Takichi Munetsugu

Three Cases of Linear IgA/IgG Bullous Dermatosis Showing IgA and IgG Reactivity With Multiple Antigens, Particularly Laminin-332

IMPORTANCE Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to epidermal basement membrane zone. The heterogeneity and pathogenesis of the LAGBD autoantigens have not been fully elucidated. OBSERVATIONS We report 3 Japanese cases of LAGBD (ages 81, 88, and 64 years; 1 woman and 2 men). The patients showed bullous and erosive lesions on the trunk and extremities with minimal mucosal lesions. Histopathological analysis revealed a subepidermal blister with neutrophilic infiltration with eosinophils in 2 cases. Direct and indirect immunofluorescence studies disclosed IgG and IgA antibasement membrane zone antibodies. In immunoblot analyses of various antigen sources, all cases showed IgG and IgA antibodies to various subunits of laminin-332, in addition to IgG and IgA reactivity with type VII collagen, laminin-γ1, and BP230 and BP180 recombinant proteins. CONCLUSIONS AND RELEVANCE Our studies revealed that the 3 LAGBD cases showed prominent IgG and IgA reactivity with laminin-332, which was only rarely reported. In addition, all cases showed IgG and IgA reactivity with other multiple antigens, indicating the role of epitope-spreading mechanisms initiated from laminin-332. The significance of IgA antibodies to laminin-332 should be studied in larger cohorts of both LAGBD and linear IgA bullous dermatosis.

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.

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.

A case of subungual melanoma with bone invasion: destructive local invasion and multiple skin metastases

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Acute infectious urticaria associated with human parvovirus B19 infection

Dear Editor, A 24‐year‐old woman presented with a two‐day history of fever and wheals. Physical examination demonstrated multiple wheals on her face, trunk, and extremities with severe itching (Figure 1A). Her body temperature was 38°C; however, she did not have any symptoms of upper respiratory tract infection. Two days after admission, she showed angioedema on her eyelid and lower lip (Figure 1B) and swelling of bilateral dorsal hands and feet (Figure 1C and D). The patient also had arthralgia on her wrists, ankles, and fingers. Laboratory data showed increased white blood cell count (15.1 × 10/μL; neutrophils 87%, eosinophils 0.2%) and C‐reactive protein (16.3 mg/dL). Investigations for viral titers demonstrated increased IgM antibody against human parvovirus B19 (HPVB19) (7.01; normal: <0.80). There were no significant changes in titers suggestive of other infectious agents, such as cytomegalovirus (CMV), EB virus (EBV), herpes simplex virus (HSV), or Mycoplasma pneumoniae. Notably, the patient showed increased coagulation/fibrinolysis markers: FDP, 83 μg/mL (normal: <5 μg/mL); D‐dimer, 46.8 μg/mL (normal: <0.1 μg/mL); and prothrombin fragment 1 + 2, 1,160 pmol/L (normal: 69–229 pmol/L). The patient was diagnosed with acute urticaria

Cold‐induced hyperhidrosis: possible association with hyper‐IgE syndrome

lesion, but it is highly probable. The suggested mechanism is that PDT may have triggered non-specifically BP in a predisposed patient. Another possibility is that it may have caused a direct injury to the basement membrane and subsequent antibody formation. The role of the curettage before the application of Metvix is open to discussion, but we did not find in the literature cases of BP associated with curettage or electrodessication. Overall, PDT should be added to the list of possible external triggers of BP.

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.