Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Atypical Dyschromia in Skin of Color.

Dyschromia is a concern for many patients, especially persons of color. Postinflammatory hypopigmentation and depigmentation can affect all skin types; however, it is more apparent in those with darker skin. Some members of the dermatology community may not comprehensively understand the mechanisms of these reactions and the extent of the psychosocial effect they have on persons of color. Skin of color patients experiencing a decrease or loss of pigmentation are left with few treatment options, with no available evidence-based treatment established from a sufficient sample size. Several diseases may present with hypopigmentation and/or depigmentation despite this not being a major criterion for these conditions, including atopic dermatitis, lichen planus, discoid lupus erythematosus, polymorphous light eruption, and scleroderma. Here, we present three cases of atypical dyschromia in skin of color to highlight the underlying hypo- and depigmentation that may present with active disease and persist despite appropriate treatment.  Practice Points: 1. These cases foreground the potential for a range of dermatologic conditions to result in atypical pigment changes in persons of color. 2. Postinflammatory hypopigmentation or depigmentation may persist in skin of color despite the regression of active disease.J Drugs Dermatol. 2024;23(2):100-102.     doi:10.36849/JDD.7683.

Outcomes for Psoriasis by Self-Identified Racial Groups in Ixekizumab Clinical Trials: A Pooled Analysis.

BACKGROUND: Biologics have shown promising outcomes in psoriasis clinical trials. However, there is a paucity of data exploring the potential differences in outcomes between self-identified racial groups. OBJECTIVE: To evaluate treatment response to ixekizumab in patients with psoriasis across different self-identified racial subgroups. METHODS: This study analyzed pooled data from 5 clinical studies (UNCOVER-1, UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) with patients of different self-identified racial subgroups, who were treated with an on-label dose of ixekizumab for psoriasis through 12 weeks. Treatment response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and static Physician’s Global Assessment response rates. Patient Global Assessment of Disease Severity, Itch Numeric Rating Scale, Skin Pain Visual Analog Scale, and Dermatology Life Quality Index were used to evaluate the patient-reported outcomes (PROs) and impact on quality of life (QoL). RESULTS: A total of 1825 ixekizumab-treated patients from 5 pooled studies were included. Consistent with the clinical outcomes from the overall population, all self-identified racial groups showed rapid improvement in PASI through Week 12, although the response was somewhat slower in American Indian/Alaska Native patients. Differences in PROs and QoL assessments were observed among racial groups, especially in patients who identified as Black/African American and American Indian/Alaska Native. CONCLUSION: Ixekizumab is effective through 12 weeks of treatment for psoriasis across different self-identified racial groups. Sample sizes for some racial groups were small (N≤12), therefore, further research is required to understand potential differences in psoriasis treatment with ixekizumab between various racial groups.J Drugs Dermatol. 2024;23(2):17-22.  doi:10.36849/JDD.7672.

Special Considerations of Atopic Dermatitis in Skin of Color.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with heterogeneous presentations and prevalence across different skin tones. In this chapter, AD is explored through the lens of racial and ethnic diversity, emphasizing the special considerations among patients with skin of color (SOC). Specific ethnic groups may exhibit unique AD phenotypes, and these differences pose unique diagnostic and management challenges, especially given the disproportionate impact of AD in African American and Asian populations due to environmental exposures and social factors (i.e., decreased access to healthcare resources). Addressing these social disparities, increasing representation in medical education and the clinical space, as well as ongoing research can help better serve this patient population.

Topical Minoxidil Adherence in Patients With Alopecia.

BACKGROUND: Non-adherence to topical minoxidil in alopecia patients is a barrier to efficacy. Understanding patient factors associated with adherence and non-adherence may provide actionable targets to improve adherence and outcomes. METHODS: Ninety-nine alopecia patients at an outpatient university dermatology specialty clinic completed a survey assessing demographics and aspects of treatment adherence. Patients currently using minoxidil additionally completed a survey grading their level of adherence. A two-sample t-test was used to compare the average age between adherent and non-adherent groups. Differences in demographics and patient factors by adherence level were evaluated using the 2-tailed χ2 test and Fisher's exact test. RESULTS: Adherent patients had been using topical minoxidil for a median of 24 months when surveyed; non-adherent patients used the medication for a median of 3.5 months prior to discontinuation. A larger portion of non-adherent patients used minoxidil for fewer than 3 months (35%) compared to adherent patients (3%), P<.001. The most common reason non-adherent patients discontinued therapy was no improvement (50%). DISCUSSION/CONCLUSION: Non-adherent patients were less likely to use topical minoxidil for at least 3 months and often cited lack of improvement as a reason for discontinuing. Patient education and intervention prior to the 3-month mark may help improve adherence. J Drugs Dermatol. 2023;22(3): doi:10.36849/JDD.6639.

Variant PADI3 in Central Centrifugal Cicatricial Alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. We sought to determine whether there exists a genetic basis of CCCA and, if so, what it is. METHODS: We used exome sequencing in a group of women with alopecia (discovery set), compared the results with those in a public repository, and applied other filtering criteria to identify candidate genes. We then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modeling, immunofluorescence staining, immunoblotting, and an enzymatic assay to evaluate the consequences of potential etiologic mutations. We used a replication set that consisted of women with CCCA to confirm the data obtained with the discovery set. RESULTS: In the discovery set, which included 16 patients, we identified one splice site and three heterozygous missense mutations in PADI3 in 5 patients (31%). (The approximate prevalence of the disease is up to 5.6%.) PADI3 encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post-translationally modifies other proteins that are essential to hair-shaft formation. All three CCCA-associated missense mutations in PADI3 affect highly conserved residues and are predicted to be pathogenic; protein modeling suggests that they result in protein misfolding. These mutations were found to result in reduced PADI3 expression, abnormal intracellular localization of the protein, and decreased enzymatic activity - findings that support their pathogenicity. Immunofluorescence staining showed decreased expression of PADI3 in biopsy samples of scalp skin obtained from patients with CCCA. We then directly sequenced PADI3 in an additional 42 patients (replication set) and observed genetic variants in 9 of them. A post hoc analysis of the combined data sets showed that the prevalence of PADI3 mutation was higher among patients with CCCA than in a control cohort of women of African ancestry (P = 0.002 by the chi-square test; P = 0.006 by Fisher's exact test; and after adjustment for relatedness of persons, P = 0.03 and P = 0.04, respectively). CONCLUSIONS: Mutations in PADI3, which encodes a protein that is essential to proper hair-shaft formation, were associated with CCCA. (Funded by the Ram Family Foundation and others.).

Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata.

BACKGROUND: Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. OBJECTIVE: To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. RESULTS: A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. LIMITATIONS: These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. CONCLUSIONS: Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Evolving Concepts in Psoriasis: Special Considerations for Patients With Skin of Color, Skin Barrier Dysfunction, and the Role of Adjunctive Skin Care.

BACKGROUND: Despite considerable advances in our understanding of the pathogenesis and treatment of psoriasis, data pertaining to racial/ethnic variations, effects on barrier function, and the potential role of adjunctive skin care are relatively limited. Knowledge gaps in the clinical presentation, quality-of-life impact, and approach to treating psoriasis in patients with skin color contribute to disparities in care. In addition, small studies suggest that using skincare products can reduce psoriasis symptoms, improve barrier function, and result in higher patient satisfaction, yet patients with psoriasis may underuse skincare products. This manuscript seeks to offer insights into these knowledge gaps and their potential treatment implications. METHODS: A structured literature search followed by a panel discussion and an online review process explored best clinical practices in treating psoriasis patients with skin of color and providing expert guidance for skincare use, including gentle cleansers and moisturizers. RESULTS: Racial/ethnic differences in genetic factors, clinical presentation, and disease burden in psoriasis have been reported. Underrecognition of these differences contributes to racial/ethnic health disparities for psoriasis patients in the US. Several studies have shown a greater quality-of-life impact with psoriasis among patients with skin of color. Although the published data are limited, some studies have identified differences in skin barrier properties and suggest a role for adjunctive skin care in the management of psoriasis. CONCLUSION: Further study is needed to understand racial/ethnic population variations in psoriasis and develop strategies to reduce disparities in care. Addressing alterations in skin barrier function observed in psoriasis may help to improve treatment outcomes and patient satisfaction. J Drugs Dermatol. 2022;21(10):1054-1060. doi:10.36849/JDD.7090.

The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata.

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

Recurrent Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Induced by Levamisole-Adulterated Cocaine.

ABSTRACT: Levamisole, an anthelmintic and immunomodulatory drug, was withdrawn from the US market in 1999 due to adverse effects, including agranulocytosis and vasculitis. In recent years, levamisole has been used as a common cocaine adulterant, and its use has led to an autoimmune syndrome characterized by an antineutrophil cytoplasmic antibody-associated vasculitis presenting with necrotic retiform purpura on the face and extremities. We present a case of recurrent levamisole-induced vasculitis initially misdiagnosed as systemic lupus erythematosus to highlight this easily misdiagnosed entity and to demonstrate re-exposure leading to recurrent vasculitis with more extensive clinical manifestations.

A proposed mechanism for central centrifugal cicatricial alopecia.

Central centrifugal cicatricial alopecia (CCCA) has an unknown mechanism. Analyzing other scarring diseases (lichen planopilaris, fibrotic kidney disease and scleroderma) may help to clarify the mechanism of scarring in CCCA. These diseases were chosen for comparison due to either their location of disease (skin or scalp specifically), or prominence in patients of African descent. Genetics, possible triggers, an autoimmune lymphocytic response, and epithelial to mesenchymal transition are potentially involved. Possible common pathways in scarring diseases and a better understanding of the CCCA mechanism will lead to further research into the pathogenesis and potential treatments of CCCA.

Sunscreen and frontal fibrosing alopecia: A review.

Frontal fibrosing alopecia (FFA) is a cicatricial alopecia of unknown etiology. The incidence of FFA appears to be increasing with time, leading to suspicion of a possible environmental trigger. Observational studies have reported a positive correlation between facial sunscreen use and FFA. This finding raises the question of whether sunscreen use plays a role in disease development. In this article, we review the available literature on the association of sunscreen with FFA. There is insufficient evidence to establish a direct causal relationship between sunscreen and FFA. Further studies are required to better characterize the role of sunscreen and the environment in the pathogenesis of this unique disease.

The Alopecia Areata Consensus of Experts (ACE) study: Results of an international expert opinion on treatments for alopecia areata.

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.

Intralesional Triamcinolone Acetonide in the Treatment of Traction Alopecia

Traction alopecia (TA) is a form of hair loss caused by continuous and prolonged tension to the hair, most commonly seen in Black/African American women and children who wear hairstyles that pull excessively at the frontotemporal hairline. Dermatologists have recommended the use of intralesional triamcinolone acetonide injections (ILK) to decrease the inflammatory process, however, evidence-based proof is lacking in the literature. In this case series, we evaluate the effectiveness and safety of ILK in the TA management of 6 African American women. A retrospective chart review was done of patients with a diagnosis of TA, who were treated with ILK at an academic dermatology clinic, yielding 6 patients. Management of TA was assessed by comparing the photographs for changes in hair density along the frontotemporal hairline. ILK with a concentration of 5 mg/mL, was administered in areas of low hair density along the frontotemporal hairline at 6 to 8-week intervals, for 3 successive visits. All subjects demonstrated visible increase in hair density along the frontotemporal hairline following their first or second treatment, and no severe adverse effects were observed or reported. The use of ILK is currently an effective and safe method of treating TA, particularly in the early to mid-stages. Common adverse effects are pain, and subsequent transient atrophy at the injection site. The transient atrophy is not an indication to stop treatment. Avoidance of treating dented areas is sufficient to allow it to revert. Patient education is pivotal in the prevention and management of TA. It is imperative that dermatologists caution against grooming practices that exert tension on the hairline. J Drugs Dermatol. 2020;19(2)128-130. doi:10.36849/JDD.2020.4635

Publication rates on the topic of racial and ethnic diversity in dermatology versus other specialties.

BACKGROUND: The population of the U.S. is becoming more diverse every year. The field of dermatology is not following the same trend. OBJECTIVE: To assess the promotion of diversity in the field of dermatology by analyzing publications focused on diversity, compared to other specialties. METHODS: The PubMed database was systematically searched to identify publications focused on diversity from January 2008 to July 2019. The search criteria were as follows: dermatology/radiology/ophthalmology/ anesthesiology/orthopedic surgery/family medicine/ internal medicine/general surgery AND diversity/ diverse/racial/race/ethnic/ethnicity/cultural/culture/competency/competence. Comparisons were made using single-factor ANOVA and two-group t-tests. A qualitative analysis was performed for publications in the field of dermatology. RESULTS: From January 2016 to July 2019, there were 25 publications focused on diversity in dermatology (Mean=6.25, SD=2.06), compared to 6 in radiology (Mean=1.50, SD=1.29, P=0.01), two in ophthalmology (Mean=0.50, SD=0.58, P=0.01), two in anesthesiology (Mean=0.50, SD=1.00, P=0.01), 12 in orthopedic surgery (Mean=3.00, SD=1.41, P=0.04), 23 in family medicine (Mean=5.75, SD=2.22, P=0.75), 9 in internal medicine (Mean=2.25, SD=1.71, P=0.02), and 7 in general surgery (Mean=1.75, SD=0.50, P=0.02). CONCLUSIONS: Although the field of dermatology has suffered from a lack of racial/ethnic diversity, efforts to promote diversity via increased publications in the last four years have been stronger in dermatology compared to many other fields.

Hypopigmented Macules as Manifestation of Lichen Planus and Lichen Planopilaris.

Lichen planus (LP) is an idiopathic inflammatory disease of the skin, hair, nails, and mucous membranes. Classic cutaneous LP is characterized by violaceous flat-topped papules that typically favor the extremities. LP on the scalp, otherwise known as lichen planopilaris, classically presents with scarring alopecia, perifollicular erythema and follicular prominence. Although LP pigmentosus presents primarily as hyperpigmentation, there is only one previous report of hypopigmented LP. In this report, the authors report 2 cases of LP that presented primarily as hypopigmented macules in 2 African American men. The first patient presented with hypopigmented macules on face and scalp as well as trunk and extremities. The second patient presented with hypopigmented macules on scalp with associated alopecia. Histopathological examination from both patients showed features of LP. The authors propose a new variant of LP that presents acutely as hypopigmented lesions.