Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis.

An increasingly important approach to the management of patients with severe psoriasis is the concurrent use of two systemic treatments. Previous guidelines have advised against the use of methotrexate and cyclosporin in combination. We report the successful use of a combination of methotrexate and cyclosporin in the treatment of 19 patients with severe, recalcitrant psoriasis, 15 of whom had psoriatic arthropathy. Most patients had previously received two or more systemic treatments. Before combination treatment was started nine of the patients were taking methotrexate and 10 were taking cyclosporin at the maximum tolerated doses. The duration of combination treatment was bimodally distributed, with seven patients having short-term treatment (mean +/- SD duration 18. 9 +/- 15.7 weeks) and 12 patients having long-term treatment (mean +/- SD duration 193.2 +/- 160.6 weeks). Those patients who received short-term treatment did not develop any evidence of toxicity from either agent. Of those patients on long-term treatment, three developed mild impairment of renal function that returned to normal following a reduction in dose of cyclosporin, and three had impairment of renal function (following long-term cyclosporin monotherapy) that improved, but did not normalize, following a reduction in dose of cyclosporin. In each case, combination treatment for psoriasis resulted in good control of both skin and joint problems using lower doses of each agent than would have been used for monotherapy. We conclude that the combination of methotrexate and cyclosporin is an effective treatment for this group of patients.

Nylon cloth macular amyloidosis.

In primary localized cutaneous amyloid, deposition of amyloid is confined to the skin without the involvement of any internal organs. Amyloid deposition in the skin is often scanty, and electron microscopy may be needed to confirm the presence of the typical amyloid fibrils. There have been several case reports of cutaneous amyloidosis associated with friction or rubbing of the skin. We report a case of primary localized cutaneous amyloid associated with the habitual use of a nylon cloth.

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Aberrant cutaneous weal and flare responses in chronic urticaria.

This study examined cutaneous mast cell behaviour in 14 patients with chronic urticaria but no dermographism and 11 healthy controls, by measuring cutaneous weal and flare reactions evoked in response to intradermal challenge injections of 0.1 ml isotonic saline, histamine (20 micrograms), codeine phosphate (10 micrograms) and compound 48/80 (10 micrograms). Five minutes after each injection, the area of the resulting weal and flare was calculated by computer-aided planimetry. The process was repeated at 15, 30 and 45 min following the injection. In patients, saline flares were significantly larger than those of the volunteers at 15, 30 and 45 min (p < 0.05). However, histamine and codeine flare areas were significantly smaller in the patients when compared to the controls at 15, 30 and 45 min (p < 0.05). Compound 48/80 produced smaller reactions in the patients without reaching statistical significance.

Skin surface electron microscopy in Pityrosporum folliculitis. The role of follicular occlusion in disease and the response to oral ketoconazole.

The yeast Pityrosporum orbiculare is thought to cause the folliculitis associated with seborrheic eczema. However, a combination of mechanical and microbiological factors may be involved, with follicular occlusion leading to yeast overgrowth and folliculitis. Scanning electron microscopy was used to investigate this hypothesis. Skin biopsy specimens obtained from patients with Pityrosporum folliculitis were examined by scanning electron microscopy before and after oral ketoconazole therapy. Patients with active disease showed occlusion of noninflamed follicles, which resolved after ketoconazole treatment. Follicular occlusion was not present in biopsy specimens obtained from unaffected controls nor was it related to the presence of P orbiculare. These findings suggest that follicular occlusion may be a primary event in the development of this folliculitis, with yeast overgrowth a secondary occurrence. The beneficial effect of ketoconazole in this disease may be due to direct effects on the follicle.

Skin surface electron microscopy in Pityrosporum folliculitis. The role of follicular occlusion in disease and the response to oral ketoconazole.

The yeast Pityrosporum orbiculare is thought to cause the folliculitis associated with seborrheic eczema. However, a combination of mechanical and microbiological factors may be involved, with follicular occlusion leading to yeast overgrowth and folliculitis. Scanning electron microscopy was used to investigate this hypothesis. Skin biopsy specimens obtained from patients with Pityrosporum folliculitis were examined by scanning electron microscopy before and after oral ketoconazole therapy. Patients with active disease showed occlusion of noninflamed follicles, which resolved after ketoconazole treatment. Follicular occlusion was not present in biopsy specimens obtained from unaffected controls nor was it related to the presence of P orbiculare. These findings suggest that follicular occlusion may be a primary event in the development of this folliculitis, with yeast overgrowth a secondary occurrence. The beneficial effect of ketoconazole in this disease may be due to direct effects on the follicle.

Fragrance sensitivity in coal miners.

In a prospective study, we have examined the incidence of fragrance sensitivity in Nottinghamshire coal miners. Our results confirm previous reports of an increased incidence of such sensitivity in miners (45%) when compared with both male (20%) and female (13%) non-miners. This increased incidence is not related to an increased use of perfumed cosmetics, but may be related to the use of a highly perfumed body lotion in subjects who already have a high incidence of irritant hand eczema. There was no significant increase in the rate of positive reactions to other applied allergens.

Experimental folliculitis with Pityrosporum orbiculare: the influence of host response.

The aetiology of the folliculitis associated with seborrhoeic eczema is unclear, though the yeast, Pityrosporum orbiculare has been implicated. P. orbiculare was applied under occlusion to normal forearm skin of patients with seborrhoeic eczema (SE), seborrhoeic eczema and folliculitis (SEF), and normal controls. There were significant differences in response to occlusion between the three groups. Those patients with previous clinical evidence of folliculitis (SEF) developed folliculitis at the site of occlusion more frequently than either of the other two groups (p less than 0.001), in whom only one patient developed skin changes. This difference was not explained by the response to occlusion alone, nor by natural carriage of yeasts. These results suggest that the yeast P. orbiculare is necessary for the development of folliculitis, but that the nature of the host response determines those patients prone to follicular inflammation.

The dilution of proprietary corticosteroid ointments--an attempt to evaluate relative clinical potencies.

Ten subjects were assessed using the vasoconstrictor assay technique in a double-blind study in order to evaluate the potencies of several diluted and undiluted proprietary corticosteroid ointments. Results showed that clobetasol propionate 0.05% (Dermovate) ointment at a dilution of one part in ten (clobetasol propionate 0.005%) in white soft paraffin was equipotent with betamethasone valerate 0.1% (Betnovate) ointment; and no difference in potency was demonstrated between beclomethasone dipropionate 0.025% (Propaderm), betamethasone valerate 0.1% (Betnovate) and clobetasone butyrate 0.05% (Eumovate).