Satomi Hosoda

A Case of IgG/IgA Pemphigus Presenting Malar Rash-like Erythema

Pemphigus is an autoimmune mucocutaneous bullous disease characterized by auto-antibodies against cell surface antigens of epidermal keratinocytes. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the major subtypes. Several other variants have been proposed, in-cluding pemphigus erythematosus, pemphigus vegetans, pemphigus herpetiformis (PH), and paraneoplastic pem-phigus. Deposition of IgG on epidermal keratinocyte cell surfaces and circulating anti-cell surface antibodies are characteristic in pemphigus. Cases involving IgA depo-sition on epidermal keratinocyte cell surfaces have been reported as IgA pemphigus. IgA pemphigus is divided into 4 subgroups based on clinical manifestation: subcorneal pustular dermatosis type, intraepidermal neutrophilic IgA dermatosis type, pemphigus foliaceus type, and pemphi-gus vulgaris type. Cases involving deposition of both IgG and IgA on keratinocyte cell surfaces have been reported (1–13). Some authors describe them as IgG/IgA pemphi-gus (1). Seventeen such cases have been reported so far, and heterogeneity of clinical features and target antigen has been detected in this group of pemphigus. CASe RePoRT

Possible involvement of SDF-1/CXCL12 in the pathogenesis of Degos disease.

BACKGROUND Degos disease or malignant atrophic papulosis is a rare occlusive vasculopathic disease characterized by pathognomonic cutaneous lesions and frequently fatal systemic involvement. The etiology of malignant atrophic papulosis remains unclear, and there is currently no effective treatment for malignant atrophic papulosis. Several chemokines can potentiate and expand the platelet response to increase thrombus formation. Among these chemokines, this study examined the expression of stromal cell-derived factor (SDF)-1/CXCL12, which is secreted by bone-marrow stromal and endothelial cells, activates megakaryocyte precursors, and costimulates platelet activation. OBJECTIVE We sought to investigate and compare the expression of SDF-1/CXCL12 in tissue sections taken from 2 patients with Degos disease, 2 patients with other vaso-occlusive diseases, and 2 healthy control subjects. METHODS Immunohistochemical staining involving antibodies to SDF-1/CXCL12 was performed on 3 skin biopsy specimens taken from 2 patients with Degos disease, 1 from a patient with antiphospholipid syndrome, 1 from a patient with cryoglobulinemia, and 2 from healthy control subjects. RESULTS Strong SDF-1/CXCL12 staining was observed in the infiltrating inflammatory cells in the perivascular, intravascular, and perineural areas in tissue samples from patients with Degos disease. No staining was observed in samples from patients with antiphospholipid syndrome or cryoglobulinemia or from healthy control subjects. LIMITATIONS The number of cases available for evaluation was small. The findings were based primarily on the immunohistochemical results and were not confirmed using other techniques. CONCLUSIONS The intense staining of SDF-1/CXCL12 in lesions attributed to Degos disease, demonstrated for the first time to our knowledge in this study, suggests SDF-1/CXCL12 involvement in the pathogenesis of the disease.

Case of pemphigus with immunoglobulin G and A antibodies, binding to both the intercellular spaces and basement membrane zone.

We report a case involving a 62‐year‐old woman with in vivo‐bound immunoglobulin (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and histopathological features were identical with those of pemphigus vulgaris, while the immunopathological findings suggested IgG/IgA pemphigus. Direct immunofluorescence (IF) showed in vivo‐bound IgG and IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the ICS and BMZ. The anti‐ICS IgG bound to desmoglein‐3, while the anti‐BMZ antibodies bound to the epidermal side of 1 mol/L NaCl‐split skin. To the best of our knowledge, only two similar cases have been reported so far. Furthermore, we also examined IgG subclass distribution of the in vivo‐bound and circulating anti‐ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti‐ICS antibodies belonged to IgG1 and IgG4, while the circulating anti‐BMZ antibodies to IgG1, IgG2 and IgG4.

Distribution of basement membrane zone components in bullous lesions of subepidermal blistering diseases

Dear Editor, The differential diagnosis of autoimmune subepidermal bullous disease (ASBD) is sometimes difficult in cases with low or no circulating autoantibody activity. The skin samples were obtained from the lesional skin of 11 patients with ASBD (58–95 years of age; four males, seven females), together with sera, after written consent. All the skin samples were embedded in an optimal cutting temperature compound and frozen. The institutional ethical committee of Jichi Medical University approved this project. The glutathione-s-transferase (GST) fusion proteins corresponding to the NC16A domain, C-terminal portion of BP180 and BP230, spanning amino acids 490–582, 1080–1107 and 1861–1920, respectively, were generated as previously described. Rabbit antibodies to these fusion proteins were generated by Takara Bio (Otsu, Japan). Immunoblotting with these antibodies (0.1 mg/mL) demonstrated relevant results. These fusion proteins were immobilized on a 96-well polystyrene plate (0.05 lg/mL) and incubated with serially diluted (1:10–1:10) rabbit antibodies to each fusion protein, resulting in a dose-dependent reaction. Immunofluorescent (IF) staining of the patients’ skin samples was performed and observed using a fluorescence microscope (BZ 8000; Keyence, Osaka, Japan). The antibodies used in this study are summarized in Table 1.

Case of drug-induced hypersensitivity syndrome with multiple skin ulcers caused by herpes simplex virus reactivation.

as serum complements were normal. A diagnosis of adrenergic urticaria was made. Propranolol dinitrate 20 mg three times daily successfully prevented the urticaria and dermographism, however, withdrawal of propranolol led to recurrence. Adrenergic urticaria was first proposed to be contrasted with cholinergic urticaria (CU) as a distinct form of urticaria with a neural basis. CU can be triggered by stress or heat, with the characteristic appearance of a small papule in the center of a large bright-red flare of vasodilation. It represents a response to acetylcholine and can be replicated by an i.d. injection of acetylcholine. Our case of AU can be distinguished from CU by its distinctive clinical appearance and the halo on vasoconstricted skin induced by noradrenaline skin test. Dermographism has not been described in AU, except for a case showing negative dermographism. Our patient demonstrated scratching induced wheals, however, surrounded by blanched halos, instead of erythema in typical dermographism. More interestingly, i.d. saline induced blanched skin, which was consistent with white dermographism seen in atopic dermatitis. Thus, the scratching reaction of our patient could be interpreted as combined reaction of adrenergic urticaria and white dermographism. It has been shown that the acute psychosocial stress test does not alter the magnitude of the dermographic reactions. Thus, molecular interactions between adrenergic synapses and dermographic reaction are worth further investigation. Other atopic manifestations including multiple food and drug allergies were also presented by this patient. The pathogenesis of AU is largely unknown. Autonomic dysfunction and allergic theory have been proposed. More recently, autoimmune disorders have been noticed in AU. Chedraoui et al. reported an AU patient with positive double strand antinuclear antibody. Capella et al. reported a rheumatoid arthritis patient with AU. Thyroid autoimmunity has been associated with chronic idiopathic urticaria (CIU), with approximately one-quarter of the CIU patients having at least one thyroid autoantibody, although the mechanisms for this association are not clear. Our patient is the first report associating AU with positive thyroid autoantibody. Elevated serum TPOAb and decreased thyroxine level indicated subclinical autoimmune thyroid disease. Although the significance of this antibody warrants further investigation, it provides new evidence for the autoimmune basis in the pathogenesis of AU.

A case of dermatitis herpetiformis with blister formation between laminin‐332 and type 7 collagen

Dear Editor, We report on a 40-year-old Japanese man who visited a local hospital in January 2011, complaining of pruritic eruption on his trunk and his neck. He was diagnosed with dermatitis herpetiformis (DH) based on clinical and immunofluorescence findings and treated with diamino-diphenyl sulfone (DDS) (50 mg/day). His skin lesions disappeared, and the DDS was tapered down. In January 2013, he visited our department. His general condition was good without gastrointestinal symptoms, and his family history was unremarkable. Clinical examination revealed numerous annular erythemas with vesicles on his trunk (Fig. 1a, b). Skin biopsy from the trunk revealed subepidermal bullae and neutrophils at the tips of the papillary dermis (Fig. 1c). Direct immunofluorescence showed granular and fibrillar deposits of immunoglobulin A (IgA) at the papillary dermis. Indirect immunofluorescence, using normal skin sections as substrate, showed no circulating IgA antibodies at the intercellular space or basement membrane zone (BMZ). We performed immunomapping

Case of pemphigoid involving skin and mucous membrane with immunoglobulin G autoantibodies targeted to BP180 and laminin-332.

1 Sampogna F, Raskovic D, Guerra L et al. Identification of categories at risk for high quality of life impairment in patients with vitiligo. Br J Dermatol 2008; 159: 351–359. 2 Sukan M, Maner F. The problems in sexual functions of vitiligo and chronic urticaria patients. J Sex Marital Ther 2007; 33: 55–64. 3 Ongenae K, Dierckxsens L, Brochez L et al. Quality of life and stigmatization profile in a cohort of vitiligo patients and effect of the use of camouflage. Dermatology 2005; 210: 279–285. 4 Porter JR, Beuf AH, Lerner AB et al. The effect of vitiligo on sexual relationships. J Am Acad Dermatol 1990; 22: 221–222. 5 Holme SA, Beattie PE, Fleming CJ. Cosmetic camouflage advice improves quality of life. Br J Dermatol 2002; 147: 946–949.

Nadifloxacin downregulates the production of matrix metalloproteinases in the human epidermal keratinocyte cell line HaCaT.

Dear Editor, Nadifloxacin is a potent new quinolone antibiotic, approved for topical use in acne vulgaris patients in Japan. Matrix metalloproteinases (MMP) are enzymes effective in degrading the extracellular matrix (ECM), such as interstitial collagens and basement membranes and are abundantly found in acne lesions. These enzymes are thought to work in promoting inflammation and tissue remodeling, the exacerbating factors in scar formation. We investigated the effect of nadifloxacin on the production of MMP produced in HaCaT keratinocytes. HaCaT keratinocytes were a generous gift from Dr Kuroki (Showa University) with the permission of Dr Fusenig (Institute Fur Zellund Tumourbiologie, Deutsches Kresforschungszentrum, Heidelberg, Germany). The cells were seeded into 6-well plates and cultured with or without nadifloxacin, incubated overnight, and then stimulated with tumor necrosis factor (TNF)-a (10 ng ⁄ mL). The supernatants were collected after 48 h and subjected to enzyme-linked immunosorbent assay (ELISA). MMP-1, -9 and -13 ELISA Kits were from GE Healthcare Japan (Tokyo, Japan). The optical density of each well was determined using a microplate reader (Model 550; Bio-Rad, Richmond, CA, USA) set to 450 nm. Total RNA samples were isolated using ISOGEN (Nippon Gene, Tokyo, Japan). Reverse transcription was performed using the Superscript III RT Kit (Invitrogen Japan, Tokyo, Japan). The primers and probes for the MMP (TaqMan gene expression assays; MMP-9, Hs00957562 m1; MMP13, Hs00233992 m1; MMP-1, Hs00233958 m1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were obtained from Applied Biosystems (Norwalk, CT, USA). Real-time polymerase chain reaction (RT–PCR) and the analysis were carried out with an ABI PRISM 7000 sequence detector (Applied Biosystems) using the TaqMan RT–PCR Master Mix Reagents Kit (Applied Biosystems). All results are expressed as the mean ± standard deviation. Statistical comparisons were made by Mann–Whitney’s U-test. The results were considered significantly different at P < 0.05. HaCaT keratinocytes produced MMP-1, -9 and -13, which were induced by the addition of TNF-a. The level of MMP-13 was the highest among those of the MMP (Fig. 1a). The induction of MMP-9 by TNF-a was less when the cells were 100% confluent compared