Linear IgA bullous dermatosis of childhood with autoantibodies to a 230 kDa epidermal antigen.

Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease defined on the basis of direct immunofluorescence findings. However, more recent techniques used to study bullous dermatoses suggest that LABD may be heterogeneous. A patient with LABD of childhood (chronic benign disease of childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. This young girl's periorificial (mouth, genitalia), erythematovesicular lesions were diagnosed initially as herpes simplex. Histologic examination revealed eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA autoantibodies that reacted with the epidermal side of salt-split skin; these reacted by Western blot with a 230 kDa epidermal antigen, as in bullous pemphigoid. This case, fulfilling the diagnostic clinical and direct immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.

[Acanthosis nigricans, hyperandrogenism, insulin resistance and mixed hyperlipemia]. / Acanthosis nigricans, hyperandrogénie, insulinorésistance et hyperlipémie mixte.

We report the case of a 22-year old woman who presented skin lesions of acanthosis nigricans, hirsutism and secondary amenorrhoea. She had high plasma levels of adrenal androgens and low plasma levels of sex steroid binding protein. Polycystic ovaries were discovered in the course of a laparotomy performed for paraovarian cyst. An oral glucose tolerance test revealed a state of hyperinsulinism with intolerance to carbohydrates, while the body mass index was normal. This insulin resistant state corresponded in vitro to a decrease in the number of erythrocyte insulin receptors without decrease in their affinity for insulin. Following paradoxical improvement during a full-term pregnancy, there was gradual deterioration of diabetes control requiring insulin therapy. This metabolic decompensation was accompanied by major hyperlipaemia followed by acute haemorrhagic pancreatitis. This case illustrates the course of a type A insulin resistance syndrome which was detected at an early stage in front of an hirsutism-acanthosis nigricans association. The underlying pathogenic mechanisms of these pathologies are discussed.

Treatment of nine cases of pemphigus vulgaris with cyclosporine.

The effects of cyclosporine were studied in nine patients suffering from pemphigus vulgaris. Of four patients treated with cyclosporine alone, only one cleared. Of four corticosteroid-resistant pemphigus vulgaris patients, all improved after cyclosporine addition to corticosteroids. The last patient treated from the beginning with a combined treatment (cyclosporine-corticosteroids) did not respond. The main advantage of using cyclosporine is to allow a decrease in corticosteroid dosages and to permit treating corticosteroid-resistant pemphigus vulgaris patients. No detectable irreversible side effects were noted. The treatment was discontinued in two patients because of reversible side effects. Cyclosporine alone does not seem to be an adequate treatment of the acute phase of pemphigus vulgaris but could be used in addition to corticosteroids. The most important drawback of cyclosporine treatment is the occurrence of clinically silent renal dysfunction (tubular involvement and interstitial fibrosis), which may occur during long-term treatments. More studies need to be carried out to determine the effects of low doses of cyclosporine on renal function in patients who have normal renal functions.

[Severe psoriasis induced by chloroquine (nivaquine)]. / Psoriasis grave induit par la chloroquine (nivaquine).

The adverse effects of a variety of drugs on psoriasis are well documented, and they generally result in aggravation of the disease. We report the case of a 75-year old man who developed a psoriatic erythroderma and a generalized pustular psoriasis two weeks after the beginning of an antimalarial treatment. The psoriasis responded poorly to etretinate alone, and an etretinate-methotrexate combination was needed to cure the patient. Some psoriasis vulgaris plaques persisted for six months after the acute complication. Thus, chloroquine should be entered in the list of drugs which may induce psoriasis.

[Kaposi angiosarcoma in renal transplant recipients]. / L'angiosarcome de Kaposi chez les transplantés rénaux.

Four cases of Kaposi's sarcoma in recipients of renal transplants are reported. The 4 patients of Italian origin were male. Kaposi's sarcoma, began during pre-transplantation haemodialysis, then extended in one of the patients; in the remaining 3 patients it developed 20 months on average after transplantation. All patients were receiving an immunosuppressive treatment (azathioprine, systemic corticosteroids, anti-lymphocyte serum). Kaposi's sarcoma was located in the skin and mucosae, sometimes in lymph nodes and viscera. In 2 patients the cutaneous and mucosal lesions responded well to vindesine: in the other two patients withdrawal of the immunosuppressive therapy had no effect on the course of the disease. This study highlights the multiple factors involved in the development of Kaposi's sarcoma, notably immunosuppression and the ethnic factor.

Reactivity of anti-HLA class I polymorphic monoclonal antibodies with normal human skin.

In this work the reactivity of 16 monoclonal antibodies raised against different HLA class I specificities was tested with human skin of healthy donors of known HLA typing. By indirect immunofluorescence, six antibodies reacted strongly with keratinocytes carrying the corresponding alloantigens. The reactivity of 3 other antibodies which was weak or absent using indirect immunofluorescence, was enhanced by various amplification systems such as avidin-biotin-peroxidase method, biotin-streptavidin-fluorescein complex and especially preliminary trypsin treatment that revealed alloantigens masked in the epidermis. The immunostaining of 4 antibodies was negative regardless of the method used. Some of the antibodies we tested cross-reacted with cytoplasmic antigens of keratinocytes. This study has allowed to select a battery of monoclonal antibodies which can specifically detect alloantigens on keratinocytes and will be useful for the recognition the cell origin in allografting experiments.

Growth and differentiation of human epidermal cultures used as auto- and allografts in humans.

Human keratinocytes from small skin specimens were grown on mouse 3T3 cell feeder layers into epidermal sheets free from Langerhans cells and MHC class II antigen. These were found to be suitable for the permanent coverage of wounds when used as autografts or allografts. We report here the ultrastructural differentiation of this cultured epidermis after grafting onto autologous or allogeneic recipients. The cultured epidermis was a thin but multilayered Malpighian epithelium composed of keratinocytes at different stages of differentiation. The dermo-epidermal basement membrane was newly synthesized during the first few days following transplantation onto de-epidermized wounds. The analysis of keratins and examination of various keratinocyte membrane antigens by immunofluorescence indicated that full terminal epithelial differentiation was only achieved after in vivo transplantation of the cultured epidermis. Langerhans cells, absent in cultures, progressively colonized the grafts, while melanocytes, not detectable in sections of the cultures, were identified among the keratinocytes 2 weeks after grafting.

Expression of class I-MHC antigens by cultured human epidermis and epidermal allografts.

In vitro grown class II-MHC antigen free epidermal sheets were used as epidermal allografts (EAG) across a major histocompatibility barrier in 20 non-immunosuppressed recipients suffering from leg ulcers. Class I antigens were expressed on cell membranes of basal cell layer only on the epidermal sheets. After grafting, patchy areas of membrane fluorescence were observed among cells from the suprabasal layers on the epidermis from skin biopsies taken between days 5 and 28. All cells of the basal and the suprabasal layers expressed class I antigens on biopsies taken after day 28, as on normal human epidermis. This work demonstrates that class I antigens are expressed by epidermal cells in cultures used for grafting. The absence of rejection cannot be explained by the absence of class I-MHC antigens in EAG.

Regressing atypical histiocytosis (of Flynn). Report of a new case.

Regressing atypical histiocytosis (of Flynn) is a recently described disease that, in spite of histological features of malignancy, seems to run an indolent clinical course. A new case of this rare condition is reported herein.

Effects of PUVA and mechlorethamine treatment of psoriatic patients on epidermal Langerhans' cells.

Using OKT6 monoclonal antibody, we investigated the number of epidermal Langerhans' cells (LCs) in involved skin from patients with psoriasis, before and after mechlorethamine (HN2) or PUVA treatment. The number of LCs remained at about pretreatment number during three weeks of HN2 treatment alone, though they were reduced after 10 systemic PUVA treatments. Therefore, in contrast to PUVA which influences LCs, HN2 seems to have little effect on LCs. LCs in psoriatic plaques were, in number, 3-4 times less numerous than those in uninvolved, nontreated epidermis.