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We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various-sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme-linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1-3 showed negative results. Immunoblotting using the full-length human Dsg1 recombinant protein showed a positive band. TEM examination showed various-sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation-regulated chemokine and interleukin-5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP.

Summary We report a patient with herpetiform pemphigus(HP)who showed reactivity only with pemphigus vulgaris(PV)antigen but not with pemphigus foliaceus(PF)antigen. Direct and indirect immuno- fluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid- separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV.in addition to PF, with unique clinical and histological features.

The clinicopathological features of 22 cases of the Dowling-Meara form of epidermolysis bullosa simplex (DM-EBS) (11 males, 11 females; aged 5 days-46 years) were reviewed using data collected over a 10-year period. All cases presented clinically within the first 5 days of life. Early blisters were often large (up to 5 cm in diameter), and were mostly acral and particularly periungual. Some cases presented with more widespread erosive skin changes, and two neonates with extensive skin involvement died as a result of overwhelming sepsis. After the neonatal period a different pattern of blistering occurred with more proximal haemorrhagic, herpetiform clusters of blisters. Central healing with recurrent blistering at the margins of these areas was frequently noted. Other physical signs included varying degrees of intra-oral blistering, nail shedding, nail dystrophy, minor scarring, palmo-plantar keratoderma, a lack of seasonal variation and improvement during later childhood. The underlying pathological mechanism in DM-EBS is basal cell cytolysis, or rarely acantholysis, in association with tonofilament (TF) clumping. TF clumping was found in lesional, perilesional and some non-lesional skin, suggesting that the tonofilament abnormality may be of primary aetiological significance in DM-EBS. TF clumping may be due to specific keratin abnormalities because the altered TF were found in a distribution similar to the known distribution of the basal cell keratins, K5 and K14. The level of blistering was invariably very low within the epidermal basal layer and often less than 0.5 microns above the basement membrane. We conclude that DM-EBS is a distinct, and probably under-recognized genodermatosis which tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period, when it may be confused with junctional or severe recessive dystrophic EB. Electron microscopy is the best means for demonstrating the characteristics cytoskeletal disorder and confirming the diagnosis.

We report a 6-year-old boy suffering from acquired epidermolysis bullosa, who presented with extensive lesions of the mucous membranes and disseminated, herpetiform and 'cluster of jewels'-like vesicles and bullae arising on erythematous plaques. Direct immunofluorescence showed linear deposits of IgG and C3 at the epidermal basement membrane zone. Indirect immunofluorescence demonstrated circulating autoantibodies (titre 1:128-1:256) directed at the blister floor of human NaCl-split skin, and reacting specifically with collagen VII of the anchoring fibrils, as demonstrated by immunoblotting. The disease was controlled with a combination of dapsone and prednisone. This case demonstrates the importance of modern immunological techniques in classifying childhood autoimmune bullous diseases, as precise diagnosis is important in determining an appropriate therapeutic regimen.

The possibility that viruses are involved in the pathogenesis of aphthous lesions was investigated. Immunofluorescent-antibody tests showed that antigens of adenovirus and herpesvirus are present in cells from aphthous lesions and lymphocytes from persons with aphthae more frequently than in cells from normal persons. Antigens of adenovirus type 1 and herpesvirus caused blastogenic transformation in a significant proportion of lymphocytes from aphthous patients. The findings suggest that virus-carrier lymphocytes may be an important factor in the development of certain viral diseases. The pathogenesis of recurrent aphthae is not well understood. Adenovirus type 1 was isolated from two patients with herpetiform ulceration sec. Cook [1]. Antigens of adenovirus and herpesvirus could be detected by the immunofluorescent technique in the cells of scrapings from aphthae of these two patients [2]. We now report experiments carried out with a larger group of patients in which the incidence of viral antigens in the cells of aphthous scrapings was determined. Since the cellular infiltrations of recurrent oral ulcers consist mostly of lymphocytes [3, 4], the presence of antigens of adenovirus and herpesvirus in the circulating lymphocytes of aphthous patients and of control persons, who never suffered from this illness, was studied. By means of a lymphocyte-transformation test [5], a procedure which can be performed in vitro, the sensitivity of the lymphocytes from aphthous patients against antigens of adenovirus and herpesvirus was tested.