Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction.

Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting ß-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.

M1 polarization of macrophages promotes stress-induced hair loss via interleukin-18 and interleukin-1ß.

Stress-induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress-induced hair loss was related to an imbalanced immune microenvironment. Screening the skin-infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress-induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress-induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in-vivo and in-vitro studies confirm that NE can induce macrophage polarization toward M1 through the ß-adrenergic receptor, Adrb2. Transcriptome, enzyme-linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase-1 inflammasome signaling and its downstream effector interleukin 18 (IL-18) and interleukin 1 beta (IL-1ß) were significantly upregulated in the NE-treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase-1, IL-18, and IL-1ß. Indeed, IL-18 and IL-1ß treatments lead to apoptosis of HFSCs. More importantly, blocking IL-18 and IL-1ß signals reversed HFSCs depletion in skin organoid models and attenuated stress-induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)-endocrine (NE)-immune (M1 macrophages) axis in stress-induced hair shedding and suggestes that IL-18 or IL-1ß may be promising therapeutic targets.

Disturbance of Immune Microenvironment in Androgenetic Alopecia through Spatial Transcriptomics.

Androgenetic alopecia (AGA) is characterized by microinflammation and abnormal immune responses, particularly in the upper segment of hair follicles (HFs). However, the precise patterns of immune dysregulation remain unclear, partly due to limitations in current analysis techniques to preserve tissue architecture. The infundibulum, a major part of the upper segment of HFs, is associated with significant clusters of immune cells. In this study, we investigated immune cells around the infundibulum, referred to as peri-infundibular immune infiltration (PII). We employed spatial transcriptome profiling, a high-throughput analysis technology, to investigate the immunological disruptions within the PII region. Our comprehensive analysis included an evaluation of overall immune infiltrates, gene set enrichment analysis (GSEA), cellular deconvolution, differential expression analysis, over-representation analysis, protein-protein interaction (PPI) networks, and upstream regulator analysis to identify cell types and molecular dysregulation in immune cells. Our results demonstrated significant differences in immune signatures between the PII of AGA patients (PII-A) and the PII of control donors (PII-C). Specifically, PII-A exhibited an enrichment of CD4+ helper T cells, distinct immune response patterns, and a bias toward a T helper (Th) 2 response. Immunohistochemistry revealed disruptions in T cell subpopulations, with more CD4+ T cells displaying an elevated Th2 response and a reduced Th1-cytotoxic response compared to PII-C. These findings reveal the unique immune landscapes of PII-A and PII-C, suggesting potential for the development of innovative treatment approaches.

CCL13 is upregulated in alopecia areata lesions and is correlated with disease severity.

Alopecia areata (AA) is a multi-factors disease characterized by non-scarring hair loss. AA could be classified into three main clinical phenotypes including patchy type AA (AAP), alopecia totalis (AT) and alopecia universalis (AU) based on the severity and areas of hair loss. Recent studies suggested immunological factor was critical in AA, but the precise aetiology and pathogenesis of AA still need exploration. In the work, we screened two gene expression profiles (GSE45512 and GSE68801) from Gene Expression Omnibus (GEO). Based on the two data sets, 10 upregulated genes and 107 downregulated genes in AA skin biopsies were identified. CCL13, as one of the remarkably upregulated genes, was found to have potential biological functions in aberrant immune response of AA according to the GO and KEGG analyses. The PPI network showed CCL13 was associated with multiple immune-related genes. The expression of CCL13 was increased depending on the severity of disease in AA patients. Cytotoxic lymphocytes, T cells and myeloid dendritic cells accumulated remarkably in scalp tissue depending on the severity of AA, and CCL13 was significantly correlated to cytotoxic lymphocytes, T cells and myeloid dendritic cells in AA patients. Our RT-PCR and ELISA results found CCL13 was upregulated in skin biopsy and serum of AA patients, and the immunohistochemistry (IHC) detection showed CCL13 was expressed by both the hair follicle epithelium and infiltrating immune cells. In conclusion, the upregulated of CCL13 and subsequent immune cell infiltration was related to AA, which could be a promising target for diagnosis and therapy in AA patients.

Cutaneous, systemic features and laboratory characteristics of late- versus adult-onset systemic lupus erythematosus in 1006 Thai patients.

BACKGROUND: Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. OBJECTIVE: To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients. METHODS: Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. RESULTS: Of 1006 SLE patients, 740 and 226 had adult- (15-50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively (p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. CONCLUSIONS: Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.

Histopathological and immunohistochemical features of facial papules in frontal fibrosing alopecia.

BACKGROUND: Facial papules (FPs) are considered to be created by the inflammatory process, which involves facial vellus hairs, in frontal fibrosing alopecia. AIM: To demonstrate the histopathological features of FPs and the composition of the inflammatory infiltrate. METHODS: In total, 18 patients with FPs were enrolled in the study after histopathological confirmation of lichen planopilaris. Histopathological evaluation of the specimens was performed by two dermatopathologists. The samples were immunostained with CD4, CD8 and CD123 monoclonal antibodies, and the percentage and proportion of cells stained with these markers were investigated. RESULTS: A follicular lichenoid reaction and perifollicular fibrosis were present in all cases. Vellus hairs were detected in 83.3% of biopsy specimens (15 cases), all of which were involved by the inflammation. The majority of the follicles (72%) revealed follicular plugs. Reduction and destruction of elastic fibres were visible in the perifollicular (adventitial) and the papillary dermis (100% and 78% of specimens, respectively). Prominent sebaceous glands and dilated ducts were detected in 78% and 72% of samples, respectively. CD4-positive T cells formed 67.72% and CD8-positive T cells 32.28% of the infiltrate, and the mean CD4/CD8 ratio was 2.48. In 13 (72.2%) biopsy specimens < 10% of the infiltrate was positive for CD123 marker. CONCLUSIONS: Perifollicular inflammation, fibrosis and elastic-fibre destruction were constant histopathological features of FPs; furthermore, prominent sebaceous glands were present in the majority of samples. We also observed a CD4-positive predominance in the infiltrate.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Pathomechanisms of immune-mediated alopecia.

The hair follicle (HF) is a complex mini-organ that constantly undergoes dynamic cycles of growth and regression throughout life. While proper progression of the hair cycle requires homeostatic interplay between the HF and its immune microenvironment, specific parts of the HF, such as the bulge throughout the hair cycle and the bulb in the anagen phase, maintain relative immune privilege (IP). When this IP collapses, inflammatory infiltrates that aggregate around the bulge and bulb launch an immune attack on the HF, resulting in hair loss or alopecia. Alopecia areata (AA) and primary cicatricial alopecia (PCA) are two common forms of immune-mediated alopecias, and recent advancements in understanding their disease mechanisms have accelerated the discovery of novel treatments for immune-mediated alopecias, specifically AA. In this review, we highlight the pathomechanisms involved in both AA and CA in hopes that a deeper understanding of their underlying disease pathogenesis will encourage the development of more effective treatments that can target distinct disease pathways with greater specificity while minimizing adverse effects.

Clinicopathologic and immunophenotypic characterization of lichen planopilaris and central centrifugal cicatricial alopecia: A comparative study of 51 cases.

BACKGROUND: The purpose of the study was to compare the histopathologic and immunophenotypic features of central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP) to better characterize and differentiate these two clinical entities. CCCA remains an ill-defined and still-unsettled histologic entity and many hair loss experts regard CCCA to be histologically indistinguishable from LPP. Given the overlapping histologic features of these two lymphocyte-predominant cicatricial alopecias, and the lack of consensus regarding the significance of proposed distinctions, dermatopathologists face difficulty in providing clinicians and patients certainty with a definitive diagnosis of CCCA vs LPP. METHODS: We performed a retrospective review of 51 scalp biopsies of patients with either the clinical diagnosis of CCCA (27 cases) or LPP (24 cases). Clinical information, histologic features of hematoxylin-eosin-stained sections, and a panel of immunohistochemical markers were evaluated on scalp biopsies. Tested parameters were quantified, and statistical analysis was performed. RESULTS: Our study found no differences on either histologic assessment or immunophenotypic characterization between cases of classic LPP and CCCA. CONCLUSION: The conclusion of this study is that the inflammatory infiltrates in CCCA and LPP are not only histologically similar but also immunophenotypically indistinguishable.

Regulatory T Cells and Their Association with Serum Markers and Symptoms in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

PURPOSE: Impairment in number and functions of regulatory T cells (Treg) has been found to be associated with many autoimmune diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study was conducted to identify and compare Treg by flow cytometry using two different staining approaches. METHODS: Treg were identified by using CD4+CD25+high and CD4+CD25+CD127dim staining approaches in SLE and RA patients and healthy controls. Association of both identified Treg levels with various serum markers and clinical presentation was also examined. RESULTS: Blood CD4+CD25+CD127dim cells levels were 11.4+3.57 %, 9.76+2.37 % and 6.95+1.16 %; while CD4+CD25+high cells were 1.46+1.09 %, 0.95+0.59 % and 1.87+1.14 % in SLE patients, RA patients and healthy controls respectively. Number of CD4+CD25+CD127dim cells was higher than CD4+CD25+high cells in blood samples of all three study groups. Levels of CD4+CD25+CD127dim cells were significantly higher in SLE and RA patients, compared to healthy controls, but this difference was not observed for CD4+CD25+high Treg. CD4+CD25+high levels showed significant correlation with serum C4, IFN-γ and IL-10 levels in healthy subjects and with C4 levels and fever in SLE patients. CD4+CD25+CD127dim levels showed significant association with alopecia and oral ulcers in SLE patients only, but no correlation with measured serum markers. CONCLUSION: Results suggest that both staining approaches detect Treg differently and also that Treg play different role in pathogenesis of SLE and RA.

Comparison of the Treatment Outcome of Oral Tofacitinib with Other Conventional Therapies in Refractory Alopecia Totalis and Universalis: A Retrospective Study.

Treatment of alopecia totalis and alopecia universalis is often challenging and unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The aim of this study is to compare the efficacy and tolerability of oral tofacitinib and conventional modalities for treating refractory alopecia totalis/universalis. A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional oral treatment (steroid ± cyclosporine), and 30 treated with diphenylcyclopropenone) were included in the study. The patients' medical records were reviewed retrospectively. After 6 months, 44.4% of patients in the tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in the diphenylcyclopropenone group achieved 50% improvements in the Severity of Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group, 73.1% in the conventional oral treatment group, and 10% in the diphenylcyclopropenone group experienced adverse drug reactions. In conclusion, oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and more tolerable than conventional oral treatment after 6 months of treatment.

Increased risk of severe course of pemphigus in patients with pemphigus-associated alopecia: a prospective observational study.

BACKGROUND: Pemphigus-associated alopecia is considered rare, and has not been studied in detail. AIM: To evaluate the clinical and immunological characteristics of patients with pemphigus-associated alopecia. METHODS: This prospective observational study included 80 consecutive patients with histopathologically and immunopathologically confirmed pemphigus, of whom 11 (13.8%) were found to have pemphigus-associated alopecia. Alopecia was observed in 11/52 patients with pemphigus and scalp involvement: [0/28 (35.7%) with pemphigus vulgaris and 1/24 (4.2%) with pemphigus foliaceus. The clinical and immunological characteristics of these patients were analysed. RESULTS: Patients with pemphigus-associated alopecia had a significantly higher Pemphigus Disease Area Index total activity score compared with patients who had no pemphigus-associated alopecia (21.8 ± 18.6 and 11.0 ± 20.5, respectively; P = 0.02). Mean serum anti-desmoglein (Dsg)1 antibody concentration was 141.8 ± 66.9 U/mL and 60.0 ± 52.6 U/mL, respectively (P = 0.03), and mean serum anti-Dsg3 concentration was 126.6 ± 36.7 U/mL and 67.4 ± 52.5 U/mL, respectively (P = 0.03). The values for achieving serological remission were 10% and 70%, respectively (P = 0.02). CONCLUSIONS: Pemphigus-associated alopecia is a marker of severe disease and a treatment-resistant disease course.

An update of the pathogenesis of frontal fibrosing alopecia: What does the current evidence tell us?

Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia with a complicated pathogenesis yet to be fully understood. FFA appears to be increasing in incidence worldwide, especially in the last decade. In order to consider current treatment options, we reviewed current evidence for its pathogenesis comprising immune-mediated, genetic, hormonal and environmental factors. Th1-mediated inflammation with collapse of hair follicle immune privilege and bulge epithelial stem cell destruction, peroxisome proliferator-activated receptor gamma (PPAR-γ) depletion and epithelial-mesenchymal transition are key events leading to permanent hair follicle destruction in FFA. Although the vast majority of cases are sporadic, familial reports of FFA implicate genetic or epigenetic mechanisms in its pathogenesis. The frequent onset of FFA in post-menopausal women, similar patterning and co-existence with female pattern hair loss, together with a reportedly good response to 5α-reductase inhibitors suggest a role for sex steroid hormones. The reported increasing incidence invites speculation for, yet unproven, environmental triggers such as sun exposure and topical allergens. More robust research into this unique entity is required to help understand the complexity of the pathogenesis of FFA in order to find satisfactory therapeutic targets for this often distressing condition.

Autoimmunity in lichen planopilaris patients.

Lichen planopilaris (LPP) is a rare, scarring form of alopecia with lymphocytic pattern. Due to the destruction of epithelial hair follicle stem cells in the bulge, it represents an irreversible condition. Antinuclear antibodies have been used for decades as diagnostic biomarkers of several rheumatological diseases. AIM: The aim of study was to determine the frequency of anti-nuclear antibodies positivity and subsequently analyze the presence of specific antibodies in LPP patients. MATERIALS AND METHODS: 57 patients (aged 28-79, female 96%) were included in the study. Patients with LPP were treated in Department of Dermatology of University Hospital in Cracow, Poland and were identified on individual record review. Antinuclear antibodies were detected using indirect immunofluorescence on HEp-2 cells and immunoblot test. RESULTS: Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common. CONCLUSIONS: Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common.

A Novel Xenogeneic Graft-Versus-Host Disease Model for Investigating the Pathological Role of Human CD4+ or CD8+ T Cells Using Immunodeficient NOG Mice.

Graft-versus-host disease (GVHD) is a major complication of allogenic bone marrow transplantation and involves the infiltration of donor CD4+ and/or CD8+ T cells into various organs of the recipient. The pathological role of human CD4+ and CD8+ T cells in GVHD remains controversial. In this study, we established two novel xenogeneic (xeno)-GVHD models. Human CD4+ or CD8+ T cells were purified from peripheral blood and were transplanted into immunodeficient NOD/Shi-scid IL2rgnull (NOG) mice. Human CD8+ T cells did not induce major GVHD symptoms in conventional NOG mice. However, CD8+ T cells immediately proliferated and induced severe GVHD when transferred into NOG mice together with at least 0.5 × 106 CD4+ T cells or into NOG human interleukin (IL)-2 transgenic mice. Human CD4+ T cell-transplanted NOG mice developed skin inflammations including alopecia, epidermal hyperplasia, and neutrophilia. Pathogenic T helper (Th)17 cells accumulated in the skin of CD4+ T cell-transplanted NOG mice. Further, an anti-human IL-17 antibody (secukinumab) significantly suppressed these skin pathologies. These results indicate that pathogenic human Th17 cells induce cutaneous GVHD via IL-17-dependent pathways. This study provides fundamental insights into the pathogenesis of xeno-GVHD, and these humanized mouse models may be useful as preclinical tools for the prevention of GVHD.

CD80CD86 deficiency disrupts regulatory CD4+FoxP3+T cell homoeostasis and induces autoimmune-like alopecia.

Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86-/- ) mice. Incidence and severity of alopecia were analysed in 58 B6.CD80CD86-/- mice using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR and CD25 inhibition test. Both male and female B6.CD80CD86-/- mice showed almost 100% incidence of hair loss at 40 weeks of age. Moreover, CD4+FoxP3+Treg (Treg) cell population in B6.CD80CD86-/- mice was significantly lower than in B6 mice, which presumably underlined autoimmune reaction. Histologically, B6.CD80CD86-/- mice showed CD4+ and CD8+ T-cell infiltration around terminal follicle region and exhibited hair follicle destruction in the anagen or catagen stage. Negative correlation between the number of CD4+FoxP3+ Tregs and ALA was confirmed by the CD25 depletion test in B6 mice, as follicle destruction was similar to that observed in B6.CD80CD86-/- animals. CD80CD86 deficiency disrupted CD4+FoxP3+ Treg homoeostasis and prompted the development of ALA. We demonstrated that B6.CD80CD86-/- mice might have several advantages as an ALA model, because they exhibited high incidence of disease phenotype and epipathogenesis similar to that observed in human AA.

A spontaneous deletion within the desmoglein 3 extracellular domain of mice results in hypomorphic protein expression, immunodeficiency, and a wasting disease phenotype.

Desmoglein 3 is a transmembrane component of desmosome complexes that mediate epidermal cell-to-cell adhesion and tissue integrity. Antibody blockade of desmoglein 3 function in pemphigus vulgaris patients leads to skin blistering (acantholysis) and oral mucosa lesions. Desmoglein 3 deficiency in mice leads to a phenotype characterized by cyclic alopecia in addition to the dramatic skin and mucocutaneous acantholysis observed in pemphigus patients. In this study, mice that developed an overt squeaky (sqk) phenotype were identified with obstructed airways, cyclic hair loss, and severe immunodeficiency subsequent to the development of oral lesions and malnutrition. Single-nucleotide polymorphism-based quantitative trait loci mapping revealed a genetic deletion that resulted in expression of a hypomorphic desmoglein 3 protein with a truncation of an extracellular cadherin domain. Because hypomorphic expression of a truncated desmoglein 3 protein led to a spectrum of severe pathology not observed in mice deficient in desmoglein 3, similar human genetic alterations may also disrupt desmosome function and induce a disease course distinct from pathogenesis of pemphigus vulgaris.

Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100.

Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor κB pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency.

Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice.

Aiming to decipher immunological mechanisms of the autoimmune disorder alopecia areata (AA), we hypothesized that interleukin-6 (IL-6) might be associated with juvenile-onset AA, for which there is currently no experimental model. Upon intramuscular transgenesis to overexpress IL-6 in pregnant female C57BL/6 (B6) mice, we found that the offspring displayed an initial normal and complete juvenile hair growth cycle, but developed alopecia around postnatal day 18. This alopecia was patchy and reversible (non-scarring) and was associated with upregulation of Ulbp1 expression, the only mouse homolog of the human AA-associated ULBP3 gene. Alopecia was also associated with inflammatory infiltration of hair follicles by lymphocytes, including alpha-beta T cells, which contributed to surface hair loss. Despite these apparently shared traits with AA, lesions were dominated by follicular dystrophy that was atypical of human AA disease, sharing some traits consistent with B6 alopecia and dermatitis. Additionally, juvenile-onset alopecia was followed by complete, spontaneous recovery of surface hair, without recurrence of hair loss. Prolonging exposure to IL-6 prolonged the time to recovery, but once recovered, repeating high-dose IL-6 exposure de novo did not re-induce alopecia. These data suggest that although substantial molecular and cellular pathways may be shared, functionally similar alopecia disorders can occur via distinct pathological mechanisms.

Gender differences in disease activity and clinical features in newly diagnosed systemic lupus erythematosus patients.

OBJECTIVE: The objective of this paper is to compare disease activity and clinical features at diagnosis in male and female patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional study in which every male patient (n = 40) was matched with three female patients of the same age (±5 years) and racial/ethnic group; disease activity as per the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and disease manifestations at the time of diagnosis were compared. RESULTS: Alopecia and anti-Ro antibodies were more frequent in female patients. No statistically significant difference in any other disease characteristics was found. However, male gender was associated with a risk of severe disease activity at the time of diagnosis (as determined by SLEDAI ≥12 score) independent of age, racial/ethnic group, anti-Ro positivity or time to criteria accrual (OR: 3.11 95% CI, 1.09-8.92; p = 0.035). CONCLUSION: In newly diagnosed SLE patients, male gender is associated with higher disease activity despite the fact that male and female patients seem to experience similar overall disease manifestations.