Article

Key clinical point: Crisaborole was effective in reducing sleep disturbance in pediatric patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At day 29, a significantly lower proportion of patients reported sleep disturbance in the crisaborole vs vehicle group (48.5% vs 57.7%; P = .001). Crisaborole led to a 32.2% decrease in the proportion of infants with ≥1 night of disturbed sleep.

Study details: This post hoc analysis included infants aged 3 to <24 months (CARE 1; n = 137), patients aged 2 to <16 years (pooled CORE 1/CORE 2; n = 1227), and families of patients aged 2 to <18 years (pooled CORE 1/CORE 2; n = 1313) with mild-to-moderate AD who received crisaborole or vehicle twice daily for 28 days.

Disclosures: This study was sponsored by Pfizer Inc. Some authors declared serving as speakers and consultants for or receiving speaker and consulting fees from various sources, including Pfizer. Six authors declared being employees of and holding stocks in Pfizer Inc.

Source: Fowler J et al. Impact of crisaborole on sleep outcomes in pediatric patients with mild-to-moderate atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Feb 22). Doi: 10.1007/s13555-023-00899-y

Key clinical point: Crisaborole was effective in reducing sleep disturbance in pediatric patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At day 29, a significantly lower proportion of patients reported sleep disturbance in the crisaborole vs vehicle group (48.5% vs 57.7%; P = .001). Crisaborole led to a 32.2% decrease in the proportion of infants with ≥1 night of disturbed sleep.

Study details: This post hoc analysis included infants aged 3 to <24 months (CARE 1; n = 137), patients aged 2 to <16 years (pooled CORE 1/CORE 2; n = 1227), and families of patients aged 2 to <18 years (pooled CORE 1/CORE 2; n = 1313) with mild-to-moderate AD who received crisaborole or vehicle twice daily for 28 days.

Disclosures: This study was sponsored by Pfizer Inc. Some authors declared serving as speakers and consultants for or receiving speaker and consulting fees from various sources, including Pfizer. Six authors declared being employees of and holding stocks in Pfizer Inc.

Source: Fowler J et al. Impact of crisaborole on sleep outcomes in pediatric patients with mild-to-moderate atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Feb 22). Doi: 10.1007/s13555-023-00899-y

Key clinical point: Crisaborole was effective in reducing sleep disturbance in pediatric patients with mild-to-moderate atopic dermatitis (AD).

Major finding: At day 29, a significantly lower proportion of patients reported sleep disturbance in the crisaborole vs vehicle group (48.5% vs 57.7%; P = .001). Crisaborole led to a 32.2% decrease in the proportion of infants with ≥1 night of disturbed sleep.

Study details: This post hoc analysis included infants aged 3 to <24 months (CARE 1; n = 137), patients aged 2 to <16 years (pooled CORE 1/CORE 2; n = 1227), and families of patients aged 2 to <18 years (pooled CORE 1/CORE 2; n = 1313) with mild-to-moderate AD who received crisaborole or vehicle twice daily for 28 days.

Disclosures: This study was sponsored by Pfizer Inc. Some authors declared serving as speakers and consultants for or receiving speaker and consulting fees from various sources, including Pfizer. Six authors declared being employees of and holding stocks in Pfizer Inc.

Source: Fowler J et al. Impact of crisaborole on sleep outcomes in pediatric patients with mild-to-moderate atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Feb 22). Doi: 10.1007/s13555-023-00899-y

Key clinical point: Adult patients with atopic dermatitis (AD) are at an increased risk of developing subsequent gastroesophageal reflux disease (GERD).

Major finding: Patients with AD vs matched control individuals had a 15% higher risk for subsequent GERD (adjusted hazard ratio [aHR] 1.15; P = .0013), with the risk being higher in women (aHR 1.17; P = .0120) vs men (aHR 1.15; P = .0343) with AD.

Study details: The data come from a retrospective population-based cohort study including 9164 patients aged ≥20 years with AD and 9164 matched control individuals without AD.

Disclosures: This study was supported by a grant of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology. The authors declared no conflicts of interest.

Source: Lee SW et al. Atopic dermatitis and risk of gastroesophageal reflux disease: A nationwide population-based study. PLoS One. 2023;18(2):e0281883 (Feb 17). Doi: 10.1371/journal.pone.0281883

Key clinical point: Adult patients with atopic dermatitis (AD) are at an increased risk of developing subsequent gastroesophageal reflux disease (GERD).

Major finding: Patients with AD vs matched control individuals had a 15% higher risk for subsequent GERD (adjusted hazard ratio [aHR] 1.15; P = .0013), with the risk being higher in women (aHR 1.17; P = .0120) vs men (aHR 1.15; P = .0343) with AD.

Study details: The data come from a retrospective population-based cohort study including 9164 patients aged ≥20 years with AD and 9164 matched control individuals without AD.

Disclosures: This study was supported by a grant of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology. The authors declared no conflicts of interest.

Source: Lee SW et al. Atopic dermatitis and risk of gastroesophageal reflux disease: A nationwide population-based study. PLoS One. 2023;18(2):e0281883 (Feb 17). Doi: 10.1371/journal.pone.0281883

Key clinical point: Adult patients with atopic dermatitis (AD) are at an increased risk of developing subsequent gastroesophageal reflux disease (GERD).

Major finding: Patients with AD vs matched control individuals had a 15% higher risk for subsequent GERD (adjusted hazard ratio [aHR] 1.15; P = .0013), with the risk being higher in women (aHR 1.17; P = .0120) vs men (aHR 1.15; P = .0343) with AD.

Study details: The data come from a retrospective population-based cohort study including 9164 patients aged ≥20 years with AD and 9164 matched control individuals without AD.

Disclosures: This study was supported by a grant of the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology. The authors declared no conflicts of interest.

Source: Lee SW et al. Atopic dermatitis and risk of gastroesophageal reflux disease: A nationwide population-based study. PLoS One. 2023;18(2):e0281883 (Feb 17). Doi: 10.1371/journal.pone.0281883

Key clinical point: Environmental conditions characterized by the month of birth affect the risk of developing eczema and atopic dermatitis (AD) in infants until 1 year of age.

Major finding: With infants born in spring as a reference, those born in autumn had the highest risk for eczema at 6 months (adjusted odds ratio [aOR] 2.19; 95% CI 2.10-2.30) and 1 year (aOR 1.08; 95% CI 1.02-1.14) of age and for physician-diagnosed AD up to 1 year of age (aOR 1.33; 95% CI 1.20-1.47), whereas those born in summer had the highest risk for eczema at the age of 1 month (aOR 1.19; 95% CI 1.14-1.24).

Study details: This study analyzed the data of 81,615 infants from a prospective birth cohort study, the Japan Environment and Children’s Study (JECS).

Disclosures: The JECS is supported by the Ministry of the Environment, Japan. The authors declared no conflicts of interest.

Source: Tsuchida A et al. Season of birth and atopic dermatitis in early infancy: Results from the Japan Environment and Children’s Study. BMC Pediatr. 2023;23(1):78 (Feb 15). Doi: 10.1186/s12887-023-03878-6

Key clinical point: Environmental conditions characterized by the month of birth affect the risk of developing eczema and atopic dermatitis (AD) in infants until 1 year of age.

Major finding: With infants born in spring as a reference, those born in autumn had the highest risk for eczema at 6 months (adjusted odds ratio [aOR] 2.19; 95% CI 2.10-2.30) and 1 year (aOR 1.08; 95% CI 1.02-1.14) of age and for physician-diagnosed AD up to 1 year of age (aOR 1.33; 95% CI 1.20-1.47), whereas those born in summer had the highest risk for eczema at the age of 1 month (aOR 1.19; 95% CI 1.14-1.24).

Study details: This study analyzed the data of 81,615 infants from a prospective birth cohort study, the Japan Environment and Children’s Study (JECS).

Disclosures: The JECS is supported by the Ministry of the Environment, Japan. The authors declared no conflicts of interest.

Source: Tsuchida A et al. Season of birth and atopic dermatitis in early infancy: Results from the Japan Environment and Children’s Study. BMC Pediatr. 2023;23(1):78 (Feb 15). Doi: 10.1186/s12887-023-03878-6

Key clinical point: Environmental conditions characterized by the month of birth affect the risk of developing eczema and atopic dermatitis (AD) in infants until 1 year of age.

Major finding: With infants born in spring as a reference, those born in autumn had the highest risk for eczema at 6 months (adjusted odds ratio [aOR] 2.19; 95% CI 2.10-2.30) and 1 year (aOR 1.08; 95% CI 1.02-1.14) of age and for physician-diagnosed AD up to 1 year of age (aOR 1.33; 95% CI 1.20-1.47), whereas those born in summer had the highest risk for eczema at the age of 1 month (aOR 1.19; 95% CI 1.14-1.24).

Study details: This study analyzed the data of 81,615 infants from a prospective birth cohort study, the Japan Environment and Children’s Study (JECS).

Disclosures: The JECS is supported by the Ministry of the Environment, Japan. The authors declared no conflicts of interest.

Source: Tsuchida A et al. Season of birth and atopic dermatitis in early infancy: Results from the Japan Environment and Children’s Study. BMC Pediatr. 2023;23(1):78 (Feb 15). Doi: 10.1186/s12887-023-03878-6

Key clinical point: Patients with atopic dermatitis (AD) who experienced greater pruritus reductions after nemolizumab treatment also showed clinically meaningful improvements in other pruritus and cutaneous symptoms.

Major finding: At week 16, a greater proportion of pruritus Visual Analogy Scale (VAS) responders (≥50% improvement) vs nonresponders achieved a pruritus VAS score of <30 mm (81.6% vs 0%), ≥50% improvement in the Eczema Area and Severity Index score (65.3% vs 44.7%), ≥4-point improvement in pruritus numerical rating scale score (89.6% vs 2.1%), and 5-level itch score of ≤1 (42.9% vs 3.2%).

Study details: This post hoc analysis of the Nemolizumab-JP01 study Part A included 215 patients with inadequately controlled AD who had been randomly assigned to receive subcutaneous 60 mg nemolizumab (n = 143) or placebo (n = 72) every 4 weeks for 16 weeks.

Disclosures: This study was funded by Maruho. Some authors declared receiving grants or personal fees from various organizations, including Maruho. Two authors declared being employees of Maruho.

Source: Kabashima K et al for the Nemolizumab-JP01 Study Group. Clinically meaningful improvements in cutaneous lesions and quality of life measures in patients with atopic dermatitis with greater pruritus reductions after treatment with 60 mg nemolizumab subcutaneously every 4 weeks: Subgroup analysis from a phase 3, randomized, controlled trial. J Dermatolog Treat. 2023;1-13 (Feb 13). Doi: 10.1080/09546634.2023.2177096

Key clinical point: Patients with atopic dermatitis (AD) who experienced greater pruritus reductions after nemolizumab treatment also showed clinically meaningful improvements in other pruritus and cutaneous symptoms.

Major finding: At week 16, a greater proportion of pruritus Visual Analogy Scale (VAS) responders (≥50% improvement) vs nonresponders achieved a pruritus VAS score of <30 mm (81.6% vs 0%), ≥50% improvement in the Eczema Area and Severity Index score (65.3% vs 44.7%), ≥4-point improvement in pruritus numerical rating scale score (89.6% vs 2.1%), and 5-level itch score of ≤1 (42.9% vs 3.2%).

Study details: This post hoc analysis of the Nemolizumab-JP01 study Part A included 215 patients with inadequately controlled AD who had been randomly assigned to receive subcutaneous 60 mg nemolizumab (n = 143) or placebo (n = 72) every 4 weeks for 16 weeks.

Disclosures: This study was funded by Maruho. Some authors declared receiving grants or personal fees from various organizations, including Maruho. Two authors declared being employees of Maruho.

Source: Kabashima K et al for the Nemolizumab-JP01 Study Group. Clinically meaningful improvements in cutaneous lesions and quality of life measures in patients with atopic dermatitis with greater pruritus reductions after treatment with 60 mg nemolizumab subcutaneously every 4 weeks: Subgroup analysis from a phase 3, randomized, controlled trial. J Dermatolog Treat. 2023;1-13 (Feb 13). Doi: 10.1080/09546634.2023.2177096

Key clinical point: Patients with atopic dermatitis (AD) who experienced greater pruritus reductions after nemolizumab treatment also showed clinically meaningful improvements in other pruritus and cutaneous symptoms.

Major finding: At week 16, a greater proportion of pruritus Visual Analogy Scale (VAS) responders (≥50% improvement) vs nonresponders achieved a pruritus VAS score of <30 mm (81.6% vs 0%), ≥50% improvement in the Eczema Area and Severity Index score (65.3% vs 44.7%), ≥4-point improvement in pruritus numerical rating scale score (89.6% vs 2.1%), and 5-level itch score of ≤1 (42.9% vs 3.2%).

Study details: This post hoc analysis of the Nemolizumab-JP01 study Part A included 215 patients with inadequately controlled AD who had been randomly assigned to receive subcutaneous 60 mg nemolizumab (n = 143) or placebo (n = 72) every 4 weeks for 16 weeks.

Disclosures: This study was funded by Maruho. Some authors declared receiving grants or personal fees from various organizations, including Maruho. Two authors declared being employees of Maruho.

Source: Kabashima K et al for the Nemolizumab-JP01 Study Group. Clinically meaningful improvements in cutaneous lesions and quality of life measures in patients with atopic dermatitis with greater pruritus reductions after treatment with 60 mg nemolizumab subcutaneously every 4 weeks: Subgroup analysis from a phase 3, randomized, controlled trial. J Dermatolog Treat. 2023;1-13 (Feb 13). Doi: 10.1080/09546634.2023.2177096

Key clinical point: Use of e-cigarettes is significantly associated with the development of atopic dermatitis (AD) in the US adult population.

Major finding: E-cigarette use was significantly associated with AD (adjusted odds ratio 1.35; P < .001). The association was significant in women (P < .001) but not in men (P = .5).

Study details: This population-based study analyzed the data of 28,563 adults from the US National Health Interview Survey 2021.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants, speakers, investigators, or advisors for or receiving speaking fees from various organizations.

Source: Smith B et al. Association between electronic cigarette use and atopic dermatitis among United States adults. J Am Acad Dermatol. 2023 (Feb 24). Doi: 10.1016/j.jaad.2023.02.027.

Key clinical point: Use of e-cigarettes is significantly associated with the development of atopic dermatitis (AD) in the US adult population.

Major finding: E-cigarette use was significantly associated with AD (adjusted odds ratio 1.35; P < .001). The association was significant in women (P < .001) but not in men (P = .5).

Study details: This population-based study analyzed the data of 28,563 adults from the US National Health Interview Survey 2021.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants, speakers, investigators, or advisors for or receiving speaking fees from various organizations.

Source: Smith B et al. Association between electronic cigarette use and atopic dermatitis among United States adults. J Am Acad Dermatol. 2023 (Feb 24). Doi: 10.1016/j.jaad.2023.02.027.

Key clinical point: Use of e-cigarettes is significantly associated with the development of atopic dermatitis (AD) in the US adult population.

Major finding: E-cigarette use was significantly associated with AD (adjusted odds ratio 1.35; P < .001). The association was significant in women (P < .001) but not in men (P = .5).

Study details: This population-based study analyzed the data of 28,563 adults from the US National Health Interview Survey 2021.

Disclosures: This study did not receive any funding. Some authors declared serving as consultants, speakers, investigators, or advisors for or receiving speaking fees from various organizations.

Source: Smith B et al. Association between electronic cigarette use and atopic dermatitis among United States adults. J Am Acad Dermatol. 2023 (Feb 24). Doi: 10.1016/j.jaad.2023.02.027.

Key clinical point: After patch testing, the frequency of allergic contact dermatitis (ACD) diagnosis was higher among patients with atopic dermatitis (AD) than among individuals without AD.

Major finding: Among patients with AD vs individuals without AD, the diagnosis rate of ACD (54.8% vs 47.3%; P < .0001), particularly ACD to cosmetics (7.0% vs 5.7%; P = .0007), medicaments (2.3% vs 1.7%; P = .02), dyes (1.9% vs 1.4%; P = .036), and foods contacting the skin (0.4% vs 0.1%; P = .003), was significantly higher.

Study details: This retrospective study included 15,737 individuals who underwent patch testing, of which 5641 were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Qian MF et al. Prevalence of allergic contact dermatitis following patch testing in patients with atopic dermatitis: A retrospective United States claims-based study. J Am Acad Dermatol. 2023 (Feb 10). Doi: 10.1016/j.jaad.2022.12.051

Key clinical point: After patch testing, the frequency of allergic contact dermatitis (ACD) diagnosis was higher among patients with atopic dermatitis (AD) than among individuals without AD.

Major finding: Among patients with AD vs individuals without AD, the diagnosis rate of ACD (54.8% vs 47.3%; P < .0001), particularly ACD to cosmetics (7.0% vs 5.7%; P = .0007), medicaments (2.3% vs 1.7%; P = .02), dyes (1.9% vs 1.4%; P = .036), and foods contacting the skin (0.4% vs 0.1%; P = .003), was significantly higher.

Study details: This retrospective study included 15,737 individuals who underwent patch testing, of which 5641 were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Qian MF et al. Prevalence of allergic contact dermatitis following patch testing in patients with atopic dermatitis: A retrospective United States claims-based study. J Am Acad Dermatol. 2023 (Feb 10). Doi: 10.1016/j.jaad.2022.12.051

Key clinical point: After patch testing, the frequency of allergic contact dermatitis (ACD) diagnosis was higher among patients with atopic dermatitis (AD) than among individuals without AD.

Major finding: Among patients with AD vs individuals without AD, the diagnosis rate of ACD (54.8% vs 47.3%; P < .0001), particularly ACD to cosmetics (7.0% vs 5.7%; P = .0007), medicaments (2.3% vs 1.7%; P = .02), dyes (1.9% vs 1.4%; P = .036), and foods contacting the skin (0.4% vs 0.1%; P = .003), was significantly higher.

Study details: This retrospective study included 15,737 individuals who underwent patch testing, of which 5641 were diagnosed with AD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Qian MF et al. Prevalence of allergic contact dermatitis following patch testing in patients with atopic dermatitis: A retrospective United States claims-based study. J Am Acad Dermatol. 2023 (Feb 10). Doi: 10.1016/j.jaad.2022.12.051

Key clinical point: In real-life settings, upadacitinib was effective and safe in patients with moderate-to-severe atopic dermatitis (AD), including those with prior inadequate response to dupilumab or baricitinib.

Major finding: At week 16, the mean Eczema Area and Severity Index and Numerical Rating Scale pruritus scores decreased significantly from 16.6 to 5.7 and 7.0 to 3.7, respectively (both P < .001), with rapid improvement being observed in the first 4 weeks. Adverse events were mostly mild in severity.

Study details: This prospective multicenter observational study included 47 adult patients with moderate-to-severe AD from the Dutch BioDay registry who received upadacitinib (15 or 30 mg once daily), of which 23 and 14 had not or inadequately responded to previous dupilumab and baricitinib therapies, respectively.

Disclosures: The BioDay registry is sponsored by Eli Lilly and others. Some authors reported ties with various sources, including the BioDay registry sponsors.

Source: Boesjes CM et al. Effectiveness of upadacitinib in patients with atopic dermatitis including those with inadequate response to dupilumab and/or baricitinib: Results from the BioDay Registry. Acta Derm Venereol. 2023;103:adv00872 (Feb 16). Doi: 10.2340/actadv.v103.5243

Key clinical point: In real-life settings, upadacitinib was effective and safe in patients with moderate-to-severe atopic dermatitis (AD), including those with prior inadequate response to dupilumab or baricitinib.

Major finding: At week 16, the mean Eczema Area and Severity Index and Numerical Rating Scale pruritus scores decreased significantly from 16.6 to 5.7 and 7.0 to 3.7, respectively (both P < .001), with rapid improvement being observed in the first 4 weeks. Adverse events were mostly mild in severity.

Study details: This prospective multicenter observational study included 47 adult patients with moderate-to-severe AD from the Dutch BioDay registry who received upadacitinib (15 or 30 mg once daily), of which 23 and 14 had not or inadequately responded to previous dupilumab and baricitinib therapies, respectively.

Disclosures: The BioDay registry is sponsored by Eli Lilly and others. Some authors reported ties with various sources, including the BioDay registry sponsors.

Source: Boesjes CM et al. Effectiveness of upadacitinib in patients with atopic dermatitis including those with inadequate response to dupilumab and/or baricitinib: Results from the BioDay Registry. Acta Derm Venereol. 2023;103:adv00872 (Feb 16). Doi: 10.2340/actadv.v103.5243

Key clinical point: In real-life settings, upadacitinib was effective and safe in patients with moderate-to-severe atopic dermatitis (AD), including those with prior inadequate response to dupilumab or baricitinib.

Major finding: At week 16, the mean Eczema Area and Severity Index and Numerical Rating Scale pruritus scores decreased significantly from 16.6 to 5.7 and 7.0 to 3.7, respectively (both P < .001), with rapid improvement being observed in the first 4 weeks. Adverse events were mostly mild in severity.

Study details: This prospective multicenter observational study included 47 adult patients with moderate-to-severe AD from the Dutch BioDay registry who received upadacitinib (15 or 30 mg once daily), of which 23 and 14 had not or inadequately responded to previous dupilumab and baricitinib therapies, respectively.

Disclosures: The BioDay registry is sponsored by Eli Lilly and others. Some authors reported ties with various sources, including the BioDay registry sponsors.

Source: Boesjes CM et al. Effectiveness of upadacitinib in patients with atopic dermatitis including those with inadequate response to dupilumab and/or baricitinib: Results from the BioDay Registry. Acta Derm Venereol. 2023;103:adv00872 (Feb 16). Doi: 10.2340/actadv.v103.5243

Key clinical point: Dupilumab is safe and improves atopic dermatitis (AD) signs and symptoms in patients aged ≥60 years with moderate-to-severe AD.

Major finding: At week 16, similar to the <60-year group, a significantly higher proportion of patients receiving dupilumab (every 2 weeks or every week) vs placebo in the ≥60-year group achieved an Investigator’s Global Assessment score of 0 or 1 (44.4% or 39.7% vs 7.1%, respectively; both P < .0001) and a 75% improvement in the Eczema Area and Severity Index (63.0% or 61.6% vs 14.3%, respectively; both P < .0001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: This post hoc pooled analysis of four phase 3 trials included 2444 patients (≥60 years, n = 183; <60 years, n = 2261) with moderate-to-severe AD who were randomly assigned to receive dupilumab or placebo.

Disclosures: This study was funded by Sanofi-Regeneron Pharmaceuticals Inc. Some authors reported various ties, including employment, with Sanofi, Regeneron, or others.

Source: Silverberg JI et al. Efficacy and safety of dupilumab maintained in adults ≥ 60 years of age with moderate-to-severe atopic dermatitis: Analysis of pooled data from four randomized clinical trials. Am J Clin Dermatol. 2023 (Feb 20). Doi: 10.1007/s40257-022-00754-4

Key clinical point: Dupilumab is safe and improves atopic dermatitis (AD) signs and symptoms in patients aged ≥60 years with moderate-to-severe AD.

Major finding: At week 16, similar to the <60-year group, a significantly higher proportion of patients receiving dupilumab (every 2 weeks or every week) vs placebo in the ≥60-year group achieved an Investigator’s Global Assessment score of 0 or 1 (44.4% or 39.7% vs 7.1%, respectively; both P < .0001) and a 75% improvement in the Eczema Area and Severity Index (63.0% or 61.6% vs 14.3%, respectively; both P < .0001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: This post hoc pooled analysis of four phase 3 trials included 2444 patients (≥60 years, n = 183; <60 years, n = 2261) with moderate-to-severe AD who were randomly assigned to receive dupilumab or placebo.

Disclosures: This study was funded by Sanofi-Regeneron Pharmaceuticals Inc. Some authors reported various ties, including employment, with Sanofi, Regeneron, or others.

Source: Silverberg JI et al. Efficacy and safety of dupilumab maintained in adults ≥ 60 years of age with moderate-to-severe atopic dermatitis: Analysis of pooled data from four randomized clinical trials. Am J Clin Dermatol. 2023 (Feb 20). Doi: 10.1007/s40257-022-00754-4

Key clinical point: Dupilumab is safe and improves atopic dermatitis (AD) signs and symptoms in patients aged ≥60 years with moderate-to-severe AD.

Major finding: At week 16, similar to the <60-year group, a significantly higher proportion of patients receiving dupilumab (every 2 weeks or every week) vs placebo in the ≥60-year group achieved an Investigator’s Global Assessment score of 0 or 1 (44.4% or 39.7% vs 7.1%, respectively; both P < .0001) and a 75% improvement in the Eczema Area and Severity Index (63.0% or 61.6% vs 14.3%, respectively; both P < .0001). Most treatment-emergent adverse events were of mild-to-moderate severity.

Study details: This post hoc pooled analysis of four phase 3 trials included 2444 patients (≥60 years, n = 183; <60 years, n = 2261) with moderate-to-severe AD who were randomly assigned to receive dupilumab or placebo.

Disclosures: This study was funded by Sanofi-Regeneron Pharmaceuticals Inc. Some authors reported various ties, including employment, with Sanofi, Regeneron, or others.

Source: Silverberg JI et al. Efficacy and safety of dupilumab maintained in adults ≥ 60 years of age with moderate-to-severe atopic dermatitis: Analysis of pooled data from four randomized clinical trials. Am J Clin Dermatol. 2023 (Feb 20). Doi: 10.1007/s40257-022-00754-4

The restrictive therapeutic index of chemotherapy has led to the emergence of antibody-drug conjugates (ADCs), medicines that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxic effects of chemotherapy to deliver cytotoxic payloads to cancer cells. This targeted approach can reduce the side effects of chemotherapy and improve the effectiveness of treatment. Several ADCs, including ado-trastuzumab emtansine (Kadcyla), sacituzumab govitecan-hziy (Trodelvy), and fam-trastuzumab deruxtecan-nxki (Enhertu), are currently approved for treating some types of breast cancer (BC).

The ADC trastuzumab emtansine was approved specifically for treating human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in patients who have previously been treated with trastuzumab and a taxane (paclitaxel or docetaxel) and who have already been treated for mBC or have developed tumor recurrence within 6 months of receiving adjuvant therapy. The US Food and Drug Administration (FDA) approval was based on the results of the EMILIA study, a phase 3 clinical trial that compared treatment with trastuzumab emtansine vs capecitabine + lapatinib in participants with HER2+, locally advanced, or metastatic BC. This trial emerged from the need for well-tolerated, HER2-directed therapies for patients with this type of cancer. Trastuzumab emtansine consists of trastuzumab, a mAb that targets HER2 (which is overexpressed in about 20% of BCs), linked to emtansine, a cytotoxic payload that inhibits cell division. The trastuzumab emtansine group had a median overall survival (OS) of 29.9 months vs 25.9 months in the capecitabine + lapatinib group, for a hazard ratio (HR) of 0.75 (95% CI: 0.64, 0.88). 

Another ADC, sacituzumab govitecan, targets the Trop-2 protein, which is overexpressed in BC. This ADC includes a mAb that is linked to SN-38, a cytotoxic payload that inhibits DNA replication. Triple-negative breast cancer (TNBC) is a subtype of BC that does not have receptors for estrogen, progesterone, or HER2—making it more difficult to treat than other forms of BC. Sacituzumab govitecan is used to treat patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease. Sacituzumab govitecan is also approved for the treatment of patients with unresectable locally advanced or metastatic hormone-receptor–positive (HR+), and HER2-negative (HER2−) BC who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting. Sacituzumab govitecan was the first Trop-2–directed ADC to demonstrate OS benefit in patients with HR+/HER2− mBC who had received prior endocrine-based therapy and at least 2 chemotherapies. It is now also recommended as a Category 1 preferred treatment for metastatic HR+/HER2− BC by the National Comprehensive Cancer Network.

The results of the TROPiCS-02 study, which led to the FDA approval of sacituzumab govitecan, demonstrated a median OS of 14.4 months with sacituzumab govitecan vs 11.2 months with treatment of physician’s choice (HR, 0.79; 95% CI: 0.65, 0.96; P = 0.02). This represents a 3.2-month improvement in survival and a 21% reduction in the risk for patient death. Before this medicine was approved, there were limited options to offer patients with BC after endocrine-based therapy and chemotherapy.

A third ADC, trastuzumab deruxtecan, targets the HER2 protein, like trastuzumab emtansine, but with a different cytotoxic payload. It consists of trastuzumab linked to deruxtecan, whose cytotoxicity inhibits DNA replication. It is approved for the treatment of HER2+ mBC. Its FDA approval was based on the results of the DESTINY-Breast04  phase 3 clinical trial, which demonstrated that treatment with trastuzumab deruxtecan, when compared with standard-of-care chemotherapy, doubles progression-free survival among patients with mBC that expresses low levels of HER2. The median OS for patients in the HR+ group who received trastuzumab deruxtecan was 23.9 months vs 17.5 months for those who received chemotherapy. In the hormone receptor-negative (HR−) group, the median OS for those who took trastuzumab deruxtecan was 16.6 months vs 10.3 months for those treated with chemotherapy. 

The emergence of ADCs have demonstrated promising advancements in the treatment of BC, particularly in patients with HER2+ or triple-negative disease. ADCs have given new hope to and prolonged life for patients living with pretreated HR+/HER2− mBC. ADCs also have the potential to provide a more effective and less toxic treatment option for patients with BC. However, further research is needed to fully understand their long-term effects and to develop new ADCs that target other types of BC.

The restrictive therapeutic index of chemotherapy has led to the emergence of antibody-drug conjugates (ADCs), medicines that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxic effects of chemotherapy to deliver cytotoxic payloads to cancer cells. This targeted approach can reduce the side effects of chemotherapy and improve the effectiveness of treatment. Several ADCs, including ado-trastuzumab emtansine (Kadcyla), sacituzumab govitecan-hziy (Trodelvy), and fam-trastuzumab deruxtecan-nxki (Enhertu), are currently approved for treating some types of breast cancer (BC).

The ADC trastuzumab emtansine was approved specifically for treating human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in patients who have previously been treated with trastuzumab and a taxane (paclitaxel or docetaxel) and who have already been treated for mBC or have developed tumor recurrence within 6 months of receiving adjuvant therapy. The US Food and Drug Administration (FDA) approval was based on the results of the EMILIA study, a phase 3 clinical trial that compared treatment with trastuzumab emtansine vs capecitabine + lapatinib in participants with HER2+, locally advanced, or metastatic BC. This trial emerged from the need for well-tolerated, HER2-directed therapies for patients with this type of cancer. Trastuzumab emtansine consists of trastuzumab, a mAb that targets HER2 (which is overexpressed in about 20% of BCs), linked to emtansine, a cytotoxic payload that inhibits cell division. The trastuzumab emtansine group had a median overall survival (OS) of 29.9 months vs 25.9 months in the capecitabine + lapatinib group, for a hazard ratio (HR) of 0.75 (95% CI: 0.64, 0.88). 

Another ADC, sacituzumab govitecan, targets the Trop-2 protein, which is overexpressed in BC. This ADC includes a mAb that is linked to SN-38, a cytotoxic payload that inhibits DNA replication. Triple-negative breast cancer (TNBC) is a subtype of BC that does not have receptors for estrogen, progesterone, or HER2—making it more difficult to treat than other forms of BC. Sacituzumab govitecan is used to treat patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease. Sacituzumab govitecan is also approved for the treatment of patients with unresectable locally advanced or metastatic hormone-receptor–positive (HR+), and HER2-negative (HER2−) BC who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting. Sacituzumab govitecan was the first Trop-2–directed ADC to demonstrate OS benefit in patients with HR+/HER2− mBC who had received prior endocrine-based therapy and at least 2 chemotherapies. It is now also recommended as a Category 1 preferred treatment for metastatic HR+/HER2− BC by the National Comprehensive Cancer Network.

The results of the TROPiCS-02 study, which led to the FDA approval of sacituzumab govitecan, demonstrated a median OS of 14.4 months with sacituzumab govitecan vs 11.2 months with treatment of physician’s choice (HR, 0.79; 95% CI: 0.65, 0.96; P = 0.02). This represents a 3.2-month improvement in survival and a 21% reduction in the risk for patient death. Before this medicine was approved, there were limited options to offer patients with BC after endocrine-based therapy and chemotherapy.

A third ADC, trastuzumab deruxtecan, targets the HER2 protein, like trastuzumab emtansine, but with a different cytotoxic payload. It consists of trastuzumab linked to deruxtecan, whose cytotoxicity inhibits DNA replication. It is approved for the treatment of HER2+ mBC. Its FDA approval was based on the results of the DESTINY-Breast04  phase 3 clinical trial, which demonstrated that treatment with trastuzumab deruxtecan, when compared with standard-of-care chemotherapy, doubles progression-free survival among patients with mBC that expresses low levels of HER2. The median OS for patients in the HR+ group who received trastuzumab deruxtecan was 23.9 months vs 17.5 months for those who received chemotherapy. In the hormone receptor-negative (HR−) group, the median OS for those who took trastuzumab deruxtecan was 16.6 months vs 10.3 months for those treated with chemotherapy. 

The emergence of ADCs have demonstrated promising advancements in the treatment of BC, particularly in patients with HER2+ or triple-negative disease. ADCs have given new hope to and prolonged life for patients living with pretreated HR+/HER2− mBC. ADCs also have the potential to provide a more effective and less toxic treatment option for patients with BC. However, further research is needed to fully understand their long-term effects and to develop new ADCs that target other types of BC.

The restrictive therapeutic index of chemotherapy has led to the emergence of antibody-drug conjugates (ADCs), medicines that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxic effects of chemotherapy to deliver cytotoxic payloads to cancer cells. This targeted approach can reduce the side effects of chemotherapy and improve the effectiveness of treatment. Several ADCs, including ado-trastuzumab emtansine (Kadcyla), sacituzumab govitecan-hziy (Trodelvy), and fam-trastuzumab deruxtecan-nxki (Enhertu), are currently approved for treating some types of breast cancer (BC).

The ADC trastuzumab emtansine was approved specifically for treating human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in patients who have previously been treated with trastuzumab and a taxane (paclitaxel or docetaxel) and who have already been treated for mBC or have developed tumor recurrence within 6 months of receiving adjuvant therapy. The US Food and Drug Administration (FDA) approval was based on the results of the EMILIA study, a phase 3 clinical trial that compared treatment with trastuzumab emtansine vs capecitabine + lapatinib in participants with HER2+, locally advanced, or metastatic BC. This trial emerged from the need for well-tolerated, HER2-directed therapies for patients with this type of cancer. Trastuzumab emtansine consists of trastuzumab, a mAb that targets HER2 (which is overexpressed in about 20% of BCs), linked to emtansine, a cytotoxic payload that inhibits cell division. The trastuzumab emtansine group had a median overall survival (OS) of 29.9 months vs 25.9 months in the capecitabine + lapatinib group, for a hazard ratio (HR) of 0.75 (95% CI: 0.64, 0.88). 

Another ADC, sacituzumab govitecan, targets the Trop-2 protein, which is overexpressed in BC. This ADC includes a mAb that is linked to SN-38, a cytotoxic payload that inhibits DNA replication. Triple-negative breast cancer (TNBC) is a subtype of BC that does not have receptors for estrogen, progesterone, or HER2—making it more difficult to treat than other forms of BC. Sacituzumab govitecan is used to treat patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease. Sacituzumab govitecan is also approved for the treatment of patients with unresectable locally advanced or metastatic hormone-receptor–positive (HR+), and HER2-negative (HER2−) BC who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting. Sacituzumab govitecan was the first Trop-2–directed ADC to demonstrate OS benefit in patients with HR+/HER2− mBC who had received prior endocrine-based therapy and at least 2 chemotherapies. It is now also recommended as a Category 1 preferred treatment for metastatic HR+/HER2− BC by the National Comprehensive Cancer Network.

The results of the TROPiCS-02 study, which led to the FDA approval of sacituzumab govitecan, demonstrated a median OS of 14.4 months with sacituzumab govitecan vs 11.2 months with treatment of physician’s choice (HR, 0.79; 95% CI: 0.65, 0.96; P = 0.02). This represents a 3.2-month improvement in survival and a 21% reduction in the risk for patient death. Before this medicine was approved, there were limited options to offer patients with BC after endocrine-based therapy and chemotherapy.

A third ADC, trastuzumab deruxtecan, targets the HER2 protein, like trastuzumab emtansine, but with a different cytotoxic payload. It consists of trastuzumab linked to deruxtecan, whose cytotoxicity inhibits DNA replication. It is approved for the treatment of HER2+ mBC. Its FDA approval was based on the results of the DESTINY-Breast04  phase 3 clinical trial, which demonstrated that treatment with trastuzumab deruxtecan, when compared with standard-of-care chemotherapy, doubles progression-free survival among patients with mBC that expresses low levels of HER2. The median OS for patients in the HR+ group who received trastuzumab deruxtecan was 23.9 months vs 17.5 months for those who received chemotherapy. In the hormone receptor-negative (HR−) group, the median OS for those who took trastuzumab deruxtecan was 16.6 months vs 10.3 months for those treated with chemotherapy. 

The emergence of ADCs have demonstrated promising advancements in the treatment of BC, particularly in patients with HER2+ or triple-negative disease. ADCs have given new hope to and prolonged life for patients living with pretreated HR+/HER2− mBC. ADCs also have the potential to provide a more effective and less toxic treatment option for patients with BC. However, further research is needed to fully understand their long-term effects and to develop new ADCs that target other types of BC.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.

To the Editor:

An 85-year-old man with a history of hypertension and chronic kidney disease presented with a localized darkening patch of hair on the left parietal scalp that had progressed over the last 7 years (Figure 1A). He had no prior history of skin cancer. Physical examination revealed the remainder of the hair was gray. There was an irregularly pigmented plaque on the skin underlying the darkened hair measuring 5.0 cm in diameter that was confirmed to be melanoma (Figure 1B). He underwent a staged excision to remove the lesion. The surgical defect was closed via a 5.0×6.0-cm full-thickness skin graft. 

The initial biopsy showed melanoma in situ. However, the final pathology report following the excision revealed an invasive melanoma with a Breslow depth of 1.0 mm (Clark level IV; American Joint Committee on Cancer T1b).¹ Histopathology showed pigment deposition with surrounding deep follicular extension of melanoma (Figure 2).

The patient declined a sentinel lymph node biopsy and agreed to a genetic profile assessment.² The results of the test identified the patient had a low probability of a positive sentinel lymph node and the lowest risk of melanoma recurrence within 5 years. The patient was clear of disease at 12-month follow-up.

Based on a PubMed search of articles indexed for MEDLINE using the terms hair repigmentation and melanoma, there have been 11 other reported cases of hair repigmentation associated with melanoma (Table).^3-13 It initially was suspected that this rare phenomenon primarily existed in the female population, as the first 5 cases were reported solely in females,^3-7 possibly due to the prevalence of androgenetic alopecia in males.¹¹ However, 6 cases of repigmentation associated with melanoma were later reported in males^8-13; our patient represents an additional reported case in a male. It is unknown if there is a higher prevalence of this phenomenon among males or females.

Most previously reported cases of repigmentation were associated with melanoma in situ, lentigo maligna type. Repigmentation also has been reported in malignant melanoma, as documented in our patient, as well as desmoplastic and amelanotic melanoma.^5,6 In every case, the color of the repigmentation was darker than the rest of the patient’s hair; however, the repigmentation color can be different from the patient’s original hair color from their youth.^4,5,11

The exact mechanism responsible for hair repigmentation in the setting of melanoma is unclear. It has been speculated from prior cases that repigmentation may be caused by paracrine stimulation from melanoma cells activating adjacent benign hair follicle melanocytes to produce melanin.^7,14,15 This process likely is due to cytokines or growth factors, such as c-kit ligand.^14,15 Several neural and immune networks and mediators activate the receptor tyrosine kinase KIT, which is thought to play a role in activating melanogenesis within the hair bulb.¹⁴ These signals also could originate from changes in the microenvironment instead of the melanoma cells themselves.⁶ Another possible mechanism is that repigmentation was caused by melanin-producing malignant melanocytes.⁴

Because this phenomenon typically occurs in older patients, the cause of repigmentation also could be related to chronic sun damage, which may result in upregulation of stem cell factor and α-melanocyte–stimulating hormone, as well as other molecules associated with melanogenesis, such as c-KIT receptor and tyrosinase.^15,16 Upregulation of these molecules can lead to an increased number of melanocytes within the hair bulb. In addition, UVA and narrowband UVB have been recognized as major players in melanocyte stimulation. Phototherapy with UVA or narrowband UVB has been used for repigmentation in vitiligo patients.¹⁷

In cases without invasion of hair follicles by malignant cells, repigmentation more likely results from external signals stimulating benign bulbar melanocytes to produce melanin rather than melanoma cell growth extending into the hair bulb.⁶ In these cases, there is an increase in the number of hair bulbar melanocytes with a lack of malignant morphology in the hair bulb.⁸ If the signals are directly from melanoma cells in the hair bulb, it is unknown how the malignant cells upregulated melanogenesis in adjacent benign melanocytes or which specific signals required for normal pigmentation were involved in these repigmentation cases.⁶

Use of medications was ruled out as an underlying cause of the repigmentation in our patient. Drug-related repigmentation of the hair typically is observed in a diffuse generalized pattern. In our case, the repigmentation was localized to the area of the underlying dark patch, and the patient was not on any medications that could cause hair hyperpigmentation. Hyperpigmentation has been associated with acitretin, lenalidomide, corticosteroids, erlotinib, latanoprost, verapamil, tamoxifen, levodopa, thalidomide, PD-1 inhibitors, and tumor necrosis α inhibitors.^18-30 Repigmentation also has been reported after local radiotherapy and herpes zoster infection.^31,32

The underlying melanoma in our patient was removed by staged square excision. Excision was the treatment of choice for most similar reported cases. Radiotherapy was utilized in two different cases.^3,4 In one case, radiotherapy was successfully used to treat melanoma in situ, lentigo maligna type; the patient’s hair grew back to its original color, which suggests that normal hair physiology was restored once melanoma cells were eliminated.³ One reported case demonstrated successful treatment of lentigo maligna type–melanoma with imiquimod cream 5% applied 6 times weekly for 9 months with a positive cosmetic result.⁹ The exact mechanism of imiquimod is not fully understood. Imiquimod induces cytokines to stimulate the production of IFN-α via activation of toll-like receptor 7.³³ There was complete clearing of the lesion as well as the hair pigmentation,⁹ which suggests that the treatment also eliminated deeper cells influencing pigmentation. A case of malignant amelanotic melanoma was successfully treated with anti–PD-1 antibody pembrolizumab (2 mg/kg every 3 weeks), with no recurrence at 12 months. Pembrolizumab acts as an immune checkpoint inhibitor by binding to the PD-1 receptor and allowing the immune system to recognize and attack melanoma cells. After 5 doses of pembrolizumab, the patient was clear of disease and his hair color returned to gray.⁵

In 2022, melanoma was estimated to be the fifth most commonly diagnosed cancer among men and women in the United States.³⁴ Early melanoma detection is a critical factor in achieving positive patient outcomes. Hair repigmentation is a potentially serious phenomenon that warrants a physician visit. Melanoma lesions under the hair may be overlooked because of limited visibility. Physicians must inspect spontaneous hair repigmentation with high suspicion and interpret the change as a possible indirect result of melanoma. Overall, it is important to increase public awareness of regular skin checks and melanoma warning signs.