Naoka Umemoto

Paraneoplastic pemphigus mimicking erosive mucosal lichen planus associated with primary hepatocellular carcinoma

A 58‐year‐old Japanese male visited us with painful lesions on the lower lip, oral mucosa and genital region of an 8‐month duration. Histological features of the genital lesion were almost consistent with lichenoid tissue reaction. A few intraepidermal acantholytic keratinocytes were also seen in the suprabasal clefts. Direct immunofluorescence exhibited cell surface immunoglobulin (Ig)G deposition and linear deposition of fibrinogen at the dermoepidermal junction. IgG anti‐desmoglein (Dsg)3 antibody, but not anti‐Dsg1 antibody, was detected in the patients serum by enzyme‐linked immunosorbent assay. Immunoblotting using normal human epidermal extract detected the 210‐kD envoplakin, 190‐kD periplakin and 130‐kD Dsg3. The diagnosis of paraneoplastic pemphigus (PNP) was made. Subsequent investigation revealed a large space‐occupying lesion in the liver. Histological findings from liver biopsy specimen were consistent with hepatocellular carcinoma. The patient has been alive 38 months after the diagnosis of PNP was made, although the liver mass has slowly enlarged. Our case is clinically and histologically similar to erosive mucosal lichen planus. Immunological studies confirmed the diagnosis of PNP. The results of negative Dsg1 and positive Dsg3 were consistent with clinical features showing severe mucosal involvement without cutaneous erosion. In PNP, the association with non‐hematological solid tumor is extremely rare.

Serum levels of vasoactive intestinal peptide are elevated in patients with atopic dermatitis

Vasoactive intestinal peptide (VIP) has been suggested to play some roles in atopic dermatitis. Tissue of VIP levels has been reported to increase in chronic lichenified lesions of atopic dermatitis (AD). To analyze whether serum levels of VIP in AD patients are elevated compared with normal controls and correlated with the disease severity, we measured serum levels of VIP using enzyme-linked immunosorbent assay in 53 patients with AD and 21 healthy individuals. The results showed that serum levels of VIP in AD patients (345.8+/-71.5 microg/ml) were significantly higher than those in healthy individuals (307.1+/-42.6 microg/ml). However, a correlation was not found between serum VIP levels and disease severity, other markers including serum LDH levels, total serum IgE levels, and peripheral blood eosinophil counts in patients with AD. This indicates that VIP levels in AD patients were elevated not only in the skin but also in the serum, suggesting that increased serum VIP levels in the patients with AD might be involved in its pathogenesis.

Urticarial vasculitis presenting as erythema gyratum repens‐like eruption

© 2008 The Authors JEADV 2009, 23, 169–243 Journal compilation

A Case of Nonscarring Subepidermal Blistering Disease Associated with Autoantibodies Reactive with Both Type VII Collagen and Laminin 5

A 35-year-old Japanese woman had recurrent, pruritic, vesicular lesions on the face, neck and upper back as well as erosive lesions of the oral cavity and genitalia. The skin and mucosal lesions healed without scarring upon the systemic administration of corticosteroid and azathioprine. Direct immunofluorescence revealed linear deposits of IgG, IgA and C3 at the cutaneous basement membrane zone. Indirect immunofluorescence on 1 M NaCl-split human skin sections demonstrated that the patient’s IgG antibodies reacted with the dermal side of the split, while IgA antibodies weakly reacted with the epidermal side. By immunoblot analyses, the patient’s serum reacted with the NC1 domain of type VII collagen as well as both the α3- and β3-subunits of laminin 5. We regarded our case as a nonscarring subepidermal blistering disease with autoantibodies to both type VII collagen and two different subunits of laminin 5. Such a case has not been previously reported.

A case of mixed bullous disease of epidermolysis bullosa acquisita and linear IgA bullous dermatosis.

A 75-year-old Japanese male visited us with bullous eruptions on the extremities. Physical examination revealed large bullae on the hands, lower legs and feet. The oral mucosa was also involved. Histology disclosed subepidermal blister with inflammatory cell infiltrates in the dermis. Direct immunofluorescence showed deposits of IgG and IgA at the cutaneous basement membrane zone. Indirect immunofluorescence on 1 M NaCl-split human skin sections demonstrated that the patient’s IgG antibodies reacted with the dermal side of the split, while IgA antibodies reacted with the epidermal side. Immunoblotting showed that the patient’s serum reacted with the NC1 domain of type VII collagen (290-kDa epidermolysis bullosa acquisita antigen) as well as the 120-kDa linear IgA bullous dermatosis antigen, LAD-1. Systemic prednisolone resulted in a favorable response. From the clinicopathological findings, the present case is not consistent with either epidermolysis bullosa acquisita or IgA bullous dermatosis. Therefore, we regarded the case as mixed bullous disease of epidermolysis bullosa acquisita and linear IgA bullous dermatosis. Such a case has not been previously reported.

Possible paraneoplastic syndrome case of bullous pemphigoid with immunoglobulin G anti-BP180 C-terminal domain antibodies associated with psoriasis and primary macroglobulinemia.

A 61‐year‐old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl‐split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme‐linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M‐proteinemia of IgM‐κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C‐terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti‐BP180 C‐terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris.

A case of mucous membrane pemphigoid with IgG antibodies against all the α3, β3 and γ2 subunits of laminin-332 and BP180 C-terminal domain, associated with pancreatic cancer

A 66-year-old Japanese man presented with a 2-monthhistory of recalcitrant erosive rhinitis and stomatitis. On physical examination, he was found to have multiple irregularly shaped ulcers on the oral mucosae (Fig. 1a). Several tense bullae overlying erythema and skin ulcers were seen on the forearms and the left great toe (Fig. 1b). On histological examination of a biopsy taken from a lesion, a subepidermal blister was found, with numerous apoptotic keratinocytes on the roof (Fig. 2). ELISA using the recombinant protein of the bullous pemphigoid (BP)180 NC16a domain and desmoglein-3 gave negative results. Direct immunofluorescence revealed linear deposits of IgG, IgA, C1q, C3 and fibrinogen at the basement membrane zone (BMZ). Indirect immunofluorescence (IIF) detected IgG anti-BMZ antibodies, which reacted with both the epidermal and dermal sides of skin split with 1 mol ⁄ L NaCl. IIF using rat bladder section was positive. Using immunoblotting analysis, IgG antibodies to the 190-kDa periplakin were detected and IgA antibodies to BP230 and the 190-kDa periplakin using human epidermal extract (Fig. 3a) and IgG antibodies to all the a3, b3 and c2 subunits using purified laminin-332 (Fig. 3b). In addition, recombinant proteins of the BP180 NC16a domain and BP180 C-terminal domain gave positive IgG reactions to the BP180 C-terminal domain (Fig. 3c) and negative IgG and IgA reactions to the BP180 NC16a domain (data not shown). The patient was diagnosed with mucous membrane pemphigoid (MMP). Other investigations including computed tomography revealed a mass in the pancreas, which was histologically diagnosed as pancreatic carcinoma by biopsy. Betamethasone 4 mg daily and plasma exchanges slightly improved the mucosal and skin lesions, but the patient died of intrahepatic cholangitis followed by sepsis 4 months after his first visit to us. Anti-laminin-332 MMP is an autoimmune subepidermal blistering disorder that primarily involves the mucosal surfaces and has an increased relative risk for cancer. Our case was characterized by the presence of IgG antibodies against all the a3, b3 and c2 subunits of laminin-332 and (a)

Two cases of cutaneous phaeohyphomycosis due to Exophiala jeanselmei: diagnostic significance of direct microscopical examination of the purulent discharge.

Phaeohyphomycosis (PHM) is a fungal skin infection, usually caused by Exophiala jeanselmei. The disease is characterized by a cutaneous or subcutaneous nodule, which predominantly occurs on the exposed areas of the skin surface, particularly the limbs. PHM is known to arise at the site of trauma and often occurs in immunocompromised hosts such as those under treatment with systemic corticosteroid, recipients of organ transplantation or people with haematological malignancies. Generally, the diagnosis of PHM is confirmed by histological examination, which reveals the morphology of fungal elements in the tissue, and by mycological findings. There have been few reports about direct microscopical examination of the purulent discharge for the early diagnosis of PHM, although the usefulness of the direct potassium hydroxide (KOH) test for detecting sclerotic cells in chromomycosis is well known. We report two cases of PHM due to E. jeanselmei in immunocompromised patients and emphasize the usefulness for the diagnosis of PHM of direct microscopical examination of discharge from skin lesions. Patient 1 was a 75-year-old Japanese man, who was referred to our department with a subcutaneous abscess on the left lower leg. He had first noticed the lesion 1 week previously, but was uncertain about the precise onset of the skin lesion because it was asymptomatic. The patient had

Coexistence of paraneoplastic pemphigus and bullous pemphigoid

© 2009 The Authors JEADV 2009, 23, 954–982 Journal compilation

Urticarial vasculitis with haemorrhagic vesicles successfully treated with reserpine.

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