Aroglu, MD, who served as a discussant but was also one of the investigators who enrolled patients for the trial.

Desmoplastic melanoma represents about 4% of all cutaneous melanoma diagnoses, and its unique pathology can make it difficult to diagnose. That often leads to a late diagnosis, according to Dr. Aroglu. They typically occur in elderly patients, in the head and neck area, and are associated with sun exposure. DM also tends to have a high mutation burden, Dr. Aroglu said during the session.

It remains to be seen why there is such a high response rate in this tumor type, even among tumor types with mutation burdens that are nearly as high. DM tumors are often driven by neurofibromatosis type 1, but other tumors driven by NF-1 don’t have as high of a response rate to immunotherapy. The tumor environment could also play a role, she said.

“Is it a combination of all these factors? I think some of the ongoing analysis of tumor samples that Dr. Kendra mentioned may help to answer some of these questions,” Dr. Aroglu continued.

She also noted that the melanoma field is increasingly turning to combination of anti–PD-1 therapy with agents like that target LAG3 or CTLA4. Such combinations can achieve higher response rates, but at a cost of higher rates of grade 3-4 adverse events than anti–PD-1 inhibitors alone. “I wonder if for desmoplastic melanomas in light of this data, do we consider de-escalating therapy, given these very high response rates to PD-1 alone, given also the elderly age of many of these patients, because even the PD-1–LAG3 combo still has a higher rate of toxicity than PD-1 monotherapy. Perhaps the immunotherapy combinations can be reserved for those rare desmoplastic patients who are resistant to PD-1 alone,” said Dr. Aroglu.
 

Study details and adverse events

Twenty-seven patients were enrolled in the study; 93% were male, all were White, and 22% had elevated baseline lactate dehydrogenase. About 63% had disease located in the head and neck area, 33% experienced a complete response (P < .001), and 56% had a partial response for an ORR of 89%. The result surpassed the primary endpoint target of at least a 20% complete response rate.

The 2-year progression-free survival was 74%, and 2-year overall survival was 89%. The most common toxicities were fatigue (56%), diarrhea (33%), maculopapular rash (30%), pruritus (22%), anemia (19%), arthralgia (19%), and decreased lymphocyte count (19%). There were two grade 4 adverse events: a lipase increase and a lung infection accompanied by sepsis.

The researchers also carried out whole exome sequencing of biopsies and found that 67% had NF-1 loss of function mutations.

Dr. Aroglu has served on advisory boards for Pfizer, Array, Eisai, Genentech, Natera, Novartis, OncoSec, and Regeneron. She has received research support from Boehringer Ingelheim, Pfizer, and Novartis. Dr. Kendra has received institutional support from Bristol Myers-Squibb and trial support from CheckMate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Merck, Novartis, and Varian Medical Systems. Dr. Van Tine has financial relationships with a wide range of pharmaceutical companies.

Time for my periodic reminder about your Occupational Health and Safety Administration (OSHA) obligations. The health care field still has the most work-related illness and injury reports of any industry in the United States, and OSHA standards are in place to minimize potential workplace incidents.

Now might be a good time to get out your OSHA logs, walk through your office, and confirm that you remain in compliance with all the applicable regulations. Even if you hold regular safety meetings (which all too often is not the case), the occasional comprehensive review is always a good idea, and could save you a bundle in fines.

For starters, do you have an official OSHA poster, enumerating employee rights and explaining how to file complaints? Every office must have one posted in plain sight, and it is the first thing an OSHA inspector will look for. You can download one from OSHA’s website or order one at no charge by calling 800-321-OSHA.

The poster discusses the “general standards” that all workplaces must comply with to avoid work-related illnesses and injuries. The standards most applicable to medical offices are those dealing with personal protective equipment (PPE), bloodborne pathogens, hazard communication, and – increasingly, of late – ionizing radiation.

Physicians have become all too familiar with the PPE standard as a result of the COVID pandemic. Ironically, OSHA considers PPE a less acceptable means of employee protection than the other standards, as safe work practices should always supersede safety equipment. Nevertheless, employers must have a PPE program in place to train employees on what equipment is necessary, and under which conditions.

You also need a written exposure control plan for bloodborne pathogens. It should document your use of such protective equipment as gloves, face and eye protection, needle guards, and gowns, and your implementation of universal precautions – and it is supposed to be updated annually, to reflect changes in technology. You must provide all at-risk employees with hepatitis B vaccine at no cost to them. You also must provide and pay for appropriate medical treatment and follow-up after any exposure to a dangerous pathogen.

You need not adopt every new safety device as it comes on the market, but you should document which ones you are using – and which you pass up – and why. For example, you and your employees may decide not to purchase a new safety needle because you don’t think it will improve safety, or that it will be more trouble than it’s worth; but you should document how you arrived at that decision, and why you feel that your current protocol is as good or better.

The hazard communication (or right-to-know) standard involves compiling a list of hazardous substances, which all employees have a right to know about. Keep in mind that OSHA’s list includes alcohol, hydrogen peroxide, acetone, liquid nitrogen, and other substances that you might not consider particularly dangerous, but are nevertheless classified as “hazardous.” For each substance, your employees must have access to the manufacturer-supplied Material Safety Data Sheet, which outlines the proper procedures for working with a specific material, and for handling and containing it in a spill or other emergency.

If your office has x-ray equipment, or you are considering one of the new image-guided superficial radiotherapy machines, you must be in compliance with the ionizing radiation standard, which entails shielding, radiation monitors, and clear labeling of equipment.

Other, more general regulations include the physical setup of your office. Everyone must be able to evacuate quickly in case of fire or other emergencies. At a minimum, you (or the owner of the office building) are expected to establish exit routes to accommodate all employees and to post easily visible evacuation diagrams.

Examine all electrical devices and their power sources. All electrically powered equipment – medical, clerical, or anything else in the office – must operate safely. Pay particular attention to the way wall outlets are set up. Make sure each outlet has sufficient power to run the equipment plugged into it, and that circuit breakers are present and functioning. And beware the common situation of too many gadgets running off a single circuit.

Other components of the rule include proper containment of regulated medical waste, identification of regulated-waste containers, sharps disposal boxes, and periodic employee training regarding all of these things.

Federal OSHA regulations do not require medical and dental offices to keep an injury and illness log, as other businesses must; but your state may have a requirement that supersedes the federal law. Check with your state, or with your local OSHA office, regarding any such requirements.

It is a mistake to take OSHA regulations lightly; failure to comply with them can result in stiff penalties running into many thousands of dollars. How can you be certain you are complying with all the rules? The easiest and cheapest way is to call your local OSHA office and request an inspection. Why would you do that? Because OSHA issues no citations during voluntary inspections as long as you agree to remedy any violations they find.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Time for my periodic reminder about your Occupational Health and Safety Administration (OSHA) obligations. The health care field still has the most work-related illness and injury reports of any industry in the United States, and OSHA standards are in place to minimize potential workplace incidents.

Now might be a good time to get out your OSHA logs, walk through your office, and confirm that you remain in compliance with all the applicable regulations. Even if you hold regular safety meetings (which all too often is not the case), the occasional comprehensive review is always a good idea, and could save you a bundle in fines.

For starters, do you have an official OSHA poster, enumerating employee rights and explaining how to file complaints? Every office must have one posted in plain sight, and it is the first thing an OSHA inspector will look for. You can download one from OSHA’s website or order one at no charge by calling 800-321-OSHA.

The poster discusses the “general standards” that all workplaces must comply with to avoid work-related illnesses and injuries. The standards most applicable to medical offices are those dealing with personal protective equipment (PPE), bloodborne pathogens, hazard communication, and – increasingly, of late – ionizing radiation.

Physicians have become all too familiar with the PPE standard as a result of the COVID pandemic. Ironically, OSHA considers PPE a less acceptable means of employee protection than the other standards, as safe work practices should always supersede safety equipment. Nevertheless, employers must have a PPE program in place to train employees on what equipment is necessary, and under which conditions.

You also need a written exposure control plan for bloodborne pathogens. It should document your use of such protective equipment as gloves, face and eye protection, needle guards, and gowns, and your implementation of universal precautions – and it is supposed to be updated annually, to reflect changes in technology. You must provide all at-risk employees with hepatitis B vaccine at no cost to them. You also must provide and pay for appropriate medical treatment and follow-up after any exposure to a dangerous pathogen.

You need not adopt every new safety device as it comes on the market, but you should document which ones you are using – and which you pass up – and why. For example, you and your employees may decide not to purchase a new safety needle because you don’t think it will improve safety, or that it will be more trouble than it’s worth; but you should document how you arrived at that decision, and why you feel that your current protocol is as good or better.

The hazard communication (or right-to-know) standard involves compiling a list of hazardous substances, which all employees have a right to know about. Keep in mind that OSHA’s list includes alcohol, hydrogen peroxide, acetone, liquid nitrogen, and other substances that you might not consider particularly dangerous, but are nevertheless classified as “hazardous.” For each substance, your employees must have access to the manufacturer-supplied Material Safety Data Sheet, which outlines the proper procedures for working with a specific material, and for handling and containing it in a spill or other emergency.

If your office has x-ray equipment, or you are considering one of the new image-guided superficial radiotherapy machines, you must be in compliance with the ionizing radiation standard, which entails shielding, radiation monitors, and clear labeling of equipment.

Other, more general regulations include the physical setup of your office. Everyone must be able to evacuate quickly in case of fire or other emergencies. At a minimum, you (or the owner of the office building) are expected to establish exit routes to accommodate all employees and to post easily visible evacuation diagrams.

Examine all electrical devices and their power sources. All electrically powered equipment – medical, clerical, or anything else in the office – must operate safely. Pay particular attention to the way wall outlets are set up. Make sure each outlet has sufficient power to run the equipment plugged into it, and that circuit breakers are present and functioning. And beware the common situation of too many gadgets running off a single circuit.

Other components of the rule include proper containment of regulated medical waste, identification of regulated-waste containers, sharps disposal boxes, and periodic employee training regarding all of these things.

Federal OSHA regulations do not require medical and dental offices to keep an injury and illness log, as other businesses must; but your state may have a requirement that supersedes the federal law. Check with your state, or with your local OSHA office, regarding any such requirements.

It is a mistake to take OSHA regulations lightly; failure to comply with them can result in stiff penalties running into many thousands of dollars. How can you be certain you are complying with all the rules? The easiest and cheapest way is to call your local OSHA office and request an inspection. Why would you do that? Because OSHA issues no citations during voluntary inspections as long as you agree to remedy any violations they find.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Time for my periodic reminder about your Occupational Health and Safety Administration (OSHA) obligations. The health care field still has the most work-related illness and injury reports of any industry in the United States, and OSHA standards are in place to minimize potential workplace incidents.

Now might be a good time to get out your OSHA logs, walk through your office, and confirm that you remain in compliance with all the applicable regulations. Even if you hold regular safety meetings (which all too often is not the case), the occasional comprehensive review is always a good idea, and could save you a bundle in fines.

For starters, do you have an official OSHA poster, enumerating employee rights and explaining how to file complaints? Every office must have one posted in plain sight, and it is the first thing an OSHA inspector will look for. You can download one from OSHA’s website or order one at no charge by calling 800-321-OSHA.

The poster discusses the “general standards” that all workplaces must comply with to avoid work-related illnesses and injuries. The standards most applicable to medical offices are those dealing with personal protective equipment (PPE), bloodborne pathogens, hazard communication, and – increasingly, of late – ionizing radiation.

Physicians have become all too familiar with the PPE standard as a result of the COVID pandemic. Ironically, OSHA considers PPE a less acceptable means of employee protection than the other standards, as safe work practices should always supersede safety equipment. Nevertheless, employers must have a PPE program in place to train employees on what equipment is necessary, and under which conditions.

You also need a written exposure control plan for bloodborne pathogens. It should document your use of such protective equipment as gloves, face and eye protection, needle guards, and gowns, and your implementation of universal precautions – and it is supposed to be updated annually, to reflect changes in technology. You must provide all at-risk employees with hepatitis B vaccine at no cost to them. You also must provide and pay for appropriate medical treatment and follow-up after any exposure to a dangerous pathogen.

You need not adopt every new safety device as it comes on the market, but you should document which ones you are using – and which you pass up – and why. For example, you and your employees may decide not to purchase a new safety needle because you don’t think it will improve safety, or that it will be more trouble than it’s worth; but you should document how you arrived at that decision, and why you feel that your current protocol is as good or better.

The hazard communication (or right-to-know) standard involves compiling a list of hazardous substances, which all employees have a right to know about. Keep in mind that OSHA’s list includes alcohol, hydrogen peroxide, acetone, liquid nitrogen, and other substances that you might not consider particularly dangerous, but are nevertheless classified as “hazardous.” For each substance, your employees must have access to the manufacturer-supplied Material Safety Data Sheet, which outlines the proper procedures for working with a specific material, and for handling and containing it in a spill or other emergency.

If your office has x-ray equipment, or you are considering one of the new image-guided superficial radiotherapy machines, you must be in compliance with the ionizing radiation standard, which entails shielding, radiation monitors, and clear labeling of equipment.

Other, more general regulations include the physical setup of your office. Everyone must be able to evacuate quickly in case of fire or other emergencies. At a minimum, you (or the owner of the office building) are expected to establish exit routes to accommodate all employees and to post easily visible evacuation diagrams.

Examine all electrical devices and their power sources. All electrically powered equipment – medical, clerical, or anything else in the office – must operate safely. Pay particular attention to the way wall outlets are set up. Make sure each outlet has sufficient power to run the equipment plugged into it, and that circuit breakers are present and functioning. And beware the common situation of too many gadgets running off a single circuit.

Other components of the rule include proper containment of regulated medical waste, identification of regulated-waste containers, sharps disposal boxes, and periodic employee training regarding all of these things.

Federal OSHA regulations do not require medical and dental offices to keep an injury and illness log, as other businesses must; but your state may have a requirement that supersedes the federal law. Check with your state, or with your local OSHA office, regarding any such requirements.

It is a mistake to take OSHA regulations lightly; failure to comply with them can result in stiff penalties running into many thousands of dollars. How can you be certain you are complying with all the rules? The easiest and cheapest way is to call your local OSHA office and request an inspection. Why would you do that? Because OSHA issues no citations during voluntary inspections as long as you agree to remedy any violations they find.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Citrus bergamia (bergamot) is a fruit tree thought to originate in the Mediterranean area; its fruit has been a part of the diet in that region since the early 18th century.¹ Bergamot is known to confer antioxidant as well as anti-inflammatory activity, and yields proapoptotic effects in the sebaceous gland.^2,3 The plant contains the natural furocoumarin bergapten, which is also known as 5-methoxypsoralen.⁴

Antibacterial, anti-inflammatory, hypolipemic, and anticancer properties have been associated with bergapten, which is primarily found in bergamot essential oil and used effectively as a photosensitizing agent.⁵ In this capacity, bergamot oil has been used for photodynamic therapy of cutaneous conditions such as vitiligo.⁶ In fact, for several years 5-methoxypsoralen and 8-methoxypsoralen have been used to achieve acceptable clearance rates of psoriasis and vitiligo.⁷ This column focuses on bergapten, as well as the cutaneous conditions for which bergamot has been shown to have some benefits warranting application or further investigation.
 

Bergapten

In a 2021 literature review, Liang et al. cited the anti-inflammatory, antimicrobial, anticancer, and other salutary effects associated with bergapten. Based on numerous citations, they also cautioned about the phototoxicity of the compound combined with ultraviolet (UV) light while noting the photoactivation of bergapten for anticancer uses.⁴

The following year, Quetglas-Llabrés et al. acknowledged, in another literature review, the numerous preclinical and in vitro studies demonstrating the therapeutic activity of bergapten and highlighted clinical trials revealing notable lesion clearance rates of psoriasis or vitiligo imparted by oral or topical bergapten along with UV irradiation. Bergapten was also found to be effective as hypolipemic therapy.⁵

Anti-inflammatory topical uses

In a 2017 study by Han et al. of 10 essential oils, bergamot was among the investigated oils, all of which exhibited significant anti-proliferative activity in a preinflamed human dermal fibroblast system simulating chronic inflammation. Bergamot was among three essential oils that also suppressed protein molecules involved with inflammation, immune responses, and tissue remodeling, indicating anti-inflammatory and wound healing characteristics.⁸

More recently, Cristiano et al. reported that ultradeformable nanocarriers containing bergamot essential oil and ammonium glycyrrhizinate were demonstrated in healthy human volunteers to be characterized by the appropriate mean size, size distribution, surface charge, and long-term stability for topical administration. Topical administration on human volunteers also revealed greater activity of the combined agents as compared with a nanosystem loaded only with ammonium glycyrrhizinate. The researchers concluded that this combination of ingredients in ultradeformable vesicles shows potential as topical anti-inflammatory treatment.³

Acne

In a 2020 study using golden hamsters, Sun et al. assessed the effects of the juice and essential oils of bergamot and sweet orange on acne vulgaris engendered by excessive androgen secretion. Among 80 male hamsters randomly divided into 10 groups ranging from low to high doses, all results demonstrated improvement with treatment as seen by decreased growth rates of sebaceous glands, suppressed triglyceride accumulation, lowered inflammatory cytokine release, and apoptosis promotion in sebaceous glands. The authors noted that the essential oils yielded better dose-dependent effects than the juices.²

Psoriasis

In 2019, Perna et al. conducted a literature review on the effects of bergamot essential oil, extract, juice, and polyphenolic fraction on various health metrics. Thirty-one studies (20 involving humans with 1,709 subjects and 11 in rats and mice) were identified. Animal models indicated that bergamot essential oil (10 mg/kg or 20 mg/kg daily for 20 weeks) reduced psoriatic plaques, increased skin collagen content, and fostered hair growth and that bergamot juice (20 mg/kg) diminished proinflammatory cytokines. Human studies showed that bergamot extract and essential oil may reduce blood pressure and improve mental conditions.⁹

Vitiligo

In 2019, Shaaban et al. prepared elastic nanocarriers (spanlastics) to deliver psoralen-containing bergamot oil along with PUVB with the intention of harnessing melanogenic activity to treat vitiligo. Histopathologic assessment on rat skin was conducted before clinical treatment in patients with vitiligo. The spanlastics were deemed to be of suitable nanosize and deformable, yielding consistent bergamot oil release. The bergamot oil included in the nanocarrier was found to enhance photostability and photodynamic activity, with the researchers concluding that bergamot oil nanospanlastics with psoralen-UVB therapy shows potential as a vitiligo therapy.¹⁰

Two years later, Shaaban evaluated bergamot oil formulated in nanostructured lipid carriers as a photosensitizer for photodynamic treatment of vitiligo. The botanical oil was effectively used in the nanostructured lipid carriers with a gel consistency that delivered sustained release of the oil for 24 hours. Preclinical and clinical results in patients were encouraging for the topical photodynamic treatment of vitiligo, with the nanostructured lipid carriers improving the photostability and photodynamic activity of bergamot oil.⁶

Photoaging, photoprotection, and safety concerns

Three decades ago, an international cooperative study of the photophysical, photomutagenic, and photocarcinogenic characteristics of bergamot oil and the effect of UVA and UVB sunscreens found that UVB and UVA sunscreens at low concentration (0.5%-1%) in perfumes could not inhibit the phototoxicity of bergamot oil on human skin.¹¹

In a 2015 study assessing the impact of 38% bergamot polyphenolic fraction (a highly concentrated Citrus bergamia fruit extract) on UVB-generated photoaging, Nisticò et al. found that the bergamot compound dose-dependently protected HaCaT cells against UVB-caused oxidative stress and photoaging markers. Suggesting that the high-antioxidant bergamot polyphenolic fraction has potential for use in skin care formulations, the researchers added that the extract seems to induce antiproliferative, immune-modulating, and antiaging activity.¹²In 2022, Alexa et al. performed in vitro tests and found that natural preparations containing bergamot, orange, and clove essential oils do not significantly alter physiological skin parameters and were deemed safe for topical use. An emulsion with bergamot essential oil was also found to reduce the viability of oral squamous cell carcinoma cells.¹³

Conclusion

As a photosensitizing agent, bergamot has an established role in skin care. Beyond its niche role in treatments for vitiligo and psoriasis, this botanical product appears to show potential as an anti-inflammatory agent as well as an ingredient to combat photoaging and skin cancer. Much more research is needed to elucidate the possible wider benefits of this Mediterranean staple.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Juber M. Health benefits of bergamot. WebMD. November 29, 2022. Accessed March 21, 2023.

2. Sun P et al. Mediators Inflamm. 2020 Oct 6;2020:8868107.

3. Cristiano MC et al. Biomedicines. 2022 Apr 30;10(5):1039.

4. Liang Y et al. Phytother Res. 2021 Nov;35(11):6131-47.

5. Quetglas-Llabrés MM et al. Oxid Med Cell Longev. 2022 Apr 25;2022:8615242.

6. Shaaban M et al. Expert Opin Drug Deliv. 2021 Jan;18(1):139-50.

7. McNeely W, Goa KL. Drugs. 1998 Oct;56(4):667-90.

8. Han X, Beaumont C, Stevens N. Biochim Open. 2017 Apr 26;5:1-7.

9. Perna S et al. Food Sci Nutr. 2019 Jan 25;7(2):369-84.

10. Shaaban M et al. Drug Deliv Transl Res. 2019 Dec;9(6):1106-16.

11. Dubertret L et al. J Photochem Photobiol B. 1990 Nov;7(2-4):251-9.

12. Nisticò S et al. J Biol Regul Homeost Agents. 2015 Jul-Sep;29(3):723-8.

13. Alexa VT et al. Molecules. 2022 Feb 1;27(3):990.

Citrus bergamia (bergamot) is a fruit tree thought to originate in the Mediterranean area; its fruit has been a part of the diet in that region since the early 18th century.¹ Bergamot is known to confer antioxidant as well as anti-inflammatory activity, and yields proapoptotic effects in the sebaceous gland.^2,3 The plant contains the natural furocoumarin bergapten, which is also known as 5-methoxypsoralen.⁴

Antibacterial, anti-inflammatory, hypolipemic, and anticancer properties have been associated with bergapten, which is primarily found in bergamot essential oil and used effectively as a photosensitizing agent.⁵ In this capacity, bergamot oil has been used for photodynamic therapy of cutaneous conditions such as vitiligo.⁶ In fact, for several years 5-methoxypsoralen and 8-methoxypsoralen have been used to achieve acceptable clearance rates of psoriasis and vitiligo.⁷ This column focuses on bergapten, as well as the cutaneous conditions for which bergamot has been shown to have some benefits warranting application or further investigation.
 

Bergapten

In a 2021 literature review, Liang et al. cited the anti-inflammatory, antimicrobial, anticancer, and other salutary effects associated with bergapten. Based on numerous citations, they also cautioned about the phototoxicity of the compound combined with ultraviolet (UV) light while noting the photoactivation of bergapten for anticancer uses.⁴

The following year, Quetglas-Llabrés et al. acknowledged, in another literature review, the numerous preclinical and in vitro studies demonstrating the therapeutic activity of bergapten and highlighted clinical trials revealing notable lesion clearance rates of psoriasis or vitiligo imparted by oral or topical bergapten along with UV irradiation. Bergapten was also found to be effective as hypolipemic therapy.⁵

Anti-inflammatory topical uses

In a 2017 study by Han et al. of 10 essential oils, bergamot was among the investigated oils, all of which exhibited significant anti-proliferative activity in a preinflamed human dermal fibroblast system simulating chronic inflammation. Bergamot was among three essential oils that also suppressed protein molecules involved with inflammation, immune responses, and tissue remodeling, indicating anti-inflammatory and wound healing characteristics.⁸

More recently, Cristiano et al. reported that ultradeformable nanocarriers containing bergamot essential oil and ammonium glycyrrhizinate were demonstrated in healthy human volunteers to be characterized by the appropriate mean size, size distribution, surface charge, and long-term stability for topical administration. Topical administration on human volunteers also revealed greater activity of the combined agents as compared with a nanosystem loaded only with ammonium glycyrrhizinate. The researchers concluded that this combination of ingredients in ultradeformable vesicles shows potential as topical anti-inflammatory treatment.³

Acne

In a 2020 study using golden hamsters, Sun et al. assessed the effects of the juice and essential oils of bergamot and sweet orange on acne vulgaris engendered by excessive androgen secretion. Among 80 male hamsters randomly divided into 10 groups ranging from low to high doses, all results demonstrated improvement with treatment as seen by decreased growth rates of sebaceous glands, suppressed triglyceride accumulation, lowered inflammatory cytokine release, and apoptosis promotion in sebaceous glands. The authors noted that the essential oils yielded better dose-dependent effects than the juices.²

Psoriasis

In 2019, Perna et al. conducted a literature review on the effects of bergamot essential oil, extract, juice, and polyphenolic fraction on various health metrics. Thirty-one studies (20 involving humans with 1,709 subjects and 11 in rats and mice) were identified. Animal models indicated that bergamot essential oil (10 mg/kg or 20 mg/kg daily for 20 weeks) reduced psoriatic plaques, increased skin collagen content, and fostered hair growth and that bergamot juice (20 mg/kg) diminished proinflammatory cytokines. Human studies showed that bergamot extract and essential oil may reduce blood pressure and improve mental conditions.⁹

Vitiligo

In 2019, Shaaban et al. prepared elastic nanocarriers (spanlastics) to deliver psoralen-containing bergamot oil along with PUVB with the intention of harnessing melanogenic activity to treat vitiligo. Histopathologic assessment on rat skin was conducted before clinical treatment in patients with vitiligo. The spanlastics were deemed to be of suitable nanosize and deformable, yielding consistent bergamot oil release. The bergamot oil included in the nanocarrier was found to enhance photostability and photodynamic activity, with the researchers concluding that bergamot oil nanospanlastics with psoralen-UVB therapy shows potential as a vitiligo therapy.¹⁰

Two years later, Shaaban evaluated bergamot oil formulated in nanostructured lipid carriers as a photosensitizer for photodynamic treatment of vitiligo. The botanical oil was effectively used in the nanostructured lipid carriers with a gel consistency that delivered sustained release of the oil for 24 hours. Preclinical and clinical results in patients were encouraging for the topical photodynamic treatment of vitiligo, with the nanostructured lipid carriers improving the photostability and photodynamic activity of bergamot oil.⁶

Photoaging, photoprotection, and safety concerns

Three decades ago, an international cooperative study of the photophysical, photomutagenic, and photocarcinogenic characteristics of bergamot oil and the effect of UVA and UVB sunscreens found that UVB and UVA sunscreens at low concentration (0.5%-1%) in perfumes could not inhibit the phototoxicity of bergamot oil on human skin.¹¹

In a 2015 study assessing the impact of 38% bergamot polyphenolic fraction (a highly concentrated Citrus bergamia fruit extract) on UVB-generated photoaging, Nisticò et al. found that the bergamot compound dose-dependently protected HaCaT cells against UVB-caused oxidative stress and photoaging markers. Suggesting that the high-antioxidant bergamot polyphenolic fraction has potential for use in skin care formulations, the researchers added that the extract seems to induce antiproliferative, immune-modulating, and antiaging activity.¹²In 2022, Alexa et al. performed in vitro tests and found that natural preparations containing bergamot, orange, and clove essential oils do not significantly alter physiological skin parameters and were deemed safe for topical use. An emulsion with bergamot essential oil was also found to reduce the viability of oral squamous cell carcinoma cells.¹³

Conclusion

As a photosensitizing agent, bergamot has an established role in skin care. Beyond its niche role in treatments for vitiligo and psoriasis, this botanical product appears to show potential as an anti-inflammatory agent as well as an ingredient to combat photoaging and skin cancer. Much more research is needed to elucidate the possible wider benefits of this Mediterranean staple.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Juber M. Health benefits of bergamot. WebMD. November 29, 2022. Accessed March 21, 2023.

2. Sun P et al. Mediators Inflamm. 2020 Oct 6;2020:8868107.

3. Cristiano MC et al. Biomedicines. 2022 Apr 30;10(5):1039.

4. Liang Y et al. Phytother Res. 2021 Nov;35(11):6131-47.

5. Quetglas-Llabrés MM et al. Oxid Med Cell Longev. 2022 Apr 25;2022:8615242.

6. Shaaban M et al. Expert Opin Drug Deliv. 2021 Jan;18(1):139-50.

7. McNeely W, Goa KL. Drugs. 1998 Oct;56(4):667-90.

8. Han X, Beaumont C, Stevens N. Biochim Open. 2017 Apr 26;5:1-7.

9. Perna S et al. Food Sci Nutr. 2019 Jan 25;7(2):369-84.

10. Shaaban M et al. Drug Deliv Transl Res. 2019 Dec;9(6):1106-16.

11. Dubertret L et al. J Photochem Photobiol B. 1990 Nov;7(2-4):251-9.

12. Nisticò S et al. J Biol Regul Homeost Agents. 2015 Jul-Sep;29(3):723-8.

13. Alexa VT et al. Molecules. 2022 Feb 1;27(3):990.

Citrus bergamia (bergamot) is a fruit tree thought to originate in the Mediterranean area; its fruit has been a part of the diet in that region since the early 18th century.¹ Bergamot is known to confer antioxidant as well as anti-inflammatory activity, and yields proapoptotic effects in the sebaceous gland.^2,3 The plant contains the natural furocoumarin bergapten, which is also known as 5-methoxypsoralen.⁴

Antibacterial, anti-inflammatory, hypolipemic, and anticancer properties have been associated with bergapten, which is primarily found in bergamot essential oil and used effectively as a photosensitizing agent.⁵ In this capacity, bergamot oil has been used for photodynamic therapy of cutaneous conditions such as vitiligo.⁶ In fact, for several years 5-methoxypsoralen and 8-methoxypsoralen have been used to achieve acceptable clearance rates of psoriasis and vitiligo.⁷ This column focuses on bergapten, as well as the cutaneous conditions for which bergamot has been shown to have some benefits warranting application or further investigation.
 

Bergapten

In a 2021 literature review, Liang et al. cited the anti-inflammatory, antimicrobial, anticancer, and other salutary effects associated with bergapten. Based on numerous citations, they also cautioned about the phototoxicity of the compound combined with ultraviolet (UV) light while noting the photoactivation of bergapten for anticancer uses.⁴

The following year, Quetglas-Llabrés et al. acknowledged, in another literature review, the numerous preclinical and in vitro studies demonstrating the therapeutic activity of bergapten and highlighted clinical trials revealing notable lesion clearance rates of psoriasis or vitiligo imparted by oral or topical bergapten along with UV irradiation. Bergapten was also found to be effective as hypolipemic therapy.⁵

Anti-inflammatory topical uses

In a 2017 study by Han et al. of 10 essential oils, bergamot was among the investigated oils, all of which exhibited significant anti-proliferative activity in a preinflamed human dermal fibroblast system simulating chronic inflammation. Bergamot was among three essential oils that also suppressed protein molecules involved with inflammation, immune responses, and tissue remodeling, indicating anti-inflammatory and wound healing characteristics.⁸

More recently, Cristiano et al. reported that ultradeformable nanocarriers containing bergamot essential oil and ammonium glycyrrhizinate were demonstrated in healthy human volunteers to be characterized by the appropriate mean size, size distribution, surface charge, and long-term stability for topical administration. Topical administration on human volunteers also revealed greater activity of the combined agents as compared with a nanosystem loaded only with ammonium glycyrrhizinate. The researchers concluded that this combination of ingredients in ultradeformable vesicles shows potential as topical anti-inflammatory treatment.³

Acne

In a 2020 study using golden hamsters, Sun et al. assessed the effects of the juice and essential oils of bergamot and sweet orange on acne vulgaris engendered by excessive androgen secretion. Among 80 male hamsters randomly divided into 10 groups ranging from low to high doses, all results demonstrated improvement with treatment as seen by decreased growth rates of sebaceous glands, suppressed triglyceride accumulation, lowered inflammatory cytokine release, and apoptosis promotion in sebaceous glands. The authors noted that the essential oils yielded better dose-dependent effects than the juices.²

Psoriasis

In 2019, Perna et al. conducted a literature review on the effects of bergamot essential oil, extract, juice, and polyphenolic fraction on various health metrics. Thirty-one studies (20 involving humans with 1,709 subjects and 11 in rats and mice) were identified. Animal models indicated that bergamot essential oil (10 mg/kg or 20 mg/kg daily for 20 weeks) reduced psoriatic plaques, increased skin collagen content, and fostered hair growth and that bergamot juice (20 mg/kg) diminished proinflammatory cytokines. Human studies showed that bergamot extract and essential oil may reduce blood pressure and improve mental conditions.⁹

Vitiligo

In 2019, Shaaban et al. prepared elastic nanocarriers (spanlastics) to deliver psoralen-containing bergamot oil along with PUVB with the intention of harnessing melanogenic activity to treat vitiligo. Histopathologic assessment on rat skin was conducted before clinical treatment in patients with vitiligo. The spanlastics were deemed to be of suitable nanosize and deformable, yielding consistent bergamot oil release. The bergamot oil included in the nanocarrier was found to enhance photostability and photodynamic activity, with the researchers concluding that bergamot oil nanospanlastics with psoralen-UVB therapy shows potential as a vitiligo therapy.¹⁰

Two years later, Shaaban evaluated bergamot oil formulated in nanostructured lipid carriers as a photosensitizer for photodynamic treatment of vitiligo. The botanical oil was effectively used in the nanostructured lipid carriers with a gel consistency that delivered sustained release of the oil for 24 hours. Preclinical and clinical results in patients were encouraging for the topical photodynamic treatment of vitiligo, with the nanostructured lipid carriers improving the photostability and photodynamic activity of bergamot oil.⁶

Photoaging, photoprotection, and safety concerns

Three decades ago, an international cooperative study of the photophysical, photomutagenic, and photocarcinogenic characteristics of bergamot oil and the effect of UVA and UVB sunscreens found that UVB and UVA sunscreens at low concentration (0.5%-1%) in perfumes could not inhibit the phototoxicity of bergamot oil on human skin.¹¹

In a 2015 study assessing the impact of 38% bergamot polyphenolic fraction (a highly concentrated Citrus bergamia fruit extract) on UVB-generated photoaging, Nisticò et al. found that the bergamot compound dose-dependently protected HaCaT cells against UVB-caused oxidative stress and photoaging markers. Suggesting that the high-antioxidant bergamot polyphenolic fraction has potential for use in skin care formulations, the researchers added that the extract seems to induce antiproliferative, immune-modulating, and antiaging activity.¹²In 2022, Alexa et al. performed in vitro tests and found that natural preparations containing bergamot, orange, and clove essential oils do not significantly alter physiological skin parameters and were deemed safe for topical use. An emulsion with bergamot essential oil was also found to reduce the viability of oral squamous cell carcinoma cells.¹³

Conclusion

As a photosensitizing agent, bergamot has an established role in skin care. Beyond its niche role in treatments for vitiligo and psoriasis, this botanical product appears to show potential as an anti-inflammatory agent as well as an ingredient to combat photoaging and skin cancer. Much more research is needed to elucidate the possible wider benefits of this Mediterranean staple.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as an ecommerce solution. Write to her at [email protected].

References

1. Juber M. Health benefits of bergamot. WebMD. November 29, 2022. Accessed March 21, 2023.

2. Sun P et al. Mediators Inflamm. 2020 Oct 6;2020:8868107.

3. Cristiano MC et al. Biomedicines. 2022 Apr 30;10(5):1039.

4. Liang Y et al. Phytother Res. 2021 Nov;35(11):6131-47.

5. Quetglas-Llabrés MM et al. Oxid Med Cell Longev. 2022 Apr 25;2022:8615242.

6. Shaaban M et al. Expert Opin Drug Deliv. 2021 Jan;18(1):139-50.

7. McNeely W, Goa KL. Drugs. 1998 Oct;56(4):667-90.

8. Han X, Beaumont C, Stevens N. Biochim Open. 2017 Apr 26;5:1-7.

9. Perna S et al. Food Sci Nutr. 2019 Jan 25;7(2):369-84.

10. Shaaban M et al. Drug Deliv Transl Res. 2019 Dec;9(6):1106-16.

11. Dubertret L et al. J Photochem Photobiol B. 1990 Nov;7(2-4):251-9.

12. Nisticò S et al. J Biol Regul Homeost Agents. 2015 Jul-Sep;29(3):723-8.

13. Alexa VT et al. Molecules. 2022 Feb 1;27(3):990.

PHOENIX – Rapid, effective, and well-tolerated treatment of small cutaneous neurofibromas (cNF) without surgery or scarring is possible, with some tumors completely clearing after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.

“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”

Four treatments vs. controls

For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm² fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.

The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.

All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.

The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”

No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.

Tolerability of treatments

As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.

When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.

“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”

The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”

Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.

“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.

“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”

The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.

 

PHOENIX – Rapid, effective, and well-tolerated treatment of small cutaneous neurofibromas (cNF) without surgery or scarring is possible, with some tumors completely clearing after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.

“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”

Four treatments vs. controls

For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm² fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.

The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.

All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.

The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”

No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.

Tolerability of treatments

As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.

When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.

“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”

The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”

Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.

“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.

“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”

The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.

 

PHOENIX – Rapid, effective, and well-tolerated treatment of small cutaneous neurofibromas (cNF) without surgery or scarring is possible, with some tumors completely clearing after only one treatment, according to preliminary results of an ongoing prospective trial that compared several treatment modalities.

“Neurofibromatosis type 1 is the most common single-gene disease of mankind, but there is so much we have yet to learn about it,” study author Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. Dr. Richey also conducts research for the Wellman Center for Photomedicine and the Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston, and is working with R. Rox Anderson, MD, director of the Wellman Center, on this project. In his words, she said, “the lack of better treatments for cNF is a ‘problem worth solving.’ ”

Four treatments vs. controls

For the study, Dr. Richey and colleagues enrolled 19 adults with a total of 307 cNFs measuring 2-4 mm in size to receive one of four treatments: electrocautery with an insulated radiofrequency needle; 755-nm alexandrite laser with negative pressure (8-mm spot size, 100 J/cm² fluence, 3-ms pulse duration); 980-nm diode laser (delivered via 8-mm sapphire skin-contact window), and intratumoral injection of 10 mg/mL deoxycholic acid at a volume approximately equal to that of the tumor. The average age of the participants was 49 years and 15 were female.

The investigators applied 5% lidocaine/prilocaine for 40 minutes to treatment sites before randomizing the tumors to treatment or to the control arm (no treatment). They compared safety, tolerability (including pain scores), and efficacy of each modality as measured by the change in cNF volume/height via three-dimensional imaging and clinical improvement via physician assessment at 6 months. All 19 participants have completed the 6-month assessment.

All modalities reduced or eliminated some of the cNFs by 6 months after treatment, with statistically significant reductions in height and volume across all four treatments. A wide variation of responses was observed. Specifically, the mean tumor volume changes for each modality, compared with controls, were –33.4% versus –5.1% among those treated with the 755-nm alexandrite laser; –24.9% versus –9.2% among those treated with the 980-nm diode laser, –23.3% versus –0.8% among those treated with insulated-needle radiofrequency coagulation, and –29.4% versus –3.7% among those treated with deoxycholic acid.

The variation in responses “may be due to histologic diversity of cNF or may indicate a need for more fine-tuned dosimetry, or a combination,” Dr. Richey said. “Our future trials will address this. We will also be treating all skin types in our upcoming trials.”

No adverse events categorized as higher than grade 2 occurred in any of the treatment groups, and no signs of regrowth or growth stimulation have been observed to date.

Tolerability of treatments

As for general tolerability, the 980-nm laser treatment caused moderate to severe pain; the alexandrite laser caused mild pain; insulated-needle radiofrequency coagulation caused mild pain, though more than deoxycholic acid injections or alexandrite laser, and pain associated with the deoxycholic acid injections was minimal.

When residual neurofibroma tumor was present histologically, its appearance was similar to that of untreated tumors in controls. There was no evidence of atypia, mitosis, or tumor inflammation, and mild fibrosis was present at the sites of prior tumor.

“It was surprising that all four modalities did work to some extent,” Dr. Richey said, noting that the lack of ulceration with deoxycholic acid injection “was pleasantly surprising.” Treatment with the 980-nm diode laser “was a bit more painful than we anticipated.”

The positive results of this trial has raised “more questions for us to answer. We have three additional trials in the works to fine tune these treatments and optimize dose/delivery, with the end goal of treating younger people.”

Dr. Richey said that she was “amazed” by how motivated the enrollees were to participate in the trial, noting that many patients with cNF undergo general anesthesia to have dozens of tumors surgically removed at once. “They pay $10,000-$20,000 on average out of pocket, as this surgery is considered cosmetic,” she said.

“This very important study could lead to effective, relatively noninvasive, therapy for small neurofibromas,” said Jeffrey S. Dover, MD, codirector of SkinCare Physicians in Chestnut Hill, Mass., who was not involved with the study and was asked to comment on the results.

“Remarkably, all four treatments worked to varying degrees, but of all the treatments, the selective alexandrite laser appeared to achieve the best results. Further study will be needed to see just how effective these treatments are, and to determine the best and safest treatment parameters. Given how common this autosomal dominant disease is, and how disfiguring neurofibromas become as they enlarge, a well-tolerated noninvasive nonsurgical treatment with limited side effects is highly sought after.”

The study, which was named the best clinical abstract at the meeting, was supported by the Neurofibromatosis Therapeutic Acceleration Program. Dr. Anderson is supported in part as the Lancer Endowed Chair in Dermatology at MGH. Dr. Dover reported having no relevant disclosures.

 

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

Current U.S., European, and Australian guidelines recommend 10-mm safety margins for radical excision of primary melanomas, but for patients with early-stage cutaneous melanoma in critical areas of the body, excision with 5-mm margins may not significantly increase risk for recurrence or melanoma-specific mortality (MSM), results of a retrospective study suggest.

Among 1,179 patients with stage T1a melanomas near the face, scalp, external genitalia, or other critical areas, the weighted 10-year local recurrence rate for patients who underwent resection with 10-mm margins was 5.7%, compared with 6.7% for those who had resections with 5-mm margins, a nonsignificant difference.

Weighted 10-year melanoma-specific mortality was 1.8% for patients treated with wide margins, vs. 4.2% for those treated with narrow margins, also a nonsignificant difference. Patients treated with narrow margins did have significantly fewer reconstructive surgeries than patients treated with wide margins, reported Andrea Maurichi, MD, and colleagues at the National Cancer Institute of Italy in Milan.

“Because this association was found in melanomas of the head and neck, acral, and genital sites, there is no plausible reason why it could not be extrapolated to other locations. The findings also support the need for prospective randomized clinical trials to definitively answer the important question about appropriate excision margins for T1a melanoma,” they wrote in the study, published online in JAMA Dermatology.

The authors also found, however, that Breslow thickness greater than 0.4 mm and mitotic rate greater than 1/mm­­² were associated with worse MSM, and that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence.

A melanoma expert who was not involved in the study said that despite these findings, wider margins are always preferable.

“There is always a conversation around these general [critical] areas, but as a rule we try to get larger margins,” said Ryan J. Sullivan, MD, of Mass General Cancer Center in Boston.

In an interview, Dr. Sullivan said that the finding about lower frequency of reconstructive procedures in the narrow margins groups may be more of a concern for younger patients than for the elderly.

Study design

The investigators conducted a retrospective cohort study of consecutive patients aged 18 or older at the National Cancer Institute of Milan who were diagnosed with T1a cutaneous melanoma close to critical areas from 2001 through 2020.

Patients with primary cutaneous melanoma of the head and face areas with functional or cosmetic considerations, acral areas (plantar, palmar, digital and interdigital areas), external genitalia, or periumbilical and perineal areas were eligible for inclusion.

The cohort comprised 1,179 patients with a median age of 50 and equal sex distribution. Of these patients, 626 (53%) had a wide excision, of whom 434 had a linear repair, and 192 had a flap of graft reconstruction. The remaining 553 patients had narrow excisions, 491 with linear repair, and 62 with flap or graft reconstruction.

Analyses were adjusted to account for imbalances between the surgical groups.

The study was supported by the nonprofit foundation Emme Rouge. The authors and Dr. Sullivan reported having no relevant conflicts of interest to disclose.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

PHOENIX – During the incidental treatment of melanocytic nevi during laser hair removal, common clinical changes include regression and decreased size, while common histologic changes include mild atypia and thermal damage, according to results from a systematic review of literature on the topic. To date, no severe cases of severe dysplasia or melanoma have been reported.

“That’s reassuring,” study author Ahuva Cices, MD, said in an interview at the annual conference of the American Society for Laser Medicine and Surgery, where she presented the results during an abstract session. “But, with that in mind, we want to avoid treating nevi with laser hair removal to avoid changes that could be concerning. We also recommend baseline skin exams so we know what we’re looking at before we start treating with lasers, and any changes can be recognized from that baseline status. It’s important to keep an eye out for changes and always be evaluating.”

Doug Brunk/MDedge News

In December of 2022, Dr. Cices, chief dermatology resident at Mount Sinai Health System, New York, searched PubMed for articles that evaluated changes in melanocytic nevi after laser hair removal procedures. She used the search terms “nevi laser hair removal,” “nevi diode,” “nevi long pulse alexandrite,” “nevi long pulse neodymium doped yttrium aluminum garnet,” and “melanoma laser hair removal,” and limited the analysis to English language patient-based reports that discussed incidental treatment of melanocytic nevi while undergoing hair removal with a laser.

Reports excluded from the analysis were those that focused on changes following hair removal with nonlaser devices such as intense pulsed light (IPL), those evaluating nonmelanocytic nevi such as Becker’s nevus or nevus of Ota, and those evaluating the intentional ablation or removal of melanocytic lesions.

The search yielded 10 relevant studies for systematic review: seven case reports or series and three observational trials, two of which were prospective and one retrospective.

The results of the review, according to Dr. Cices, revealed that clinical and dermoscopic changes were noted to present as early as 15 days after treatment and persist to the maximum follow up time, at 3 years. Commonly reported changes included regression, decreased size, laser-induced asymmetry, bleaching, darkening, and altered pattern on dermoscopy. Histologic changes included mild atypia, thermal damage, scar formation, and regression.

“Although some of the clinical and dermoscopic alterations may be concerning for malignancy, to our knowledge, there are no documented cases of malignant transformation of nevi following treatment with laser hair removal,” she wrote in the abstract.

Dr. Cices acknowledged certain limitations of the systematic review, including the low number of relevant reports and their generally small sample size, many of which were limited to single cases.

Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, who was asked to comment on the review, characterized the findings as important because laser hair removal is such a commonly performed procedure.

While the study is limited by the small number of studies on the subject matter, “it brings up an important discussion,” Dr. Ibrahimi said in an interview. “Generally speaking, we know that most hair removal lasers do indeed target melanin pigment and can be absorbed by melanocytes. While the wavelengths used for LHR [laser hair removal] will not result in DNA damage or cause mutations that can lead to melanoma, they can sometimes alter the appearance of pigmented lesions and that may change the dermatologist’s ability to monitor them for atypia,” he noted.

“For that reason, I would recommend all patients see a dermatologist for evaluation of their nevi prior to any treatments and they consider very carefully where they get their laser treatments. If they have any atypical pigmented lesions, then that information should be disclosed with the person performing the laser hair removal procedure particularly if there are lesions that are being specifically monitored.”

Dr. Cices reported having no disclosures. Dr. Ibrahimi disclosed that he is a member of the advisory board for Accure Acne, AbbVie, Cutera, Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies.

Memantine, a drug typically used to treat symptoms of Alzheimer’s disease, is linked to a significant reduction in symptoms of trichotillomania and skin-picking disorder, new research shows.

Results from the double-blind, placebo-controlled trial showed that 61% of participants who received memantine were “much or very much improved,” versus 8% in the placebo group.

“Memantine was far more effective than placebo,” lead investigator Jon Grant, MD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said in an interview. “However, while subjects responded favorably, that didn’t necessarily mean there were no symptoms.”

The study was published online  in the American Journal of Psychiatry.
 

Underrecognized, disabling

The investigators noted that trichotillomania and skin-picking disorder are underrecognized and are often disabling conditions. However, the researchers pointed out that with prevalence rates of 1.7% for trichotillomania and 2.1% for skin-picking disorder, they are not uncommon.

Behavioral therapy that attempts to reverse these habits is considered first-line treatment, but trained therapists are difficult to find. In addition, the investigators wrote that currently, there are no Food and Drug Administration–approved medications for either disorder, and pharmacologic clinical trials are relatively uncommon.

The existing data from double-blind, placebo-controlled studies support the use of the antipsychotic olanzapine, the tricyclic antidepressant clomipramine, and the supplement N-acetyl-L-cysteine (NAC). Dr. Grant also noted that previous drug trials involving patients with trichotillomania have been very short in duration.

Prior research has implicated the glutamate system in repetitive motor habits and the urges that drive them. Memantine, a glutamate receptor antagonist, targets excessive glutamatergic drive. To investigate whether this medication may be beneficial for patients with trichotillomania and skin-picking disorders, the investigators conducted a randomized placebo-controlled trial.

The study included 100 adults (86 women; mean age, 31.4) with trichotillomania, skin-picking disorder, or both; participants received memantine (n = 55) or placebo (n = 45) for 8 weeks; they received memantine 10 mg or placebo for the first 2 weeks, then 20 mg for the next 6 weeks.

The researchers, who were blinded to assignment, assessed participants every 2 weeks using the National Institute of Mental Health Trichotillomania Symptom Severity Scale, which was modified to include questions for skin-picking disorder.

The team also tracked symptoms and behaviors using additional scales, including the Sheehan Disability Scale and the Clinical Global Impressions severity scale.

At the study’s conclusion, 79 patients remained. Of those, 26 of the 43 participants in the memantine group were “very much” or “much” improved (61%), versus 3 of 36 (8%) in the placebo group. (P < .0001)

Six participants in the memantine group experienced complete remission of symptoms, compared with one in the placebo group. There were no differences between the study groups in terms of adverse events.

Study limitations included the relatively short length of the trial for what should be considered a chronic disease, as well as the inclusion of only mildly to moderately symptomatic participants.

Dr. Grant said that he would like to study how memantine works in combination with behavioral therapy.
 

‘Two great options’

Katharine Phillips, MD, professor of psychiatry at Weill Cornell Medicine, New York, said she has been using memantine for “quite some time” to treat her patients with skin-picking disorder, adding that she uses higher doses of the drug than were tested in the study.

She noted that both NAC and memantine affect glutamate, an amino acid in the brain that is likely involved in repetitive physical or motor habits, such as hair pulling and skin picking.

“The good news is that we have two great options” for the treatment of trichotillomania and skin-picking disorder, said Dr. Phillips, and that both are easy to tolerate.

Future research should focus on longer trials of memantine and at higher doses, as well as other glutamate modulators, she said.

The study was funded by departmental research funds at the University of Chicago. Dr. Grant reported receiving research funding from Biohaven Pharmaceuticals and Janssen, as well as yearly compensation from Springer Publishing for his role as editor-in-chief of the Journal of Gambling Studies. He has also received royalties from American Psychiatric Publishing, McGraw Hill, Oxford University Press, and WW Norton. Dr. Phillips reported receiving royalties from American Psychiatric Publishing and an honorarium from the Merck Manual.

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

Memantine, a drug typically used to treat symptoms of Alzheimer’s disease, is linked to a significant reduction in symptoms of trichotillomania and skin-picking disorder, new research shows.

Results from the double-blind, placebo-controlled trial showed that 61% of participants who received memantine were “much or very much improved,” versus 8% in the placebo group.

“Memantine was far more effective than placebo,” lead investigator Jon Grant, MD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said in an interview. “However, while subjects responded favorably, that didn’t necessarily mean there were no symptoms.”

The study was published online  in the American Journal of Psychiatry.
 

Underrecognized, disabling

The investigators noted that trichotillomania and skin-picking disorder are underrecognized and are often disabling conditions. However, the researchers pointed out that with prevalence rates of 1.7% for trichotillomania and 2.1% for skin-picking disorder, they are not uncommon.

Behavioral therapy that attempts to reverse these habits is considered first-line treatment, but trained therapists are difficult to find. In addition, the investigators wrote that currently, there are no Food and Drug Administration–approved medications for either disorder, and pharmacologic clinical trials are relatively uncommon.

The existing data from double-blind, placebo-controlled studies support the use of the antipsychotic olanzapine, the tricyclic antidepressant clomipramine, and the supplement N-acetyl-L-cysteine (NAC). Dr. Grant also noted that previous drug trials involving patients with trichotillomania have been very short in duration.

Prior research has implicated the glutamate system in repetitive motor habits and the urges that drive them. Memantine, a glutamate receptor antagonist, targets excessive glutamatergic drive. To investigate whether this medication may be beneficial for patients with trichotillomania and skin-picking disorders, the investigators conducted a randomized placebo-controlled trial.

The study included 100 adults (86 women; mean age, 31.4) with trichotillomania, skin-picking disorder, or both; participants received memantine (n = 55) or placebo (n = 45) for 8 weeks; they received memantine 10 mg or placebo for the first 2 weeks, then 20 mg for the next 6 weeks.

The researchers, who were blinded to assignment, assessed participants every 2 weeks using the National Institute of Mental Health Trichotillomania Symptom Severity Scale, which was modified to include questions for skin-picking disorder.

The team also tracked symptoms and behaviors using additional scales, including the Sheehan Disability Scale and the Clinical Global Impressions severity scale.

At the study’s conclusion, 79 patients remained. Of those, 26 of the 43 participants in the memantine group were “very much” or “much” improved (61%), versus 3 of 36 (8%) in the placebo group. (P < .0001)

Six participants in the memantine group experienced complete remission of symptoms, compared with one in the placebo group. There were no differences between the study groups in terms of adverse events.

Study limitations included the relatively short length of the trial for what should be considered a chronic disease, as well as the inclusion of only mildly to moderately symptomatic participants.

Dr. Grant said that he would like to study how memantine works in combination with behavioral therapy.
 

‘Two great options’

Katharine Phillips, MD, professor of psychiatry at Weill Cornell Medicine, New York, said she has been using memantine for “quite some time” to treat her patients with skin-picking disorder, adding that she uses higher doses of the drug than were tested in the study.

She noted that both NAC and memantine affect glutamate, an amino acid in the brain that is likely involved in repetitive physical or motor habits, such as hair pulling and skin picking.

“The good news is that we have two great options” for the treatment of trichotillomania and skin-picking disorder, said Dr. Phillips, and that both are easy to tolerate.

Future research should focus on longer trials of memantine and at higher doses, as well as other glutamate modulators, she said.

The study was funded by departmental research funds at the University of Chicago. Dr. Grant reported receiving research funding from Biohaven Pharmaceuticals and Janssen, as well as yearly compensation from Springer Publishing for his role as editor-in-chief of the Journal of Gambling Studies. He has also received royalties from American Psychiatric Publishing, McGraw Hill, Oxford University Press, and WW Norton. Dr. Phillips reported receiving royalties from American Psychiatric Publishing and an honorarium from the Merck Manual.

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

Memantine, a drug typically used to treat symptoms of Alzheimer’s disease, is linked to a significant reduction in symptoms of trichotillomania and skin-picking disorder, new research shows.

Results from the double-blind, placebo-controlled trial showed that 61% of participants who received memantine were “much or very much improved,” versus 8% in the placebo group.

“Memantine was far more effective than placebo,” lead investigator Jon Grant, MD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said in an interview. “However, while subjects responded favorably, that didn’t necessarily mean there were no symptoms.”

The study was published online  in the American Journal of Psychiatry.
 

Underrecognized, disabling

The investigators noted that trichotillomania and skin-picking disorder are underrecognized and are often disabling conditions. However, the researchers pointed out that with prevalence rates of 1.7% for trichotillomania and 2.1% for skin-picking disorder, they are not uncommon.

Behavioral therapy that attempts to reverse these habits is considered first-line treatment, but trained therapists are difficult to find. In addition, the investigators wrote that currently, there are no Food and Drug Administration–approved medications for either disorder, and pharmacologic clinical trials are relatively uncommon.

The existing data from double-blind, placebo-controlled studies support the use of the antipsychotic olanzapine, the tricyclic antidepressant clomipramine, and the supplement N-acetyl-L-cysteine (NAC). Dr. Grant also noted that previous drug trials involving patients with trichotillomania have been very short in duration.

Prior research has implicated the glutamate system in repetitive motor habits and the urges that drive them. Memantine, a glutamate receptor antagonist, targets excessive glutamatergic drive. To investigate whether this medication may be beneficial for patients with trichotillomania and skin-picking disorders, the investigators conducted a randomized placebo-controlled trial.

The study included 100 adults (86 women; mean age, 31.4) with trichotillomania, skin-picking disorder, or both; participants received memantine (n = 55) or placebo (n = 45) for 8 weeks; they received memantine 10 mg or placebo for the first 2 weeks, then 20 mg for the next 6 weeks.

The researchers, who were blinded to assignment, assessed participants every 2 weeks using the National Institute of Mental Health Trichotillomania Symptom Severity Scale, which was modified to include questions for skin-picking disorder.

The team also tracked symptoms and behaviors using additional scales, including the Sheehan Disability Scale and the Clinical Global Impressions severity scale.

At the study’s conclusion, 79 patients remained. Of those, 26 of the 43 participants in the memantine group were “very much” or “much” improved (61%), versus 3 of 36 (8%) in the placebo group. (P < .0001)

Six participants in the memantine group experienced complete remission of symptoms, compared with one in the placebo group. There were no differences between the study groups in terms of adverse events.

Study limitations included the relatively short length of the trial for what should be considered a chronic disease, as well as the inclusion of only mildly to moderately symptomatic participants.

Dr. Grant said that he would like to study how memantine works in combination with behavioral therapy.
 

‘Two great options’

Katharine Phillips, MD, professor of psychiatry at Weill Cornell Medicine, New York, said she has been using memantine for “quite some time” to treat her patients with skin-picking disorder, adding that she uses higher doses of the drug than were tested in the study.

She noted that both NAC and memantine affect glutamate, an amino acid in the brain that is likely involved in repetitive physical or motor habits, such as hair pulling and skin picking.

“The good news is that we have two great options” for the treatment of trichotillomania and skin-picking disorder, said Dr. Phillips, and that both are easy to tolerate.

Future research should focus on longer trials of memantine and at higher doses, as well as other glutamate modulators, she said.

The study was funded by departmental research funds at the University of Chicago. Dr. Grant reported receiving research funding from Biohaven Pharmaceuticals and Janssen, as well as yearly compensation from Springer Publishing for his role as editor-in-chief of the Journal of Gambling Studies. He has also received royalties from American Psychiatric Publishing, McGraw Hill, Oxford University Press, and WW Norton. Dr. Phillips reported receiving royalties from American Psychiatric Publishing and an honorarium from the Merck Manual.

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

The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.

The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.

The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.

FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.

Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.

The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.

The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.

At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .

In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.

As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.

“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.

According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.

The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.

A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.

Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

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

The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.

The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.

The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.

FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.

Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.

The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.

The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.

At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .

In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.

As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.

“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.

According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.

The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.

A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.

Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

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

The Food and Drug Administration on April 13 cleared the first patch to reduce excessive underarm sweating for adults with primary axillary hyperhidrosis.

The single-use, disposable, prescription-only patch will be marketed as Brella. It consists of a sodium sheet with an adhesive overlay. A health care provider applies it to the patient’s underarm for up to 3 minutes and then repeats the process on the other underarm.

The developer, Candesant Biomedical, says the patch uses the company’s patented targeted alkali thermolysis (TAT) technology, which was built on the principle that heat is generated when sodium reacts with water in sweat. “The thermal energy created by the sodium sheet is precisely localized, microtargeting sweat glands to significantly reduce sweat production,” according to the company’s press release announcing the FDA decision.

FDA clearance was based on data from the pivotal randomized, double-blind, multicenter SAHARA study, which indicated that the product is effective and well tolerated.

Patients experienced a reduction in sweat that was maintained for 3 months or longer, according to trial results.

The SAHARA trial results were reported in a late-breaking abstract at the annual meeting of the American Academy of Dermatology in March.

The trial enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (indicating frequent sweating or sweating that always interferes with daily activities). Trial participants were randomly assigned to receive either an active TAT or a sham patch, which was applied for up to 3 minutes.

At the meeting, lead investigator David M. Pariser, MD, a dermatologist practicing in Norfolk, Va., reported that at 4 weeks, 63.6% of patients in the active patch group achieved an HDSS score of 1 or 2, compared with 44.2% of those in the sham treatment group (P = .0332). Also, 43.2% of those in the active-patch group achieved an improvement of 2 points or greater on the HDSS, as compared with 16.3% of those in the sham treatment group (P = .0107) .

In addition, 9.1% of those in the active-patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” Dr. Pariser said at the meeting.

As for adverse events (AEs), 13 patients in the active-patch group experienced AEs at the treatment site. Six patients experienced erythema; four experienced erosion; two experienced burning, itching, or stinging; and one had underarm odor.

“The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” Dr. Pariser said. He noted that most AEs resolved in fewer than 2 weeks, and all AEs were mild to moderate.

According to the International Hyperhidrosis Society, about 1.3 million people in the United States have axillary hyperhidrosis, and about a third report that sweating is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities.

The patch will be available within months in select U.S. markets beginning in late summer. The company says the markets will be listed on its website.

A company representative told this news organization that because it is an in-office procedure, pricing will vary, depending on the practice. “With that said, Candesant expects doctors will charge about the same for one session of the Brella SweatControl Patch as they would for a high-end, in-office facial or chemical peel,” the representative said.

Dr. Pariser is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol-Myers Squibb, the Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

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