The Evolving Story of JAK Inhibitors for Treating Alopecia Areata: A Review of Current Progress and Future Directions.

Oral Janus kinase (JAK) inhibitors now have a position as first-line agents for treating advanced alopecia areata. Oral JAK inhibitors are considerably more effective than topical JAK inhibitors, although topical agents may still have a valuable role for specific subgroups of patients. The US FDA approval of baricitinib in 2022 was an important milestone. Numerous JAK inhibitors are now being intensely studied for use in alopecia areata and several additional medications may also become approved in the near future. Accumulating clinical trial data points to a generally good safety profile for JAK inhibitors when used for patients with alopecia areata. However, long-term data pertaining to the safety and efficacy in this patient population are lacking.

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.

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.

Alopecia areata: Part 1: pathogenesis, diagnosis, and prognosis.

OBJECTIVE: To provide family physicians with a background understanding of the epidemiology, pathogenesis, histology, and clinical approach to the diagnosis of alopecia areata (AA). SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the pathogenesis, diagnosis, and prognosis of AA. MAIN MESSAGE: Alopecia areata is a form of autoimmune hair loss with a lifetime prevalence of approximately 2%. A personal or family history of concomitant autoimmune disorders, such as vitiligo or thyroid disease, might be noted in a small subset of patients. Diagnosis can often be made clinically, based on the characteristic nonscarring, circular areas of hair loss, with small "exclamation mark" hairs at the periphery in those with early stages of the condition. The diagnosis of more complex cases or unusual presentations can be facilitated by biopsy and histologic examination. The prognosis varies widely, and poor outcomes are associated with an early age of onset, extensive loss, the ophiasis variant, nail changes, a family history, or comorbid autoimmune disorders. CONCLUSION: Alopecia areata is an autoimmune form of hair loss seen regularly in primary care. Family physicians are well placed to identify AA, characterize the severity of disease, and form an appropriate differential diagnosis. Further, they are able educate their patients about the clinical course of AA, as well as the overall prognosis, depending on the patient subtype.

Alopecia areata: Part 2: treatment.

OBJECTIVE: To provide family physicians with a background understanding of the therapeutic regimens and treatment outcomes for alopecia areata (AA), as well as to help identify those patients for whom dermatologist referral might be required. SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the treatment of AA. MAIN MESSAGE: Alopecia areata is a form of autoimmune hair loss affecting both children and adults. While there is no associated mortality with the disease, morbidity from the psychological effects of hair loss can be devastating. Upon identification of AA and the disease subtype, an appropriate therapeutic regimen can be instituted to help halt hair loss or possibly initiate hair regrowth. First-line treatment involves intralesional triamcinolone with topical steroids or minoxidil or both. Primary care physicians can safely prescribe and institute these treatments. More advanced or refractory cases might require oral immunosuppressants, topical diphenylcyclopropenone, or topical anthralin. Eyelash loss can be treated with prostaglandin analogues. Those with extensive loss might choose camouflaging options or a hair prosthesis. It is important to monitor for psychiatric disorders owing to the profound psychological effects of hair loss. CONCLUSION: Family physicians will encounter many patients experiencing hair loss. Recognition of AA and an understanding of the underlying disease process will allow an appropriate therapeutic regimen to be instituted. More advanced or refractory cases need to be identified, allowing for an appropriate dermatologist referral when necessary.

Platelet-rich fibrin: A review of its role as a new treatment in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a major cause of hair loss resulting from a complex interplay between various genes and hormones with the result being follicular miniaturization and altered hair cycle dynamics. Platelet-rich plasma (PRP) has a well-established role as adjunctive therapy in AGA but there are many limitations of it. In an attempt to overcome the shortcomings of PRP, liquid platelet-rich fibrin (PRF) was developed. AIM: This article critically reviews the protocol for the preparation and clinical outcomes of PRF. PATIENTS/METHODS: The articles published so far in the English language regarding the preparation and clinical outcomes of PRF were reviewed. RESULTS: Among five studies analyzing various centrifugation speeds and centrifugation times, three of the studies favored low-speed centrifugation, whereas two studies did not support this methodology. A horizontal centrifuge may be preferred over a fixed-angle centrifuge for PRF. Five clinical studies on the use of PRF showed a significant effect on AGA. CONCLUSION: At present, there is no consensus regarding the preparation of PRF. Most studies used fixed-angle centrifugation favored low centrifuge speed and less centrifugation time. Larger studies are needed to determine the optimal centrifugation force and time. A horizontal centrifuge may be preferred over a fixed-angle centrifuge due to the higher yield of platelets, and lesser shear trauma to the cells. In addition, larger, well-designed studies are needed to confirm the benefits of PRF over PRP.

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.

Lichen planopilaris: update on pathogenesis and treatment.

Lichen planopilaris (LPP) is considered to be a follicular variant of lichen planus. Clinical variants include classic LPP, frontal fibrosing alopecia, and the Graham-Little-Piccardi-Lassueur syndrome. The pathogenesis of LPP remains to be fully elucidated, but like other cicatricial alopecias involves the irreversible destruction of hair follicle stem cells and loss of a hair follicle's capacity to regenerate itself In the early stages of LPP, patients may have scalp pruritus, burning, tenderness, and increased hair shedding. A scalp biopsy shows a lymphocytic infiltrate involving the isthmus and infundibulum. Apoptotic cells present in the external root sheath and concentric fibrosis surrounds the hair follicle. Treatment is prescribed with the goal to alleviate patient symptoms and to halt the progression of hair loss. Treatment involves use of potent topical corticosteroids and/or intralesional corticosteroids. Options for systemic treatment include anti-inflammatory agents such as hydroxychloroquine, tetracyclines, pioglitazones, and immunosuppressive medications such as cyclosporine, mycophenolate mofetil, or systemic corticosteroids. Hair transplantation may also be an option if the disease has been in clinical remission. The management of LPP can sometimes be challenging and additional research is needed to improve outcomes for patients.

Transversely sectioned biopsies in the diagnosis of end-stage traction alopecia.

The pathogenesis of scarring alopecia in African American women remains poorly understood. Furthermore, the overlapping clinical and histological features present diagnostic challenges. The diagnosis of end stage traction alopecia secondary to traumatic hair styling practices can sometimes present particular challenges. We present a young African American woman with a scarring alopecia. As we describe, a scalp biopsy processed by transverse sections enabled rapid diagnosis and presented advantages over a biopsy processed with vertical sections.

Lichen planopilaris after hair transplantation: report of 17 cases.

BACKGROUND: Lichen planopilaris (LPP) is a type of primary scarring alopecia. The pathogenesis is poorly understood, although traumatic skin injury has been implicated in some cases. OBJECTIVE: To present 17 patients diagnosed with LPP after hair transplant surgery. MATERIALS AND METHODS: A retrospective review of the records of patients referred for evaluation of suboptimal growth after hair transplantation and diagnosed with LPP. Patients' scalps were evaluated using dermoscopy, and scalp biopsies were performed in all patients to confirm the diagnosis of LPP. DISCUSSION: Seventeen patients (15 male, 2 female) were diagnosed with LPP after hair transplant surgery. The timing of disease occurrence was variable--4 to 36 months after hair transplantation. The most common symptom was itching. Perifollicular erythema or perifollicular scale, the classical dermatoscopic signs of LPP,was present in 12 patients (70%). CONCLUSION: These data provide further support for an association between hair transplant surgery and the development of LPP. Traumatic skin injury from recipient site creation may be relevant to the pathogenesis. The incidence of this phenomenon and risk factors remain to be clarified.

The contributions of onset and offset echo delays to auditory spatial perception in human listeners.

In echoic environments, direct sounds dominate perception even when followed by their reflections. As the delay between the direct (lead) source and the reflection (lag) increases, the reflection starts to become localizable. Although this phenomenon, which is part of the precedence effect, is typically studied with brief transients, leading and lagging sounds often overlap in time and are thus composed of three distinct segments: the "superposed" segment, when both sounds are present together, and the "lead-alone" and "lag-alone" segments, when leading and lagging sounds are present alone, respectively. Recently, it was shown that the barn owl (Tyto alba) localizes the lagging sound when the lag-alone segment, not the lead-alone segment, is lengthened. This was unexpected given the prevailing hypothesis that a leading sound may briefly desensitize the auditory system to sounds arriving later. The present study confirms this finding in humans under conditions that minimized the role of the superposed segment in the localization of either source. Just as lengthening the lag-alone segment caused the lagging sound to become more salient, lengthening the lead-alone segment caused the leading sound to become more salient. These results suggest that the neural representations of the lead and lag are independent of one another.

A review of scalp camouflaging agents and prostheses for individuals with hair loss.

Hair loss is a common problem for both men and women and may impact negatively on self-esteem. A variety of medical and surgical treatment options are available depending on the type of alopecia. Many patients also seek the advice of their physicians about options to hide or reduce the appearance of hair loss with hair prostheses (wigs, hairpieces, and extensions) or hair camouflaging agents (hair fibers, powder cakes, lotions, sprays, hair crayons, and scalp tattooing). Herein, we review current methods to hide or reduce the appearance of hair loss and discuss their associated costs, advantages, and disadvantages. Knowledge of products available to cover scalp, eyebrow, and eyelash hair loss may not only better equip clinicians to respond to questions from concerned patients, but may provide additional options to help these patients best cope with their hair loss.

A Global eDelphi Exercise to Identify Core Domains and Domain Items for the Development of a Global Registry of Alopecia Areata Disease Severity and Treatment Safety (GRASS).

Importance: A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. Objective: To generate core domains and domain items for a global network of alopecia areata patient registries. Evidence Review: Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019. Findings: Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented. Conclusions and Relevance: This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.

Iron deficiency and diffuse nonscarring scalp alopecia in women: more pieces to the puzzle.

The relationship between nonscarring scalp alopecia in women and iron deficiency continues to be a subject of debate. We review the literature regarding the relationship between iron deficiency and nonscarring scalp alopecia and describe iron-dependent genes in the hair follicle bulge region that may be affected by iron deficiency. We conclude with a description of our approach to the diagnosis and treatment of nonscarring alopecia in women with low iron stores. Limitations include published studies with small numbers of patients, different study designs, and absence of randomized, controlled treatment protocols. Additional research regarding the potential role of iron during the normal hair cycle is needed, as is a well-designed clinical trial evaluating the effect of iron supplementation in iron-deficient women with nonscarring alopecia.

Mentorship in postgraduate training programmes: views of Canadian programme directors.

OBJECTIVES: Many academic training programmes have developed mentorship programmes for postgraduate doctors in training, but little is known about the factors that influence their establishment. METHODS: Canadian postgraduate training directors were surveyed to determine views on mentorship and factors associated with the establishment of these programmes. RESULTS: A total of 199 of 344 (58%) programme directors completed an online survey. Overall, 65% of respondents reported that their training programmes had a mentorship programme and 40% felt there was a need for more structured mentorship in training programmes. Univariate analysis showed that mentorship programmes were present significantly more often in larger programmes, internal medicine-based training programmes, and in programmes where the acting programme director had either been part of a mentorship programme during his or her own training or felt that mentorship had played an important role in his or her professional development. In adjusting for covariates using a logistic regression analysis, only those factors directly attributable to a programme director's personal mentoring experiences remained significantly associated with having a mentorship programme. Those who felt that mentorship had played a role in their own careers (P = 0.008, odds ratio [OR] = 3.3, 95% confidence interval [CI] 1.7-6.6) or who had been part of a mentorship programme during their own training (P = 0.01, OR = 6.6, 95% CI 1.4-30.1) were more likely to have an active mentorship programme at their institution. CONCLUSIONS: A need for more structured mentorship was identified for many training programmes. Overall, programme directors' previous mentoring experiences were independently associated with having a mentorship programme.

Review of the hair follicle origin hypothesis for basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer treated by the dermatologic surgeon. The discovery that patients with the nevoid BCC syndrome had mutations in the human homologue of the Drosophila patched gene led to a rapid increase in our understanding of the pathogenesis of BCC. It is theorized that altered regulation at multiple steps in the patched signal transduction pathway may contribute to the development of BCC. This pathway also plays an essential role in embryonic hair follicle development and during the hair cycle. Taken together, a considerable body of evidence suggests that at least some BCC may be derived from deregulated patched signaling in hair follicle stem cells. OBJECTIVE: To review evidence of a follicular derivation of BCC and to highlight emerging therapeutic strategies to block deregulated patched signaling in BCC. CONCLUSION: Deregulation of the patched signal transduction pathway is present in the vast majority of human BCCs. Pharmacologic inhibitors of this pathway may offer a therapeutic strategy to block tumor growth. The author has indicated no significant interest with commercial supporters.

A survey of dermatology residency program directors' views on mentorship.

BACKGROUND: It is increasingly recognized that mentoring is important in the career development of resident physicians. The purpose of the study was to determine the views of residency Program Directors on mentorship through a cross sectional survey. METHODS: Respondents included program directors of academic dermatology departments in the United States. RESULTS: Fifty-three of 108 program directors completed an on-line survey (response rate 49%). Eighty-one percent of respondents indicated that mentorship played a 'somewhat' or 'very important' role in their own career development and a similar proportion considered it important for residents to have mentors. Fifty percent of program directors identified a need for more structured mentorship within the residency program. Compared to male program directors, a greater proportion of female program directors stated that mentorship played a very important role in their career development (89% vs. 36%, p=0.007) and a lesser proportion stated that it was important for female dermatology residents to specifically have access to female mentors (11.1% vs. 67.4%, p=0.003). CONCLUSION: Program Directors viewed mentoring as an important resource for their residents' professional development. A need was identified for additional strategies to help residents find mentors.