Off-label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study.

BACKGROUND: Fumarates are approved for the systemic treatment of moderate and severe psoriasis vulgaris in Germany. However, a number of studies and case reports indicate their efficacy in the treatment of further inflammatory skin disorders or granulomatous skin diseases. OBJECTIVES: To examine the efficacy and safety of fumarates for the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. PATIENTS AND METHODS: The therapeutic efficacy and side-effects of fumarate therapy were analysed retrospectively in patients with granuloma annulare (GA, n = 4), cutaneous sarcoidosis (SA, n = 1), lichen planus (LP, n = 3), pityriasis rubra pilaris (PRP, n = 1) or chronic discoid lupus erythematosus (CDLE, n = 1). RESULTS: Six patients (GA: 3/4; LP: 2/3; PRP: 1/1) showed complete clearance and two patients (GA: 1/3; SA: 1/1) had a partial response, and the CDLE patient showed stable disease under a combination therapy with hydroxychloroquine. Side-effects associated with fumarate therapy were seen in seven of ten patients and resolved spontaneously upon dose reduction or discontinuation of the therapy. CONCLUSION: According to this data, fumarates may represent a new approach in the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. For the first time, the successful treatment of LP and CDLE with fumarates is reported. Side-effects are not limiting in most cases, but can hamper a dose escalation.

Treatment of active psoriatic arthritis with the PPARgamma ligand pioglitazone: an open-label pilot study.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory joint disease, in which early neovascularization of affected skin and synovial tissue represents an important pathogenetic step in the disease process. Activation of the peroxisome proliferator activated receptor gamma (PPARgamma) showed anti-inflammatory effects in several in vitro and in vivo models (e.g. collagen-induced arthritis) by inhibition of angiogenesis and suppression of proinflammatory cytokines. Therefore, we studied the use of pioglitazone, a PPARgamma agonist originally developed for the treatment of diabetes, in patients with PsA. METHODS: Ten patients with active PsA, seven males and three females, who showed at least two tender and two swollen joints despite stable treatment with an NSAID, were enrolled in this open-label study. All patients received a daily dose of 60 mg pioglitazone while continuing their current NSAID therapy. The primary endpoint was the PsARC (Psoriatic Arthritis Response Criterion); the secondary endpoints included the ACR20 response and improvement in the Psoriasis Area and Severity Index (PASI) in patients with more than 2% skin involvement. Patients were evaluated for endpoints at baseline and after 12 weeks. RESULTS: After 12 weeks, six of 10 patients met the PsARC. The ACR20 response was achieved in five patients. The mean percentage reduction in PASI was 38%, with a clinically meaningful PASI 50 response in two of six patients. Median tender joint count (interquartile range) decreased from 12.0 (8.0-18.0) to 4.0 (2.0-10.0), and the median swollen joint count from 5.0 (4.0-8.0) to 2.0 (1.0-7.0) (P<0.05 for both). Median Health Assessment Questionnaire score changed from 1.0 (0.375-1.375) to 0.75 (0.375-1.0) (P<0.05). Three patients had to be withdrawn from the study due to inefficacy and side-effects. Major side-effects were oedema of the lower extremities and increase in weight. CONCLUSIONS: Treatment with a PPARgamma agonist appears to be a promising therapeutic principle in PsA, but the use of PPARgamma ligands might be limited by side-effects such as increase in weight and fluid retention.