Maki Kakurai

Activation of mast cells by silver particles in a patient with localized argyria due to implantation of acupuncture needles

An 83-year-old Japanese woman presented with multiple bluish-black macules and nodules with intense pruritus on the lower back (Fig. 1). She had received acupuncture therapy 20 years previously because of lower back pain. Histology showed a foreign body reaction and brownish pigmented particles in the dermis. Numerous mast cells were found around the pigmented particles. In electron microscopy, mast cells containing electron-dense silver particles in their cytoplasm showed focal or partial loss of granule contents, suggesting piecemeal degranulation (Fig. 2). Mast cells around free silver particles also showed piecemeal degranulation. These activated mast cells probably contributed to the development of pruritus and inflammatory reaction in the present case.

A case of anti-p200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita.

SIR, Anti-p200 pemphigoid is a new disease entity, which was first described in 1996 by Hashimoto’s group. They described an unusual case with autoimmune subepidermal bullous lesions that clinically resembled bullous pemphigoid and a case with psoriasis vulgaris that developed extensive blister formation. Both the nonpsoriatic patient and the psoriatic patient were characterized by immunoglobulin (Ig)G autoantibodies against a novel 200-kDa lower lamina lucida component. To date, anti-p200 pemphigoid has been shown to present various clinical features. This new autoimmune bullous disease seems to be classified into three clinical forms: (i) coexistence with psoriasis, (ii) presenting the clinical features of vesicular pemphigoid, and (iii) presenting clinically atypical blistering features. In this report, we describe a new patient with anti-p200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita (EBA). A 28-year-old Japanese male was referred to us because of numerous pruritic bullous skin lesions on the entire body of 2 weeks’ duration. Neither he nor his family had a past history of psoriasis. On physical examination, large, tense bullae and vesicles with erythema, and erosions similar to the skin lesions of bullous pemphigoid were found on his entire body (Fig. 1). The blisters tended to form in an annular arrangement resembling linear IgA bullous dermatosis or dermatitis herpetiformis. Oral and genital mucosae were not involved. Laboratory examinations revealed marked leukocytosis (21Æ8 · 10 L mm) and eosinophilia (37%). Because of the severe skin lesions, systemic prednisolone 100 mg daily was commenced; the dose was tapered down to 60 mg daily within 1 week. Because new blisters still appeared, the patient was treated with the combination therapy of prednisolone 60 mg and azathioprine 100 mg daily. Subsequently, no new bullae developed. The lesions healed, leaving mild scarring or milia formation. The prednisolone and azathioprine were gradually tapered down to 12Æ5 mg and 50 mg daily, respectively, and maintained at that dosage thereafter. Histology of lesional skin taken during the acute phase showed subepidermal blistering with abundant neutrophils, eosinophils and fibrin. Lymphocytes and eosinophils were found in the upper dermis. Direct immunofluorescence showed linear deposits of IgG and C3 at the dermo–epidermal junction. Indirect immunofluorescence using normal human skin sections as a substrate showed circulating IgG autoantibodies against the basement membrane zone (> 1 : 160), which were reactive exclusively with dermal side of 1 mol L NaCl-split human skin (> 1 : 40). Immunoblotting with epidermal and dermal extracts of normal human skin was performed using methods described elsewhere. The patient’s serum reacted with a 200-kDa protein of dermal extract (Fig. 2). The 290-kDa EBA antigen was not detected. Autoimmune subepidermal blistering disorders include bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, linear IgA bullous dermatosis, cicatricial pemphigoid, anti-p200 pemphigoid, anti-p105 pemphigoid, autoanti-p450 pemphigoid, EBA and bullous systemic lupus erythematosus. Anti-p200 pemphigoid has been identified as a new distinct entity and named by Zillikens et al. They identified IgG autoantibodies against a novel 200-kDa lower lamina lucida target antigen in nonpsoriatic bullous disease and a patient with coexisting bullous skin disease and psoriasis. They also described a predominance of neutrophils in the dermal infiltrate in the histology. Several other basement membrane zone components have been suggested as target antigens of autoimmune bullous dermatoses; however, the 200-kDa autoantigen seems to be different from laminins 1, 5 and 6, and type VII collagen. It has not been clearly suggested

Multiple lesions of granuloma annulare following BCG vaccination: case report and review of the literature

A 12‐year‐old Japanese boy presented with asymptomatic, multiple annular, erythematous, infiltrated lesions on his left upper arm and right knee as well as the lateral side of the right ankle joint. He had noted these erythematous lesions five days after bacille Calmette‐Guerin (BCG) vaccination. The lesions gradually enlarged and increased in number. Topical corticosteroid therapy for several weeks failed to improve the lesions. There was no familial history of pulmonary tuberculosis.

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

Vasoactive intestinal peptide and inflammatory cytokines enhance vascular endothelial growth factor production from epidermal keratinocytes.

Background  Overexpression of vascular endothelial growth factor (VEGF) in epidermal lesions of psoriasis is well documented; however, its underlying mechanisms are largely unknown. We have recently demonstrated that vasoactive intestinal peptide (VIP) induces the production of cytokines such as interleukin‐6 and stem cell factor from keratinocytes, thereby contributing to the development of inflammatory dermatoses such as psoriasis.

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.

Activation of mast cells within a tumor of angiosarcoma: ultrastructural study of five cases.

The accumulation of mast cells around tumors is a well‐recognized phenomenon in a number of malignancies, including basal cell carcinoma, melanoma, and breast cancer. However, little information exists regarding mast cells within tumor nests. To clarify the role of mast cells infiltrating in skin cancers, we examined the morphological features of mast cells within tumors of five cases of angiosarcoma, including two patients with Stewart‐Treves syndrome, by electron microscopy. In light microscopy, mast cells were observed within tumor nests at various densities and exhibited weak staining intensity with toluidine blue. By electron microscopy, most of the tumor‐infiltrating mast cells exhibited anaphylactic or piecemeal degranulation, indicating that the mast cells had been activated in situ. Some mast cells were noted in close apposition to tumor cells, suggesting the existence of direct cell‐to‐cell interactions. Tumor cells adjacent to mast cells showed no degenerative changes. In conclusion, these results suggest that careful histologic examination in combination with electron microscopy should enable us to identify more mast cells within cancer lesions with greater sensitivity than in a number of prior reports. Furthermore, the close proximity of mast cells and surrounding tumor cells suggests some biologically significant role of mast cells in the development of angiosarcoma, including tumor growth as well as host immunity and stromal reaction.

Recalcitrant pemphigus foliaceus with Kaposi’s varicelliform eruption: report of a fatal case

An 88-year-old man presented with a 10-day history of erosive skin lesions on the trunk. On physical examination, multiple erythematous areas and erosions with flaccid bullae were found on the trunk and upper limbs. The oral mucosa was not involved. History of recurrent herpes simplex labialis or genitalis was uncertain. Histology showed subcorneal blisters with acantholytic keratinocytes in the upper epidermis. Direct immunofluorescence revealed IgG and C3 on the intercellular spaces of the epidermis. IgG antidesmoglein (Dsg)1 antibody was 960 (cut-off value 1⁄4 14), but antiDsg3 antibody was not detected in the patient s serum by ELISA (cut-off value 1⁄4 7). A diagnosis of pemphigus foliaceus (PF) was made, and the patient admitted to hospital. A regimen of oral prednisolone 40 mg daily was begun, but this did not control the skin lesions. Prednisolone was increased to a 100 mg and combined with azathioprine 100 mg daily. On the day after hospital admission, denuded areas which caused a severe burning sensation, appeared on the buttocks and trunk. The patient was febrile (37.8 C). Cutaneous examination revealed umbilicated vesicles and bullae widely disseminated and coalesced into large ulcers over the entire trunk (Fig. 1). Additionally, numerous, discrete, crusted ulcerative lesions appeared on the face (Fig. 2). Laboratory tests revealed raised liver enzymes including serum aspartate aminotransferase 1138 mU ⁄ mL (normal 5–43) and alanine aminotransferase 890 mU ⁄ mL (5–60), suggesting possible herpes hepatitis. IgG anti-Dsg1 ELISA index was increased to 1640, although anti-Dsg3 antibody was not detectable. Serum herpes simplex virus (HSV) antibodies IgG and IgM were measured by ELISA as > 128 (index) and 13.9 (positive), respectively. This suggested reactivation of HSV rather than an initial infection. Kaposi s varicelliform eruption was diagnosed and intravenous aciclovir was administered. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were also PD