A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

Evaluation of ruxolitinib cream 1.5% as an at-home therapy for repigmentation in non-segmental vitiligo.

INTRODUCTION: Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older. AREAS COVERED: The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability. EXPERT OPINION: In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option.  Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.

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.

Evaluating the Cost Burden of Alopecia Areata Treatment: A Comprehensive Review for Dermatologists.

Alopecia areata (AA) is managed with prolonged medical treatments and cosmetic therapies, whose cost can be burdensome. We sought to identify the costs of AA treatment and consolidate the available data for the practicing dermatologist by performing a PubMed search of articles indexed for MEDLINE. Ten studies including approximately 16,000 patients with AA across a range of Oxford Centre for Evidence-Based Medicine Levels of Evidence were included. Studies showed that despite the limited efficacy of many AA therapies, patients incurred substantial expenses to manage their AA.

Depression As a Potential Contributing Factor in Hidradenitis Suppurativa and Associated Racial Gaps.

The etiology of hidradenitis suppurativa (HS)-a chronic, relapsing, inflammatory disorder-is multifactorial, encompassing lifestyle, microbiota, hormonal status, and genetic and environmental factors. These factors propagate the production of deep-seated inflammatory nodules seen in HS through aberrant immune response activation and inflammation. The high prevalence of depression in individuals with HS and its association with systemic inflammation increases the likelihood that depression also may be a contributing etiology to HS. Because depression frequently has been discovered as a concomitant diagnosis in patients with HS, we hypothesize that there is a common susceptibility to depression in patients with HS, which we investigated through a literature search of articles published from 2000 to 2022 involving depression and HS.

Updates on disorders in curly hair.

Hair disorders, including central centrifugal cicatricial alopecia (CCCA), traction alopecia (TA), and acquired trichorrhexis nodosa (ATN), commonly occur in individuals with curly textured hair. Curly textured hair in individuals of African descent has unique properties and can present diagnostic and therapeutic challenges. CCCA has been linked to uterine leiomyoma and type 2 diabetes mellitus, as well as fibroproliferation. TA often presents with a fringe sign and can arise from high-tension hairstyles presumed to be protective. Trichoscopy is useful in establishing a diagnosis; perifollicular halos are more commonly seen than perifollicular erythema or scale in CCCA. In TA, miniaturized follicles, hair casts, and "flambeau sign" can be seen. Hairstyling practices likely contribute to TA and ATN; however, the data are mixed on the role of chemical relaxers and heat styling in CCCA. Unique considerations in the presentation of frontal fibrosing alopecia in curly textured hair have also been published recently. This review provides a comprehensive, up-to-date summary of these disorders with an emphasis on their unique properties, as well as considerations in hair care for curly textured hair.

Acquired Aquagenic Syringeal Keratoderma Following COVID-19 Infection.

Aquagenic syringeal keratoderma (ASK), rare in males, is characterized by the rapid onset of edematous palmar wrinkling with small white papules after brief contact with water or sweat. A 24-year-old atopic male presented with a 2-week subacute history of bilateral palmar edema with whitish-colored papules after exposure to water, 3 months after having had COVID-19 infection treated with a full course of ritonavir-boosted nirmatrelvir (PAXLOVIDTM). He had received 3 COVID-19 vaccines (Pfizer, New York, NY) about 12 months prior. Workup was negative. Initial spontaneous near-resolution 2 months after onset was temporary, with recurrence 1 month later. Treatment with 12% topical aluminum chloride was ineffective. Botulinum toxin injection to both palms led to resolution of symptoms that has been sustained for 7 months. The association between atopy and ASK remains weak. We present a case of new-onset ASK in an adult male 3 months following COVID-19 infection without a history of excessive handwashing. Our patient may have had a predisposition to recurrent ASK due to his history of atopy including atopic dermatitis and food allergy anaphylaxis combined with prior COVID-19 infection. It is possible that ASK is a novel manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) infection or long COVID.

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.

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.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Traction Alopecia.

This Patient Page describes the symptoms, diagnosis, and treatment of traction alopecia.