Th. van Joost

Low‐dose cyclosporin A in severe psoriasis. A double‐blind study

Twenty patients with severe plaque psoriasis were selected to receive either low‐dose cyclosporin A (CyA) or placebo (CyA vehicle) in a double‐blind randomized trial at two centres.

Short-term use of cyclosporin A in severe psoriasis

The effectiveness of cyclosporin A (CyA) in low dosages (mean 5 mg/kg/day) for short‐term treatment of severe psoriasis was studied. Of five patients with severe progressive psoriasis vulgaris (mean PASI score 43.8), an almost complete remission in three patients, and a large reduction in PASI score in the remaining two patients, was obtained within 4 weeks. No important clinical side‐effects were found but there was biochemical evidence of slight renal dysfunction in one patient. The mean percentage reduction in the PASI score was 84%. It was concluded that the results reported justify further study of the use of CyA in the treatment of severe psoriasis.

Oral manifestations of gold allergy

BACKGROUND Sensitization to gold in a large group of patients suspected of clinical allergy to this metal has not been reported. OBJECTIVE Two hundred patients with symptoms of persistent oral mucosal or cutaneous lesions that were possibly related to allergy to constituents of gold alloys or gold jewelry were patch tested to determine the frequency of sensitization. METHODS Patch testing was performed with the European standard series and a series of dental materials including three different salts of gold. A persistent papular reaction to gold-(tri)chloride was considered a positive reaction. RESULTS In 17 patients (8.5%, all women, mean age 50.2 years) persistent papular patch test reactions to both 0.5% and 1.0% gold(tri)chloride were observed. In five of seven patients with oral lichen planus (OLP) and in one of six patients with the burning mouth syndrome, gold in the dentures was replaced. Particularly in patients with OLP, a significant but variable improvement was observed. In all cases in which gold was replaced and improvement occurred, the patients were sensitized to 0.5% gold(tri)chloride. One patient with allergic contact stomatitis and one patient with allergic contact dermatitis healed completely after gold had been replaced. CONCLUSION Sensitization to gold should be considered as a possible cause of allergic contact dermatitis and allergic contact stomatitis as well as a pathogenic or triggering factor in OLP.

In vivo cytokine profiles in allergic and irritant contact dermatitis.

Local cytokine profiles in skin biopsies from allergic and irritant patch test reactions were determined by in vivo immunohistochemistry to differentiate between these 2 clinically identical afflictions especially at the time of final reading in diagnostic patch testing. Biopsies were taken from established allergic persons after specific allergic patch test.‐, to epoxy resin (1%) and formaldehyde (1%) and from non‐allergic individuals with irritant patch tests to sodium lauryl sulfate (10%) and formaldehyde (8%). At 72 h after application of the agents, significantly enhanced frequencies of dermal infiltrating cells, producing IL‐1α, TNF‐α. IL‐2. and IFN‐γ per 100 infiltrating cells in the dermis. were observed in allergic as well us irritant patch test reactions, as compared to normal skin. Significantly higher frequencies of IL‐ Iα‐producing cells were observed in biopsies from epoxy resin (1%) allergen‐affected and sodium lauryl sulfate (10%) irritant‐affected skin as compared to formaldehyde (1%) allergen‐affected skin. In addition, significantly higher frequencies of TNF ‐α reproducing cells were observed in epoxy resin allergen‐affected skin us compared to Formaldehyde (1%) allergen‐affected and formaldehyde (8%) irritant affected skin. The allergic and irritant patch test reactions showed similar levels of expression of the Thl cytokines IL‐2 and IFN‐γ in the dermis. confirmed by probe based detection of IL‐2 mRNA and IFN‐γ‐ mRNA, In conclusion, the described similarity shows that allergens and irritants can induce the same profile of IL‐la. TNF‐α. IL‐2. and IFN‐γ production, resulting in the near impossibility of discriminating between allergic and irritant contact dermal is at the lime of patch test reading.

Cyclosporine in atopic dermatitis:Modulation in the expression of immunologic markers in lesional skin

BACKGROUND In previous studies, oral cyclosporine was highly effective in the treatment of patients with severe atopic dermatitis. In this study seven patients with severe and therapy-resistant atopic dermatitis underwent therapy with cyclosporine, 5 mg/kg/day, for 6 weeks. OBJECTIVE The effect of cyclosporine on the expression of cytokines, which probably play a role in this disease, was examined. METHODS The study was performed with a panel of antibodies as markers of inflammatory cells, adhesion molecules, and cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor-alpha [TNF-alpha] and interleukins 1 alpha, 1 beta, and 8 [IL-1 alpha, IL-1 beta, and IL-8, respectively]). They were visualized by indirect immunoperoxidase techniques. RESULTS After 2 weeks of cyclosporine therapy, a reduction of 60% in the disease (severity and extent) was observed. This reduction was 89% after 4 weeks and 90% after 6 weeks of therapy. Results of indirect immunoperoxidase stains performed on lesional skin sections after 2 weeks of treatment showed statistically significant reduced numbers of CD14+, CD25 (IL-2R+) and IL-8+ inflammatory cells in the dermis and CD36(OKM5)+ cells in both the epidermis and dermis. The number of cells expressing IFN-gamma and TNF-alpha, assumed to be the products of the helper T-cell (TH)1 subset, was unaltered despite the impressive clinical benefit observed. Keratinocytes in lesional atopic skin did not express intercellular adhesion molecule type 1 (ICAM-1). The expression of the adhesion molecules ICAM-1, lymphocyte function-associated (LFA) type 1, and LFA-3 on inflammatory cells also remained unaffected by cyclosporine treatment. CONCLUSION A statistically significant reduction in the number of activated T cells and in the number of cells expressing the IL-2 receptor (CD25) paralleled a marked improvement in the disease and supports the view that atopic dermatitis is based on a T-cell-mediated immune inflammation.

Contact stomatitis and dermatitis to nickel and palladium

17 subjects were tested epicutaneously with 22 materials, including Ni, Pd, Cr and Co. 5 subjects with a positive allergic skin reaction to Ni were tested with a pure metallic nickel plate 3 × 5 mm, which was attached to the buccal side of one lower premolar. These 5 subjects all developed local allergic contact stomatitis on the mucosa of the cheek adjacent to the metal plate. This was confirmed histologically. The same oral test with pure metallic palladium gave no reaction in subjects with a positive patch test. A control group gave no reactions to the metal plates. Allergic contact stomatitis was diagnosed with the help of both clinical and histological examinations.

Primary cutaneous adenoid cystic carcinoma: case report, immunohistochemistry, and review of the literature

We report a case of primary cutaneous adenoid cystic carcinoma in a 75‐year‐old man. Electron microscopy revealed similar features to those previously described in adenoid cystic carcinomas of salivary gland origin: wide intercellular spaces, pseudocysts containing replicated basement membrane‐like material and true lumina lined by cytoplasmic membranes with numerous microvilli. Immunohistochemistry using antibodies to several cytoskeletal proteins (keratins and actin) indicated the presence of two epithelial tumour cell populations, one with the phenotype of myoepithelial cells, lining the pseudocysts and the periphery of the tumour fields, and another with the phenotype of acinar cells of the secretory coil of sweat glands. In addition, the tumour showed immunoreactivity for epithelial membrane antigen, but not carcinoembryonic antigen. A review of the literature on other cases of primary cutaneous adenoid cystic carcinoma showed that this tumour generally affects older patients with a female to male ratio of 4:1. The most common tumour site appears to be the scalp (40%), and the recurrence rate is 50%. Surgical treatment with extensive resection margins is recommended.

Contact allergy to denture materials in the burning mouth syndrome.

Several factors may be responsible for stomatitis in general and the burning mouth syndrome in particular. The results of patch testing are reported in 4 patients with burning mouth symptoms thought to be due to sensitization to denture material. 2 patients reacted to substances in Luxene® dentures, but the allergens were not identified. In a 3rd patient, sensitization was found to monomeric methyl methacrylate. The other patient gave positive patch tests to epoxy resin (and bisphenol A), probably present in glue used for repair of dental plates. To obtain a complete diagnosis in cases of suspected contact stomatitis due to allergens in dentures, a reliable standard test series is required.

Effects of cyclosporine on cytokines and cytokine receptors in psoriasis

Abstract Background: Oral cyclosporine is effective in the treatment of recalcitrant psoriasis. However, the precise mechanism(s) are not fully understood. A possible mode of action may be via down-modulation of proinflammatory cytokines that are increased in psoriatic lesions. Objective: This study was designed to monitor the effects of cyclosporine treatment on the expression of cytokines, cytokine receptors, and other markers of inflammation in psoriatic skin. Methods: Ten patients with recalcitrant psoriasis were treated with cyclosporine. The in vivo effects of cyclosporine on cytokines and their receptors were studied by the use of cryostatcut sections and a panel of antibodies. The in vitro effects were studied with flow cytometry of epidermal cell suspensions prepared from psoriatic lesions and control skin. Results: Clinical improvement was noted in all patients after 2 weeks of cyclosporine treatment. The expression of interleukin-1β, interleukin-8, CD25(IL-2R), CD36 and E-selectin were significantly decreased, whereas the number of tumor necrosis factor-receptor-positive epidermal cells was significantly increased in psoriatic lesions. Conclusion: Clinical improvement of psoriasis with cyclosporine treatment is accompanied by down modulation of proinflammatory epidermal cytokines and decreased dermal inflammation. Thus besides suppressing cytokine production by the inflammatory infiltrate, the beneficial effect of cyclosporine in psoriasis also depends on the inhibition of the epidermal cytokine network.BACKGROUND Oral cyclosporine is effective in the treatment of recalcitrant psoriasis. However, the precise mechanism(s) are not fully understood. A possible mode of action may be via down-modulation of proinflammatory cytokines that are increased in psoriatic lesions. OBJECTIVE This study was designed to monitor the effects of cyclosporine treatment on the expression of cytokines, cytokine receptors, and other markers of inflammation in psoriatic skin. METHODS Ten patients with recalcitrant psoriasis were treated with cyclosporine. The in vivo effects of cyclosporine on cytokines and their receptors were studied by the use of cryostat-cut sections and a panel of antibodies. The in vitro effects were studied with flow cytometry of epidermal cell suspensions prepared from psoriatic lesions and control skin. RESULTS Clinical improvement was noted in all patients after 2 weeks of cyclosporine treatment. The expression of interleukin-1 beta, interleukin-8, CD25(IL-2R), CD36 and E-selectin were significantly decreased, whereas the number of tumor necrosis factor-receptor-positive epidermal cells was significantly increased in psoriatic lesions. CONCLUSION Clinical improvement of psoriasis with cyclosporine treatment is accompanied by down modulation of proinflammatory epidermal cytokines and decreased dermal inflammation. Thus besides suppressing cytokine production by the inflammatory infiltrate, the beneficial effect of cyclosporine in psoriasis also depends on the inhibition of the epidermal cytokine network.

Contact allergy to spices

A group of 103 patients suspected of contact allergy was tested with the European standard series, wood tars and spices; paprika, cinnamon, laurel, celery seed, nutmeg, curry, black pepper, cloves, while pepper, coriander, cacao and garlic. 32 patients (Group I) were selected on the basis of positive tests to one or more of possible indicators for allergy to spices: colophony, balsam of Peru, fragrance‐mix and/or wood tars. 71 patients (Group II) showed no response to these indicators. In Group I (n= 32) a statistically significantly higher % of patients (47%) showed positive reactions to 1 or more spices, compared with 15% in Group II (N= 71). Among the spices, the highest numbers of reactions were found to nutmeg (28%), paprika (19%) and cloves (12%) in the indicator‐positive Group I. Fragrance‐mix turned out to be a particularly important indicator allergen, especially for paprika, nutmeg and cloves. The contact allergy in 11 out of 32 (Group I) and 7 out of 25 patch‐tested patients (recruited from Group II) appeared to be‐directed mainly against the ether‐extractable volatile fractions of the spices.