Hajime Shindo

Fur mites induce dermatitis associated with IgE hyperproduction in an inbred strain of mice, NC/Kuj

An inbred strain of mice, NC, has been introduced as an animal model for atopic dermatitis because the mice develop dermatitis associated with severe scratch preceded by elevated serum IgE level when kept in conventional conditions. Although hypersensitivity to some environmental factors is suggested to cause dermatitis, the precise factor remains unclear. As the mice maintained under conventional conditions were often infected with fur mites, we investigated whether an infection of fur mites induces skin lesions in NC. Infection with the fur mites induced NC to develop skin lesions associated with highly elevated serum IgE, whereas no obvious skin lesions were observed in BALB/c and C57BL/6, and the elevation of serum IgE level was minimal in these two strains of mice. The role of the fur mites in the manifestation of skin lesions and IgE hyperproduction was confirmed by eliminating the fur mites by treatment with ivermectin. In addition, the existence of specific IgE antibody to Myocoptes musculinus antigen in the sera of mite-infested NC was detected by the antigen-induced histamine release from bone marrow-derived cultured mast cells after sensitization with the serum. These results suggest that continuous exposure to fur mite antigen is a potential factor in the development of dermatitis in NC. We provide a new model system of antigen-induced dermatitis for investigating the role of IgE in eliciting dermatitis.

Metastatic extramammary Paget's disease treated with paclitaxel and trastuzumab combination chemotherapy.

In the treatment of metastatic breast cancer, trastuzumab, a recombinant monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is effective when tumor cells overexpress HER2 protein. Although some cases of extramammary Paget’s disease (EMPD) also express HER2 protein, no case of EMPD has been reported to be treated with trastuzumab. A 75‐year‐old man who suffered from EMPD of the scrotum and inguinal region underwent a local excision and lymph node dissection. Tumor cells invaded the dermis and lymph nodes. Although he was postoperatively treated with adjuvant chemotherapies, metastatic skin lesions appeared and spread over his left thigh, rapidly and widely. Tumor cells disseminated along lymph vessels in the dermis and overexpressed HER2 protein. We administered paclitaxel and trastuzumab according to a protocol for HER2‐positive metastatic breast cancers. The skin metastasis dramatically decreased during the regimen and a histopathological examination showed that most of HER2‐positive tumor cells diminished. Six months later, metastases were found in the central nervous system (CNS), but no other metastases were found in the skin, visceral organs or lymph nodes. Trastuzumab and paclitaxel‐combination with the assessment of central nervous system lesions should be considered as an option for the treatment of HER2‐positive EMPD.

Sweat antigen induces histamine release from basophils of patients with cholinergic urticaria associated with atopic diathesis

Background  We previously demonstrated that the semipurified human sweat antigen causes skin reactions and histamine release from basophils via specific IgE in patients with atopic dermatitis (AD). Patients with cholinergic urticaria (ChU) also develop skin reactions and histamine release of basophils in response to autologous sweat.

A randomized double-blind trial of intravenous immunoglobulin for bullous pemphigoid.

BACKGROUND Patients with steroid-resistant bullous pemphigoid (BP) require an appropriate treatment option. OBJECTIVE A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in BP patients who showed no symptomatic improvement with prednisolone (≥0.4mg/kg/day) administered. METHODS We evaluated the efficacy using the disease activity score on day15 (DAS15) as a primary endpoint, and changes in the DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days as secondary endpoints. RESULTS We enrolled 56 patients in this study. The DAS15 was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The mean DAS of the IVIG group was constantly lower than that of the placebo group throughout the course of observation, and a post hoc analysis of covariance revealed a significant difference (p=0.041). Furthermore, when analyzed only in severe cases (DAS≥40), the DAS15 differed significantly (p=0.046). The anti-BP180 antibody titers showed no difference between the two groups. CONCLUSION IVIG provides a beneficial therapeutic outcome for patients with BP who are resistant to steroid therapy.

A Case of SAPHO Syndrome With Diffuse Sclerosing Osteomyelitis of the Mandible Treated Successfully With Prednisolone and Bisphosphonate

*Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. †Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ‡Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. §Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ¶Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan. #Department of Dermatology, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. **Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ††Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ‡‡Department of Oral and Maxillofacial Surgery, Division of Cervico Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. Address correspondence and reprint requests to Dr Shigeishi: Department of Oral and Maxillofacial Surgery, Division of CervicoGnathostomatology, Graduate School of Biomedical Sciences, Hirod

The Sensitivity and Clinical Course of Patients with Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized to Hydrolyzed Wheat Protein in Facial Soap - Secondary Publication

BACKGROUND Recently, an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them had developed this condition during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA). METHODS To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we retrospectively studied the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. RESULTS Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of gluten-specific IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P < 0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced the highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap. CONCLUSIONS The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

Refractory Chronic Urticaria Treated Effectively with the Protease Inhibitors Nafamostat Mesilate and Camostat Mesilate

Chronic urticaria (CU) is characterized by the sponta-neous recurrent appearance of wheals and pruritus, which seriously impairs patients’ quality of life (QoL) (1, 2). Patients with refractory CU are treated with leukotriene receptor antagonists, glucocorticoids and/or other im-munomodulatory agents in addition to antihistamines (3, 4). Nevertheless, there remain a number of patients who are unsatisfactorily treated even with these medications, either due to insufficient efficacy or to the occurrence of side-effects. Nafamostat mesilate (NM) and camostat mesilate (CM) are newly synthesized protease inhibitors. They inhibit broad serine proteases, including trypsin, kallikrein, complements (C1r

Neutrophilic lobular panniculitis with non-rheumatoid arthritis.

A 55-year-old woman presented with multiple lesions of desquamous or non-desquamous erythema (0.5–1 cm in diameter) with slightly subcutaneous indurations on upper and lower extremities (Fig. 1). The patient felt mild heat and pain around the lesions. Neither petechiae nor signs of trauma were observed. She had suffered from these lesions for 5 months. Some of them had spontaneously regressed, while others appeared elsewhere. She had been suffering from sharp pain in her right knee joint for more than 10 years. However, clinical examination and knee joint X-ray, complete blood cell count, C-reactive protein, rheumatoid factor, anti-nuclear antibody and other serum biochemistry analyses showed no abnormality that suggested rheumatoid arthritis or collagen diseases. Histological examination of a lesion on the right leg revealed distinctive lobular panniculitis (Fig. 2). A small but extensive infiltration of neutrophils with nucleus

A unique clinical phenotype of a patient bearing a newly identified deletion mutation in the PSENEN gene along with the pathogenic serum desmoglein-1 antibody

these cells were strongly positive for CD123, CD138, CD33 and myeloperoxidase, which are markers that are frequently expressed on leukaemia blast cells (Fig. 2b–d). A bone marrow biopsy confirmed the suspected diagnosis of AML (subtype M2 of the French–American–British classification). A diagnosis of unusual LC in AML was made, and chemotherapy with 5-azacytidin was initiated, resulting in a rapid reduction of peripheral blood blast cells as well as clinical improvement of the leg ulcer. However, the patient died 2 months later because of progression of his AML. LC most frequently occurs in chronic lymphocytic leukaemia and AML. In a large study of 381 patients with AML, LC was found in 14 (3.7%), but only 1 had AML subtype M2. In the majority of cases, LC is observed in patients who already have a diagnosis of leukaemia, whereas simultaneous manifestation of cutaneous and systemic involvement is less frequent (approximately 25%). LC preceding haematological detection of leukaemia in the peripheral blood or bone marrow, as seen in our patient, is very rare. LC may present as localized or generalized lesions, with the latter occurring predominantly in acute types of leukaemia. Clinically, LC most frequently manifests as papules, nodules or plaques with a characteristic reddish or violaceous colour. Interestingly, specific leukaemic infiltrates also manifest at sites of previous trauma, within lesions of inflammatory skin diseases and in skin tumours. It has been reported that complex chemokine/chemokine-receptor interactions (e.g. CCR5, CXCR4, CXCR7, and CX3CR1) orchestrate the migration of leukaemic cells to the skin, a phenomenon called ‘skin selective homing’. Accordingly, local trauma and venous insufficiency might have been predisposing factors for homing and retention of AML blast cells in our patient’s leg ulcer. Prognosis of LC is usually poor, and it has been reported that up to 90% of patients will die within the first year after their diagnosis of LC, especially patients with AML.

Balloon Cell Malignant Melanoma in a Young Female: A Case Report and Review of the Literature

Balloon cell malignant melanoma (BCMM) is a very rare malignant melanoma subtype. The clinical appearance of BCMM varies; it may be nodular, ulcerated, polypoid, papillomatous and often non-pigmented. The tumor cells histologically appear large, polygonal or round and contain abundant granular or vacuolated cytoplasm. We herein report the case of a 32-year-old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years. She underwent tumor excision. The histopathological analysis showed epithelioid melanocytes with clear cytoplasm. An immunohistochemical analysis revealed that the cells were positive for HMB-45 and S-100 protein and negative for cytokeratin. The balloon cell component stained negative for Fontana-Masson. A month later, the patient underwent excision of the bilateral inguinal lymph nodes and metastatic BCMM was revealed. The lymph node metastases showed the complete replacement of lymph nodes by balloon cells. A diagnosis of BCMM (Breslow depth 10 mm, Clark level V) without ulcer was rendered. Staining with Ki-67 was positive in almost 44% of the balloon cells.