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The Oxford English Dictionary defines a mentor as a person who acts as guide and adviser to another person. The first reference to mentorship can be found in Greek mythology, when Odysseus asked the goddess Athena to nurture his son. She did this by disguising herself as a human and an old family friend by the name of Mentor. Much of medicine is characterized by definitions and specific criteria, yet mentorship remains less concrete. Failure to understand the qualities and expectations of a mentorship has the potential to greatly jeopardize success and careers and lead to disappointment for those involved in the mentorship (Zerzan et al., 2009). Within dermatology, the mentorship literature has grown rapidly over the last 10 years and further established mentoring as a valuable tool (Donovan, 2009, Kim et al., 2013, Maloney, 2012). The American Academy of Dermatology (AAD) describes a mentor as a “guide, tutor, facilitator, counselor and trusted advisor” (American Academy of Dermatology, 2018, McBurney, 2015). Program directors have found mentoring to be important for the professional development of dermatology residents (Donovan, 2009). Formal long-distance mentoring models have been proposed for those pursuing academic careers (Kim et al., 2013). Approaches to mentoring, traps, and the successes of such a relationship have also been described (McBurney, 2015). Herein, we seek to contribute to the dermatology mentorship literature with a unique viewpoint: that of a successful academic dermatology mentorship. We provide viewpoints from a mentor and mentee on making the most of your mentorship.

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.

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 (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ​ACOXL/​BCL2L11(​BIM) (2q13); ​GARP (​LRRC32) (11q13.5), as well as a third nominally significant region ​SH2B3(​LNK)/​ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.

Thirty-one patients with alopecia areata were administered a structured psychiatric interview (the Diagnostic Interview Schedule; DIS). Overall, 74% had one or more lifetime psychiatric diagnoses. Particularly noteworthy were the high lifetime prevalence rates of major depression (39%) and generalized anxiety disorder (39%). In addition, patients reported increased rates of psychiatric disorders in first-degree relatives: anxiety disorders (58%), affective disorders (35%), and substance use disorders (35%). Patients with patchy alopecia areata were more likely to have a diagnosis of generalized anxiety disorder. No relationships were found between major depression and any variable characterizing alopecia areata history. Possible interrelationships between psychiatric disorders and alopecia areata are discussed. The study suggests that patients with alopecia areata are at increased risk for psychiatric disorders, and calls attention to the need for psychiatric assessment in this population.

Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis). Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis., Highlights • Gene expression analysis of 96 scalp biopsies from patients with alopecia areata (AA) and healthy controls was performed. • Samples from AA patchy, alopecia universalis/totalis and control patients formed distinct clusters by gene expression. • A set of gene expression biomarkers, the Alopecia Areata Disease Activity Index (ALADIN), was formulated. • ALADIN distinguished AA phenotypes and normal controls. • ALADIN may have utility in clinical trials of AA. Alopecia areata is a disease characterized by autoimmune attack of the hair follicle. A complete understanding of the signaling pathways involved in the disease is lacking. Based on gene expression profiling of skin samples from 96 patients and controls, a set of biomarkers, termed the Alopecia Areata Disease Activity Index, or ALADIN, was formulated. ALADIN was able to distinguish samples from patients with patchy disease from samples from patients with the more extensive forms of disease. The usefulness of this biomarker tool is ready to be assessed in clinical trials of therapeutics for alopecia areata.

The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.

13 páginas, 7 figuras, 3 tablas., Alopecia areata (AA) is a genetically determined, immune-mediated disorder of the hair follicle that affects 1%-2% of the U.S. population. It is defined by a spectrum of severity that ranges from patchy localized hair loss on the scalp to the complete absence of hair everywhere on the body. In an effort to define the genetic basis of AA, we performed a genomewide search for linkage in 20 families with AA consisting of 102 affected and 118 unaffected individuals from the United States and Israel. Our analysis revealed evidence of at least four susceptibility loci on chromosomes 6, 10, 16 and 18, by use of several different statistical approaches. Fine-mapping analysis with additional families yielded a maximum multipoint LOD score of 3.93 on chromosome 18, a two-point affected sib pair (ASP) LOD score of 3.11 on chromosome 16, several ASP LOD scores >2.00 on chromosome 6q, and a haplotype-based relative risk LOD of 2.00 on chromosome 6p (in the major histocompatibility complex locus). Our findings confirm previous studies of association of the human leukocyte antigen locus with human AA, as well as the C3H-HeJ mouse model for AA. Interestingly, the major loci on chromosomes 16 and 18 coincide with loci for psoriasis reported elsewhere. These results suggest that these regions may harbor gene(s) involved in a number of different skin and hair disorders., This work was supported in part by grants from the NAAF (to A.M.C. and A.Z.), Israeli Alopecia Areata Fund (to A.Z.), Columbia University Clinical Trials Office Pilot Award (to A.M.-M.), the North American Hair Research Society Mentorship Award (to A.M.-M.), and the National Institutes of Health: National Institute of Arthritis and Musculoskeletal and Skin Diseases grants N01AR02249 (AA Registry [to M.D.]), R03AR050158 (to A.M-M. and J.M.), and R01AR52579 (to A.M.C.) and National Institute of Mental Health grant R01MH44292 (to J.O.).

The hair pluck procedure alters the anatomy of the anagen hair bulb. Hemorrhage can occur in the mesenchymal sheath and breaks at the proximal epithelium, above or around the upper third of the dermal papilla, have been reported. We hypothesized that innervation, as identified with protein gene product 9.5 (PGP 9.5), and expression of the neuropeptide Substance P (SP) within the dermal papilla would also be altered following plucking. We focused on studying SP as this neuropeptide has been associated with several cellular responses, including anagen hair growth in the C57BL/6 mouse model. Four millimeter punch biopsies were obtained from the occipital scalp of two healthy adults. Hair was then plucked and additional biopsies were obtained immediately, and at 1 d, 1 wk, and 1 mo after plucking. Each set was processed for immunohistochemical analyses and in-focus optical sections of the dermal papilla were captured by laser scanning confocal microscopy and later reconstructed into single images. Following injury, SP was expressed in a disorganized pattern below the dermal papilla. There was also a significant reduction in labeled neuronal cells, and SP expression was enhanced within peribulbar blood vessels at 1 d and 1 wk. By 1 mo, peribulbar nerves, vessels, and SP expression were similar to baseline observations. It remains to be ascertained whether PGP 9.5, also known as unbiquitin hydrolase, and SP are involved in the proliferation of new matrix cells in the human scalp hair follicle following injury.

The National Alopecia Areata Registry was awarded as a five-year contract by NIAMS to promote research on the genetic basis of alopecia areata. The registry is Web based and can be accessed online at http://www. AlopeciaAreata Registry.org. Samples of DNA, lymphoblast lines, and sera, as well as epidemiology and quality-of-life data, are being collected from well-characterized individuals, multiplex families, and sib pairs for future research studies and investigators.