[Cyclosporin in the treatment of bullous pemphigoid: preliminary study]. / La ciclosporine dans le traitement de la pemphigoïde bulleuse: étude préliminaire.

Bullous pemphigoid is a typical autoimmune disease. It is classically treated with systemic corticosteroids alone or combined with immunosuppressants. Cyclosporine A (CyA), a new immunosuppressive agent with high activity in organs and bone marrow transplantation, could be expected to prove effective in this disease owing to its action on lymphocytes. Seven patients with bullous pemphigoid were treated with CyA in daily doses of 6 to 8 mg/kg bodyweight. Treatment was monitored by measurements of serum CyA, creatinine and liver enzyme levels. The effectiveness of treatment was assessed on clinical changes. The seven cases are dealt with individually, with a brief case-report for each of them. The only side-effects observed were reversible rises in serum creatinine levels and hypertrichosis in two cases; these are usual reactions to the drug. Hormonal assays were normal in two female patients. Concerning results, our patients fell into two groups. Among those treated with CyA alone there were two failures and two sustained satisfactory results. Treatment was successful in all patients treated with CyA during relapses under corticosteroid therapy, but two patients relapsed after CyA was discontinued. It is concluded that CyA is of no interest in the acute phase of bullous pemphigoid, that the long-term stability of the results obtained is doubtful and that this potentially nephrotoxic drug should be avoided or administered with extreme caution in elderly people, since their renal function may be at the limit of normality.

Alpha interferon treatment in atopic dermatitis.

Eight patients suffering from atopic dermatitis were treated with interferon alpha 2b. They received low or intermediate doses (9-15 x 10(6) U/week) for a short period of time (4-8 weeks), with a moderate improvement of skin lesions in 4 of them and no change or an exacerbation of the disease in the other 4. Among the 4 patients who slightly improved at 4 weeks, 3 did not show any beneficial effect of interferon after 8 weeks. Serum IgE levels, which were increased in all patients before treatment, were not reduced under interferon therapy. This study shows that intermediate doses of interferon alpha 2b are not effective in the short-term treatment of atopic dermatitis.

[Generation of cytotoxic lymphocytes in lympho-epidermal mixed cultures in man]. / Génération de lymphocytes cytotoxiques en cultures mixtes lympho-épidermiques chez l'homme.

The ability of human normal skin epidermal cells (EC) to induce the generation of alloreactive cytotoxic T lymphocytes (CTL) was investigated in vitro using the Mixed Skin Cell lymphocyte Reaction (MSLR) model. In human MSLR, EC stimulated the proliferation of allogeneic peripheral blood lymphocytes (L) as measured, after 6 days, by 3H-thymidine uptake. In parallel, the generation of alloreactive CTL was tested in 18 hr 51CR release assays against L targets (targets autologous to EC that stimulated in MSLR). Allogeneic, not autologous MSLR, lead to the generation of CTL; alloreactive CTL were not generated against targets allogeneic to stimulating EC; no CTL activity occurred without previous stimulation by EC. These data indicate that in vitro MSLR may provide an useful tool for the investigation of lympho-epidermal interactions in man and our understanding of lymphocytotoxicity mechanisms that occur in vivo in response and/or directed to epidermal constituents .

Treatment of cutaneous T cell lymphoma with intermediate doses of interferon alpha 2a.

In this study we treated 6 patients with epidermotropic cutaneous T cell lymphoma (CTCL) with intermediate doses of recombinant alpha 2a interferon (18-100 x 10(6) IU/week) for 2-6 months. One patient experienced complete clinical remission in spite of a persistent dense lymphocytic skin infiltrate. One patient was markedly improved and 2 patients were moderately improved. The clinical condition of the 2 remaining patients was unchanged by interferon treatment. In all cases lesions relapsed a few weeks after treatment was discontinued. This study shows that interferon can be used to treat epidermotropic CTCL. However, a 2- to 6-month treatment using moderate doses did not lead to the high percentage of remission previously reported by others with high doses of recombinant alpha 2a interferon, for longer periods. This result suggests that interferon should be used at high doses and/or for long time periods for clinical improvement of CTCL patients.

Nickel release from stainless steels.

In 1994, a study of nickel release and allergic contact dermatitis from nickel-plated metals and stainless steels was published in this journal. It was shown that low-sulfur stainless steel grades like AISI 304, 316L or 430 (S < or = 0.007%) release less than 0.03 microgram/cm2/week of nickel in acid artificial sweat and elicit no reactions in patients already sensitized to nickel. In contrast, nickel-plated samples release around 100 micrograms/cm2/week of Ni and high-sulfur stainless steel (AISI 303-S approximately 0.3%) releases about 1.5 micrograms/cm2/week in this acid artificial sweat. Applied on patients sensitized to nickel, these metals elicit positive reactions in 96% and 14%, respectively, of the patients. The main conclusion was that low-sulfur stainless steels like AISI 304, 316L or 430, even when containing Ni, should not elicit nickel contact dermatitis, while metals having a mean corrosion resistance like a high-sulfur stainless steel (AISI 303) or nickel-plated steel should be avoided. The determining characteristic was in fact the corrosion resistance in chloride media, which, for stainless steels, is connected, among other factors, to the sulfur content. Thus, a question remained concerning the grades with an intermediate sulfur content, around 0.03%, which were not studied. They are the object of the study presented in this paper. 3 tests were performed: leaching experiments, dimethylglyoxime and HNO3 spot tests, and clinical patch tests; however, only stainless steels were tested: a low-sulfur AISI 304 and AISI 303 as references and 3 grades with a sulfur content around 0.03%: AISI 304L, AISI 304L added with Ca, AISI 304L+Cu. Leaching experiments showed that the 4 non-resulfurised grades released less than 0.5 microgram/cm2/week in acid sweat while the reulfurized AISI 303 released around or more than 0.5 microgram/cm2/week. This is explained by the poorer corrosion resistance of the resulfurized grade. Yet all these grades had the same reaction to the DMG test (negative result), which shows again its lack of sensitivity. In contrast, the HNO3 spot test distinguished AISI 303 from the non-resulfurized grades. Clinical patch tests again showed that some patients (4%) were intolerant to AISI 303, while none were intolerant to the other grades. Thus, this study confirms that non-resulfurized stainless steels (S < or = 0.03%) like Ni-containing 304 and 304L should not elicit Ni contact dermatitis, while the resulfurized grades (S > 0.1%) should be avoided.

Clinical evaluation of topical isotretinoin in the treatment of actinic keratoses.

BACKGROUND: Retinoids have been shown to improve the manifestations of skin photodamage, including actinic keratoses. OBJECTIVE: The efficacy and tolerability of isotretinoin 0.1% cream in the treatment of actinic keratoses were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study. METHODS: One hundred patients were randomly assigned to treatment with 0.1% cream or vehicle twice daily for 24 weeks to the face, the scalp, and the upper extremities. Patients were assessed every 4 weeks by the investigators, who counted and recorded the number of lesions in each treatment area. The 93 patients who had at least one postbaseline assessment were included for efficacy analysis. Local tolerability was evaluated at each study visit. RESULTS: On the face, the reduction in number of actinic keratoses (mean +/- SEM) at the end of treatment was greater for patients treated with isotretinoin (3.9 +/- 0.6, i.e., 66% of patients with a reduction > 30%) than with placebo (1.7 +/- 0.5, i.e., 45% of patients with a reduction > 30%); this difference was statistically significant (p = 0.001). No significant drug effect was seen for lesions on the scalp or upper extremities. Mild to moderate local reactions with isotretinoin abated with reduced treatment frequency. CONCLUSION: Our results suggest that isotretinoin 0.1% cream cannot compete with more rapid treatments of actinic keratoses. However, its effect on facial lesions may be beneficial during long-term treatment of associated sun-damaged skin.

Role of HLA-DR bearing Langerhans and epidermal indeterminate cells in the in vitro generation of alloreactive cytotoxic T cells in man.

Human epidermal cells (EC) act as stimulator cells in the mixed-skin cell lymphocyte culture reaction (MSLR). To analyze the role of human epidermal Langerhans cells (LC) and indeterminate cells (IC), which are the only cells expressing the DR-Ia-like antigens in normal epidermis, in the generation of alloreactive cytotoxic T lymphocytes (CTL) in cell-mediated cytolysis, 18-hr 51Cr-release assays against PBL targets (targets autologous to stimulator EC) were conducted after allogeneic human MSLR. MSLR and CTL assays were conducted with, as stimulator cells, suspensions of normal human EC as controls, and EC after: (1) preincubation with anti-HLA-DR or OKT6 (specific for LC in EC suspension) monoclonal antibodies; (2) panning, a monolayer technique used to deplete EC suspensions in OKT6 or DR-positive cells. The generation of alloreactive CTL was found to occur only after allogeneic MSLR and when targets and stimulator cells were from the same donor; it was reduced by EC incubation: cytotoxic activity 26.66 +/- 3.84 (controls); 8.8 +/- 3.6 and 7.7 +/- 3.7 (EC incubated with OKT6 or anti-DR, respectively); it was reduced or abolished when the EC used in MSLR were depleted in OKT6 or DR-positive cells by panning. These findings demonstrate that human LC and IC are necessary for an optimal in vitro sensitization in MSLR and the subsequent in vitro generation of alloreactive CTL in man.

In vitro studies of epidermal antigen-presenting cells. The mixed skin lymphocyte reaction: an in vitro model for the generation of alloreactive cytotoxic T cells by human epidermal cells.

Langerhans cells and indeterminate cells are the unique antigen-presenting epidermal cells participating in human lympho-epidermal interactions. They bear class II HLA-DR molecules, can substitute for macrophages in antigen presentation, induce a T-cell proliferative response to antigens and haptens in sensitized donors, and are necessary for alloantigen T-cell activation and generation of alloreactive cytotoxic T cells in vitro. Indirect immunofluorescence and immunogold electron microscopy on class II positive epidermal cell enriched suspensions (panning, FACS) indicated two populations of DR-positive epidermal cells: strongly DR-positive cells (25-30, 8% of positive epidermal cells) and faintly DR-positive cells, with a density of surface DR sites of respectively 5 X 10(5) and 1 X 10(5). Most Langerhans cells are among this second group while indeterminate cells are usually strongly DR-positive. OKT6-labelled cells were only typical Langerhans cells.

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.