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Fabry disease (FD), which is a lysosomal storage disease resulting from a deficiency of α-galactosidase A, leads to the accumulation of globotriaosylceramide in various tissues and multiorgan impairment. Early diagnosis is important to improve long-term prognosis. Early clinical manifestations of FD include neuropathic pain, vascular skin lesions, and sweating abnormalities. Hypohidorosis is one of the clinical findings in the early stage of FD. However, there have been no studies on prospective screening of FD in patients with definitive diagnosis of hypohidrosis. We examined α-galactosidase A activity in white blood cells in 17 (one female and 16 male) patients with generalized hypohidorosis. Among 17 patients, one male patient (approximately 5.8%) had significantly reduced α-galactosidase A activity. He presented with a history of hypohidrosis with heat intolerance and neuropathic tingling pain in a warm environment from 6 years ago. He had a few angiokeratoma on the trunk and extremities. Ultrastructural examination of skin biopsy from the angiokeratoma revealed lamellar inclusions in endothelial cells. Kidney biopsy revealed swollen podocytes and Gb3 deposition in the glomerulus, and urinalysis revealed mulberry bodies. He was finally diagnosed with FD and started on enzyme replacement therapy with agalsidase alpha in the early stage. In addition, his family screening led to find the patients of four additional FD. Screening for FD in patients with hypohidrosis may lead to efficient early detection of FD.

Purpose: The aim of this study was to review the evidenceon the epidemiology, physiopathology, categorization, andmanagement of cholinergic urticaria. We specificallyfocused on several subtypes of cholinergic urticaria andinvestigated the relationship between cholinergic urticariaand idiopathic anhidrosis.Methods: Using an integrative approach, we reviewedpublications addressing the epidemiology, clinical features,diagnostic approach, physiopathology, subtype classifica-tion, and therapeutic approach to cholinergic urticaria.Results: Multiple mechanisms were found to contribute tothe development of cholinergic urticaria. This disordershould be classified based on the pathogenesis and clinicalcharacteristics of each subtype. Such a classification sys-tem would lead to better management of this resistantcondition. In particular, sweating function should be givenmore attention when examining patients with cholinergicurticaria.Conclusions: Because cholinergic urticaria is not a homo-geneous disease, its subtype classification is essential forselection of the most suitable therapeutic method

Purpose of review This review aims to update the information and latest advances in chronic inducible urticarias. Recent findings In contrast to chronic spontaneous/idiopathic uriticarias, chronic inducible urticarias are associated with a specific trigger and factor. One must accurately identify and characterize the specific trigger for distinguishing chronic spontaneous/idiopathic uriticaria and chronic inducible urticarias. The latter are diagnosed based on patient history and results of provocation testing which contribute to confirm the exact diagnosis, assess the threshold, and determine the severity of the disease. The general management of chronic inducible urticarias includes the identification and avoidance of the specific trigger, and symptomatic treatment with the goal of reaching complete symptom control. Symptomatic treatment for chronic inducible urticarias targets the blocking of mast-cell mediators (H1-antihistamines, H2-antihistamies, leukotriene antagonists) and inhibition of mast-cell activation (omalizumab, cyclosporine, phototherapy). H1-antihistamines are fundamental treatments for chronic inducible urticarias, but H1-antihistamine-resistant cases are not rare and additional treatment is often necessary. Also, therapeutic reactivity varies according to each subtype and patient. Summary Notably, some subtypes of chronic inducible urticaria can be treated by desensitization and/or tolerance induction to triggers. In contrast, the underlying pathogenesis of chronic inducible urticaria is not known and further studies are needed to better clarify its etiology.

Anti-tumor necrosis factor (TNF)-α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome-wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti-TNF-α therapy using Human Omni Express-8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti-TNF-α agents (strongest effect, P < 7.11E-06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti-TNF-α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF-α production, was previously reported to be associated with treatment responses to TNF-α inhibitors.

Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis.