An epidemiological survey of anhidrotic/hypohidrotic ectodermal dysplasia in Japan: High prevalence of allergic diseases.

Anhidrotic/hypohidrotic ectodermal dysplasia (A/HED) is a congenital disorder characterized by anhidrosis/hypohidrosis and inadequate hair and dental dysplasia. Large-scale case studies of patients with A/HED have already been conducted overseas, while there has been no large-scale study, but only a few case reports in Japan. Furthermore, an epidemiological study of this disease has not been conducted in Japan to date. The purpose of this study was to investigate the clinical characteristics of A/HED patients, the status of genetic aberrations and complications of A/HED in Japan. Initially, we conducted a physician-initiated questionnaire survey of A/HED patients who visited medical institutions across Japan to investigate their backgrounds, clinical symptoms, genotypes, diagnostic methods and complications of A/HED. We also investigated the presence or absence of various allergic diseases (atopic dermatitis-like skin manifestations, bronchial asthma and food allergies). Questionnaires were also obtained from 26 patients with ectodermal dysplasia (ED) who visited four medical institutions. We compared the incidence of allergic diseases in healthy controls in a similar study to that of patients. Twenty-four of those patients were considered to have A/HED, of which 18 had a confirmed genetic diagnosis and were genotyped. All patients had anhidrosis or hypohidrosis, hair and dental dysplasia, and unique facial appearance; 23 patients had several cutaneous manifestations and seven patients had periorbital pigmentation. In addition, there was a significantly higher incidence of atopic dermatitis-like cutaneous manifestations, bronchial asthma and food allergies in the A/HED patients than in healthy controls. We report the results from a questionnaire survey of 24 patients with A/HED. This is the first report of a large number of A/HED patients in Japan. This study clarifies the status of clinical diagnosis and genetic testing of A/HED patients in Japan, as well as the characteristics of their skin symptoms and allergic complications.

Prognosis after steroid pulse therapy and seasonal effect in acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis is a rare disease with unknown etiology. Sudden loss of sweating function adversely affects young patients' quality of life. Although systemic corticosteroid therapy is the most frequently reported treatment for the disease, its effectiveness is controversial because of the risk of recurrence. To assist clinical decision-making regarding whether to use steroids, we investigated the treatment responsiveness and recurrence rates in patients undergoing steroid pulse therapy and explored factors affecting these rates. We retrospectively collected data of 124 patients who received steroid pulse therapy to calculate the rate of responsiveness to the therapy. We also conducted a time-to-event analysis in a cohort of 57 patients who responded to steroid pulse therapy to estimate the recurrence rate after the therapy. As a result, the response and recurrence rates were 73% and 48%, respectively. Recurrence occurred within 1 year in most patients. The overall effectiveness of steroid pulse therapy was estimated to be 57% considering the recurrence rate. A delay from onset to treatment and younger age appeared to be negative factors for effectiveness. Moreover, we found a significant seasonal effect on both treatment and recurrence: autumn was the worst season for acquired idiopathic generalized anhidrosis in Japan. Our study revealed that steroid pulse therapy can be expected to be effective in half of treated patients. We recommend starting the therapy promptly after the diagnosis; however, it is also worth considering the season for treatment planning.

Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment.

Sweat includes active components and metabolites, which are needed to maintain skin homeostasis. Component changes in sweat derived from atopic dermatitis (AD) have been reported. To investigate the influence of sweat components on the pathogenesis of AD, we performed a multifaceted assessment, including nuclear magnetic resonance spectroscopy-based metabolomic analysis, and linked these features to clinical features of AD. Distinctive properties of AD sweat are the quite-variation in protein, anti-microbial peptides and glucose concentrations. pH, sodium, and other salt levels in sweat of AD were comparable to that of healthy subjects. Sweat from AD patients with acute inflammation had a more prominent increase in glucose concentration than sweat from healthy individuals or those with AD with chronic inflammation. Topical glucose application delayed recovery of transepidermal water loss in barrier-disrupted mice. Furthermore, the glucose transporter GLUT2 was highly expressed in the lumen of sweat glands from AD patients. AD patients with chronic inflammation had significantly increased GLUT2 mRNA expression and near normal sweat glucose levels. Despite the small sample size in our study, we speculate that the increased glucose levels might be affected by AD severity and phenotype. We hope that this report will bring novel insight into the impact of sweat components on the clinical manifestation of AD.

Evaluation of the correlation between severity of acquired idiopathic generalized anhidrosis and quality of life scores.

Symptoms of acquired idiopathic generalized anhidrosis (AIGA) include heat retention and/or heat stroke due to the effects of the disorder on the perspiration ability of the whole body under thermal environmental changes or exercise. Additionally, cholinergic urticaria can also occur in these patients. AIGA has a major impact on everyday life. However, the effects of AIGA severity on the quality of life (QOL) of the patients have not been sufficiently defined. The objective of this study was to evaluate the correlation between AIGA severity and QOL. Study subjects comprised 44 patients diagnosed with AIGA at three registered institutions. AIGA severity assessment was conducted and the Dermatology Life Quality Index (DLQI) questionnaire was administered. Correlations between AIGA severity and DLQI, as well as severity by DLQI subscale, were assessed. We found a positive correlation between total score of AIGA severity criteria and DLQI total scores (R = 0.720, P = 0.001). The impairment increased with the increase in AIGA severity (P < 0.01). In relation to the DLQI subscales, leisure (social and sporting activities) impairment was significantly higher for patients with severe AIGA than those with mild AIGA (P < 0.01). Comparing QOL for AIGA patients with that of patients with other dermatological disorders, it is possible that QOL impairment for AIGA patients is as severe as that for patients with atopic dermatitis. AIGA severity and DLQI are correlated and AIGA patients experience disruption of everyday life more broadly than conventionally perceived.

Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by an acquired impairment in total body sweating despite exposure to heat or exercise. Severe cases may result in heatstroke. Most cases of AIGA have been reported in Asia, especially in Japan. However, there is limited information on the epidemiology of this condition, and no diagnostic criteria or appropriate treatment options have been established. This guideline was developed to fill this gap. It contains information on the etiology, diagnosis, evaluation of disease severity and evidence-based recommendations for the treatment of AIGA. Appropriate treatment according to disease severity may relieve the clinical manifestations and emotional distress experienced by patients with AIGA.

Basophils and mast cells are crucial for reactions due to epicutaneous sensitization to ovalbumin.

The prevalence of food allergies worldwide has increased recently. Epicutaneous sensitization to antigen could be a method to study food allergy. To clarify the mechanisms of food allergy, we established a mouse model of epicutaneous sensitization using ovalbumin (OVA). BALB/c mice were sensitized by three-time application of OVA to tape-stripped skin (1-week sensitization at 2-week intervals) and oral challenge of OVA undertaken. Rectal temperature was monitored. Blood and tissue (skin and jejunum) of challenged mice were taken. Numbers of mast cells (MCs) and basophils were counted. Serum and/or tissue levels of OVA -specific IgE and IgG antibodies and several cytokines were measured using enzyme-linked immunoassay kits. MC and basophil depletion experiments were undertaken. In OVA/epicutaneous-sensitized and orally challenged mice, systemic anaphylaxis (as evidenced by reduced rectal temperature) was observed. Levels of OVA-specific IgE and IgG antibodies were increased in these mice, as were increased number of MCs and basophils. Serum levels of MC protease 1 were increased significantly. Basophil and MC depletion experiments revealed that they both participate in reactions. Increased production of thymic stromal lymphopoietin (TSLP) at skin sites of OVA sensitization was noted. We speculate that TSLP produced from epidermal cells during antigen sensitization can enable basophils to promote a T helper (Th)2 immune reaction, leading to and systemic anaphylaxis by antigen-specific IgE-bearing MCs. This TSLP-basophils-MC axis could be a novel therapeutic target against food allergy.