IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.

Eosinophil cationic protein (ECP), one of the eosinophil granule proteins, is released during allergic reactions. We investigated the possibility of correlations among the serum levels of ECP, clinical activity, and eosinophil number in patients with atopic dermatitis (AD). Forty-four patients with AD and 25 normal, non-atopic subjects were studied. ECP was quantitated by a double antibody radioimmunoassay. The levels of serum ECP correlate with the grading of severity of clinical evaluations in AD. The patients with severe and moderate AD had significantly higher ECP concentrations than normal controls (p less than 0.001); mild AD had levels identical with those of control groups. A positive correlation was observed between the number of peripheral blood eosinophils and serum ECP levels in the severe cases (r = 0.67, p less than 0.05). Furthermore, these ECP levels significantly decreased in response to either improvement of clinical severity of AD or decreased numbers of blood hypodense eosinophils in anti-allergic drug-treated patients. No coefficient of correlation was observed between serum ECP and IgE levels. These findings indicate that eosinophils may release their granular contents, including ECP, into the peripheral circulation and/or inflammatory skin lesions and subsequently provoke a clinical exacerbation by stimulating allergic reactions.

Eosinophil phenotypes were investigated in peripheral blood and skin lesions from eight patients with bullous pemphigoid (BP). By Nycodenz density gradients fractionation, blood eosinophils were divided into two phenotypes; normodense (greater than 1.080 g/ml) and hypodense (less than or equal to 1.080 g/ml). Increased numbers of hypodense eosinophils were observed in the blood from all patients with BP. Immunocytochemical observations, using an EG2 monoclonal antibody to react with the secretion form of eosinophil cationic protein (ECP), revealed that EG2 was expressed in 86 +/- 3% of hypodense phenotypes and 3 +/- 2% of normodense phenotypes. Ultrastructurally, hypodense eosinophils were characterized by numerous spheroidal granules, each with a lytic crystalloid core. These indicate that the hypodense phenotype represents a cell in an activated state. Only eosinophils with immunocytochemical and morphological characteristics similar to hypodense phenotypes infiltrated around the basement membrane zone in involved skin of BP. Furthermore, direct adherence of eosinophils associated with degranulation into basal keratinocytes was seen at the sites of blistering lesions. Bullous fluids contained higher concentrations of ECP than sera as determined by a radioimmunosorbent assay; thus hypodense (activated) eosinophils may directly damage the basal keratinocytes by releasing their granule proteins, subsequently leading to dermo-epidermal separation.

A 62‐year‐old Japanese man had visited Rondonia in central Brazii on May 28, 1994, at which time he suffered insect bites on the left axiila and ieft chest regions. Three bites persisted and became tender and painfui. These areas developed into tender nodules with moderate serous drainage from a central pore. Malaise and an intermediate‐grade fever accompanied the eruption. The tender nodules continued after he returned to Japan on July 7. The diagnosis of furunculosis was made by his family physician, but treatment with oral cefdinir (300 mg per day) and naproxen (600 mg per day) for 2 days and application of ointment containing 0.1% gentamicin sulfate failed to resolve the lesions. The patient complained of a crawling sensation under the skin. Since a maggot was removed from the axillary lesion with the aid of the patient's fingers, he was referred to the Dermatology Clinic of the Kurume University Hospital on August 1, for evaluation of parasitic diseases. Physical examination revealed two firm furuncle‐like erythematous nodules, 2.0 cm in diameter, with a centrally placed 4 mm punctum on the left side of the chest (Fig. 1). There was serous drainage from each punctum and a motile larva was seen in each cavity. A lesion on the axilla had healed spontaneously. Laboratory tests were normal. Two florid lesions on the chest were surgically removed under local anesthesia with 0.5% lidocaine hydrochloride. Histologic examination revealed a mixed cell inflammatory infiltrate throughout the dermis with a tract containing a larva. Examination of the larva revealed a segmented ovoid organism, 1.5 × 0.5 cm in size (Fig. 2). The lesions healed completely within 2 weeks without further treatment. The larva removed by the patient was forwarded to the Department of Medical Zoology, Faculty of Medicine, Tokyo Medical and Dental University, and was identified as third instar larvae of Dermatobia hominis, the human botfly. The other two of the third instar larvae were transplanted under the skin of a rat and a mouse to obtain pupae or adults, but they failed to pupate and died.

We report three cases of pigmentary demarcation lines associated with pregnancy. In addition, we reviewed 19 cases including our 3 cases, which were reported in Japan. Most cases occurred during the latter period of pregnancy (after the seventh month), and the pigmentation faded spontaneously or disappeared a few months after delivery in all cases except one. Pigmentary demarcation lines are classified into five groups (types A-E). Of the 19 cases we reviewed, 2 cases showed lines of both types A and B, whereas all the other cases showed type B lines. Although there have only been 29 cases of pigmentary demarcation lines associated with pregnancy reported to date, before ours, we experienced 3 cases within 3 months, therefore it is possible that many such cases are overlooked. Pigmentary demarcation lines are mainly a cosmetic problem. Two of our three cases presented to obstetricians initially. We suggest that dermatologists should be aware that pigmentary demarcation lines may be associated with pregnancy.