ABSTRACT
BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous skin disease with association to diabetes mellitus. To date, no proven effective therapy for NL has been implemented. The standard treatment is topical application of corticosteroids, but numerous agents have been reported for NL, with varying degrees of success. In recent case reports, fumaric acid esters (FAE) have been reported to be effective in granulomatous skin diseases such as granuloma annulare, cutaneous sarcoidosis and NL. OBJECTIVES: We sought to investigate the efficacy of FAE in a larger number of patients with NL. METHODS: Eighteen patients with histopathologically proven NL were consecutively recruited into a prospective noncontrolled study. Dosage of FAE was given according to the standard therapy regimen for psoriasis. FAE were administered for at least 6 months. The treatment outcome was evaluated by means of clinical and histological scoring and 20-MHz ultrasound assessments. RESULTS: Three patients discontinued therapy with FAE, while the remaining 15 patients finished the study. After a mean +/- SD treatment period of 7.7 +/- 2.9 months, a significant (P < 0.001) decrease in the mean +/- SD clinical score, from 7.4 +/- 1.8 at the beginning to 2.5 +/- 1.3 at the end of therapy, was observed. Significant clinical improvement of NL was accompanied by significant (P = 0.019) increase of dermal density as assessed by means of 20-MHz ultrasound, and significant (P = 0.011) reduction of the histological score. Adverse effects were moderate and consisted mainly of gastrointestinal complaints and flushing. During follow-up of at least 6 months, clinical outcome remained stable in all patients. CONCLUSIONS: The results of this study demonstrate that FAE are beneficial and safe in the treatment of patients with NL.
Subject(s)
Dermatologic Agents/therapeutic use , Fumarates/therapeutic use , Leg Dermatoses/drug therapy , Necrobiosis Lipoidica/drug therapy , Adult , Aged , Aged, 80 and over , Dermatologic Agents/adverse effects , Dimethyl Fumarate , Drug Combinations , Female , Fumarates/adverse effects , Humans , Leg Dermatoses/diagnostic imaging , Leg Dermatoses/pathology , Male , Middle Aged , Necrobiosis Lipoidica/diagnostic imaging , Necrobiosis Lipoidica/pathology , Prospective Studies , Severity of Illness Index , Skin/diagnostic imaging , Treatment Outcome , UltrasonographyABSTRACT
BACKGROUND: Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE: The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS: A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS: The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION: Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.
Subject(s)
Fumarates/therapeutic use , Psoriasis/drug therapy , Abdominal Pain/chemically induced , Adult , Aged , Diarrhea/chemically induced , Dimethyl Fumarate , Double-Blind Method , Drug Combinations , Female , Flushing/chemically induced , Fumarates/administration & dosage , Fumarates/adverse effects , Humans , Joints/drug effects , Male , Middle Aged , Pain/physiopathology , Placebos , Psoriasis/physiopathology , Remission InductionABSTRACT
A histological-immunohistological study was conducted to investigate the effect of systemically administered fumaric acid esters (FAEs) on epidermal thickness and composition of the inflammatory infiltrate in psoriatic plaques. The very first effect of systemic therapy with FAEs is the disappearance of CD 15-positive cells in the beneath the epidermis, accompanied by a significant reduction in T-helper cells beneath the epidermis, pointing to an immunosuppressive effect. This is followed after some delay by a reduction in acanthosis and hyperkeratosis. The reduction in infiltrating T-lymphocytes corresponds to that seen after systemic or intralesional therapy with cyclosporin. However, the normalization of the psoriatic plaques takes longer under the influence of FAEs than under cyclosporin.
