Toshifumi Yamaoka

Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort

Dermatomyositis (DM) is a heterogeneous disease with varying degrees and time courses of skin eruptions, myositis and internal organ involvement.1 Increasing evidence has demonstrated that myositis-specific autoantibodies (MSAs) are closely associated with distinct clinical subsets.2 Recently, Betteridge et al 3 ,4 reported a novel MSA against small ubiquitin-like modifier activating enzyme (SAE) in DM patients. In this study, we detected this autoantibody in a Japanese DM cohort and assessed its clinical correlations. We screened 456 consecutive Japanese patients with DM (11 children, 445 adults); 373 fulfilled the criteria of Bohan and Peter5 ,6 and the remaining 83 fulfilled Sontheimers criteria for clinically amyopathic DM (CADM).7 Controls included 62 patients with polymyositis, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with interstitial lung disease (ILD) alone. The institutional review board approved the study protocol. Immunoprecipitation assays were performed as described.8 Protein A-agarose beads preincubated with sera were incubated with 35S-methionine-labelled or unlabelled K562 cell extracts. Immunoprecipitants were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by autoradiography or …

Prevalence and Impact of Past History of Food Allergy in Atopic Dermatitis

BACKGROUND Increases in allergic diseases have been reported from various epidemiological surveys. However, a few reports demonstrate the comorbidity of food allergy (FA) and allergic march. The aim of this study was to assess the prevalence and comorbidity of allergic diseases in Japanese students. METHODS First-year students (n = 3,321; 2,209 male and 1,112 female) at Osaka University were asked about allergic diseases using postal interview sheets. Personal and family histories of doctor-diagnosed allergic diseases, clinical courses, and aggravating factors were included in the questionnaires. RESULTS The lifetime prevalence of allergic rhinitis (AR), atopic dermatitis (AD), bronchial asthma (BA), and FA was 35.7%, 16.5%, 9.9%, and 7.0%, respectively. Disease-specific family histories existed for AR, AD, and BA. There was a positive correlation between the number of family histories of allergic disease and comorbidity (R = 0.370, P <0.001). Comorbidity with AD significantly lowered the onset age of both BA (P = 0.010) and AR (P <0.001). In addition, the onset age of AD was remarkably lowered by comorbidity with FA (P <0.001). Comorbidity with FA was the highest risk factor for the progression of allergic march. Although most students showed improvement in AD, BA, and AR over time, the peak recurrence period was observed in adolescence. CONCLUSIONS These findings indicate that AD associated with FA accelerates the subsequent progression of allergic march. Early appropriate management for genetically high-risk groups is important for the prevention of allergic march.BACKGROUND Increases in allergic diseases have been reported from various epidemiological surveys. However, a few reports demonstrate the comorbidity of food allergy (FA) and allergic march. The aim of this study was to assess the prevalence and comorbidity of allergic diseases in Japanese students. METHODS First-year students (n = 3,321; 2,209 male and 1,112 female) at Osaka University were asked about allergic diseases using postal interview sheets. Personal and family histories of doctor-diagnosed allergic diseases, clinical courses, and aggravating factors were included in the questionnaires. RESULTS The lifetime prevalence of allergic rhinitis (AR), atopic dermatitis (AD), bronchial asthma (BA), and FA was 35.7%, 16.5%, 9.9%, and 7.0%, respectively. Disease-specific family histories existed for AR, AD, and BA. There was a positive correlation between the number of family histories of allergic disease and comorbidity (R = 0.370, P < 0.001). Comorbidity with AD significantly lowered the onset age of both BA (P = 0.010) and AR (P < 0.001). In addition, the onset age of AD was remarkably lowered by comorbidity with FA (P < 0.001). Comorbidity with FA was the highest risk factor for the progression of allergic march. Although most students showed improvement in AD, BA, and AR over time, the peak recurrence period was observed in adolescence. CONCLUSIONS These findings indicate that AD associated with FA accelerates the subsequent progression of allergic march. Early appropriate management for genetically high-risk groups is important for the prevention of allergic march.

Successful Treatment with Regimen of Intravenous Gammaglobulin and Cyclophosphamide for Dermatomyositis Accompanied by Interstitial Pneumonia, Opportunistic Infection and Steroid Psychosis

BACKGROUND A 47-year-old Japanese woman was suffering from dermatomyositis with progressive interstitial pneumonia, which was resistant to treatment with prednisolone (Pred) and cyclosporine A (CsA). Unfortunately, the opportunistic infection and steroid psychosis made therapeutic intervention using additional immunosuppressive drugs problematic. To overcome these difficulties, we created a regimen of intravenous gammaglobulin (IVIG) and cyclophosphamide (CPM) for the treatment of this patient. METHODS For the simultaneous treatment, IVIG-CPM was added to Pred/CsA by means of infusion of IVIG on five consecutive days per month, followed by CPM infusion on the ninth day after the last IVIG administration. The treatment was repeated for four months. RESULTS This regimen induced almost full remission without exacerbation of the opportunistic infection or mental disturbance. CONCLUSIONS The outcome reported here suggests that the combination therapy of Pred/CsA and IVIG-CPM appears to be useful for the treatment of dermatomyositis with pulmonary, infectious and mental complications.

Idiopathic pure sudomotor failure responding to oral antihistamine with sweating activities.

© 2014 The Authors. doi: 10.2340/00015555-1820 Journal Compilation

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO‐1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO‐1 stimulator and HO‐1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor‐α, interleukin‐6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO‐1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO‐1 inhibitor. These results suggest that the HO‐1/CO signalling pathway is a therapeutic target for human IC‐mediated disease.

Occult HIV infection in Japanese rupioid psoriasis

Dear Editor, Recently, the number of HIV-infected patients has been rising in Japan; however, HIV screening is not mandatory for biologic therapies of psoriasis. We herein report a patient with psoriasis who was found to have a HIV infection by a screening test before the initiation of biologic therapy. A 45-year-old Japanese man had sex with an unspecified large number of women while he worked overseas. He developed erythema on the forehead and the extremities 6 months prior to his initial visit that spread all over his body within the next 3 months. Due to the exacerbation of the skin lesions and a persistent fever above 38°C, he visited the Department of Dermatology at Osaka University Hospital in March 2015. At the first visit, he presented with erythroderma (Psoriasis Area and Severity Index [PASI] score, 58.6), and dark-purple rupioid scales and crusts were distributed over the trunk and extremities (Fig. 1a,b). A skin biopsy performed on the scaling erythema plaque on the forearm revealed hyperkeratosis, parakeratosis, moderate acanthosis and loss of the granular layer (Fig. 1c). The upper dermis also showed edema and lymphocyte infiltration. Although the pathological hallmarks of psoriasis are neutrophilic microabscesses, these were not observed in our patient. However, we considered that he had psoriasis based on the clinical observation, and histologically psoriasiform dermatitis. Therefore, we planned to start biologic therapy. The laboratory data revealed that CD4 T-lymphocyte cell count (4 cells/lL) was low. His HIV RNA viral load was 1 826 962 copies/mL, confirming a diagnosis of HIV infection.

Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.

Microbial proteases degrade a variety of host proteins1–3. However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.

Anti-MDA5 antibody-positive dermatomyositis with lethal progressive interstitial lung disease and advanced gastric cancer.

Dermatomyositis (DM) is an autoimmune inflammatory disease often associated with internal malignancy and interstitial lung disease. The latter is found in about 50% of patients with DM and is a life-threatening complication of the disease [1]. Rapidly progressive interstitial lung disease (RP-ILD) associated with clinically amyopathic dermatomyositis (CADM) is often lethal, despite treatment by corticosteroid therapy combined with immunosuppressive drugs [2].A number of autoantibodies can be detected [...]

The roles of P- and E-selectins and P-selectin glycoprotein ligand-1 in primary and metastatic mouse melanomas

BACKGROUND Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. OBJECTIVE To evaluate the role of adhesion molecules, including P-selectin glycoprotein ligand-1 (PSGL-1), P-selectin, and E-selectin. METHODS Subcutaneous primary growth and metastasis to the lung of B16 melanoma cells were examined in mice lacking PSGL-1, P-selectin, or E-selectin. RESULTS Primary subcutaneous growth of B16 melanoma was augmented by loss of PSGL-1, P-selectin, or E-selectin, while pulmonary metastasis was reduced by the loss of E-selectin. The enhancement of subcutaneous tumor growth was associated with a reduced accumulation of natural killer cells, CD4(+) T cells and CD8(+) T cells, while the attenuation of pulmonary metastasis was related to the numbers of CD8(+) T cells. The expressions of transforming growth factor (TGF)-β and interleukin (IL)-6 were correlated with primary subcutaneous growth; TGF-β, IL-6, and interferon-γ were related to number of metastatic lung nodules. Cytotoxicity against melanoma cells in splenocytes and in tumor-draining lymph node cells were not defective by the absence of adhesion molecules, suggesting that the enhancement of tumor growth and metastasis caused by the loss of selectins results from an impaired migration of effector cells into the tissue. CONCLUSIONS The results indicate the complexity of anti-tumor responses mediated by adhesion molecules in primary subcutaneous tumors and pulmonary metastasis of murine experimental melanoma.

Severe rosacea with prominent Demodex folliculorum in a patient with HIV

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