Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

AbstractAlopecia 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

Genome-Wide Meta-Analysis in Alopecia Areata Resolves HLA Associations and Reveals Two New Susceptibility Loci

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in 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 MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed 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, TGFß/Tregs and JAK kinase signaling, and support the causal role of aberrant immune processes in AA

Evidence-Based Management of Hand Eczema

Hand eczema is a common skin disease with a wide variation in morphology and a complex etiology based on endogenous and exogenous factors.The diagnosis of hand eczema is based on patient history, exposure assessment, physical examination, and the results of patch testing. Management of hand eczema starts with education of the patient on the etiology of the disease, and the needed changes in behavior regarding skin care and preventive measures, and avoidance of relevant exposure factors. In many cases, medical treatment is needed for successful management of the disease; use of medication can only be successful with proper education and avoidance of relevant exposure

Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

YesAlopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.Canadian Institutes of Health Researches (Funding Reference Number: 134214 and 136945)

Wounding, mortality and mane morphology in African lions, Panthera leo

A protective role for the lion's mane has long been assumed but this assumption has never been tested. We compared patterns of injury, mane development and adult mane morphology in a population of African lions and found no compelling evidence that the mane conferred effective protection against wounding. The mane area was not a specific target of attacks, and injuries to the mane area were not associated with higher mortality than other injuries. Regions of the mane that were most frequently attacked did not show earlier onset of mane growth in subadult males or longer/darker mane hair in adult males. Adult males appeared to be wounded less frequently on the mane area than predicted by surface area, but it is unclear whether this trend was only caused by observer bias from decreased visibility. We conclude that, although the mane may have conferred protection during the early evolution of the trait, protection appears to be secondary to the strong sexually selected advantages of the mane as a condition-dependent ornament

Fibrosing alopecia in a pattern distribution

Fibrosing alopecia in a pattern distribution (FAPD) is a newly recognized form of scarring alopecia sharing characteristics of both androgenetic alopecia (AGA) and lichen planopilaris. The existing literature on FAPD and current understanding of the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this disease are reviewed. PubMed searches were performed to identify all articles discussing FAPD. The references of articles were used to identify additional articles. A total of 15 articles were found describing FAPD in a total of 188 patients (164 women and 24 men; average age, 53.8). FAPD affects the androgen-dependent scalp and is typically associated with hair follicle miniaturization. The scalp affected by FAPD shows features of both lichen planopilaris and AGA, and FAPD may possibly represent an exaggerated inflammatory response to damaged hair follicles, triggered by AGA. Physical examination and trichoscopic evidence of follicular inflammation and, occasionally, fibrosis are important to identify the condition, and a dermoscopy-guided biopsy can confirm the diagnosis. Unless recognized, clinicians may misdiagnose FAPD as AGA associated with seborrheic dermatitis. Data on treatment modalities are limited; however, based on pathogenesis, combined therapy with anti-inflammatory and hair growth–promoting agents is warranted