fumarates and Necrobiosis-Lipoidica

Necrobiosis lipoidica (NL) is a rare granulomatous disease of hitherto unclear etiology frequently seen in patients with diabetes. Characterized by its potential for ulcerations, it often presents a serious burden for those affected. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intralesional corticosteroids does not always show satisfactory results. We therefore set out to evaluate whether the various treatment regimens published since 2000 have actually expanded the therapeutic armamentarium in a relevant manner. Included were all publications that described more than one patient being treated with any given therapeutic modality. Overall, we analyzed data for 16 different treatment regimens reported in 49 publications. The largest amount of data exists for topical PUVA therapy, photodynamic therapy (PDT), and systemic treatment with fumaric acid esters. Remarkably, our analysis showed that with an increase in the number of documented patients treated with a given therapeutic modality, the proportion of those achieving a complete or partial response actually decreased. This was interpreted as publication bias. Thus, no clear recommendation can be given for second-line therapy in case topical or intralesional corticosteroids fail.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Combined Modality Therapy; Evidence-Based Medicine; Fumarates; Humans; Necrobiosis Lipoidica; Photochemotherapy; PUVA Therapy; Treatment Outcome

Fumaric acid esters have been used successfully in the therapy of psoriasis vulgaris since 1959. In the last 17 years, many of the underlying mechanisms of anti-psoriatic action, such as a Th1/Th2 shift, a suppression of important leukocyte adhesion molecules, the induction of pro-apoptotic pathways in T-cells and recently anti-angiogenic action, have been discovered. Based on the knowledge of these immunomodulatory characteristics, fumaric acid esters have been shown to be effective or potentially effective in a multitude of dermatological as well as non-dermatological diseases. The range of new therapeutic targets reaches from multiple sclerosis to illnesses such as necrobiosis lipoidica, granuloma annulare and sarcoidosis. Experimental approaches offer promising, although preliminary, results on the treatment of cancer, malaria, chronic inflammatory lung diseases, and Huntington disease, to name but a few. This valued and well-known drug mainly prescribed by dermatologists is now experiencing a renaissance far beyond dermatologic applications.

Topics: Dermatologic Agents; Dimethyl Fumarate; Fumarates; Granuloma Annulare; HIV Infections; Humans; Immunosuppressive Agents; Multiple Sclerosis; Necrobiosis Lipoidica; Neoplasms; Off-Label Use; Sarcoidosis

Noninfectious granulomatous skin diseases are inflammatory disorders of unknown aetiology which are often recalcitrant to common anti-inflammatory treatment regimens. Recently, in several case reports, fumaric acid esters (FAE) have proved beneficial in granulomatous skin diseases, but studies on a larger collection of consecutive patients have not yet been performed.. To investigate the therapeutic efficacy of FAE for the treatment of granulomatous skin diseases.. The therapeutic efficacy and side-effects of FAE were analysed retrospectively in 32 patients with disseminated granuloma annulare (n = 13), annular elastolytic giant cell granuloma (n = 3), sarcoidosis (n = 11), necrobiosis lipoidica (n = 4), or granulomatous cheilitis (n = 1).. Three patients discontinued treatment within 4 weeks because of side-effects. Of the remaining 29 patients, 18 patients responded to treatment with FAE. Marked improvement or complete clearance was seen in seven patients. We observed a slight to moderate improvement in 11 patients, and 11 patients did not respond. In patients showing a complete remission, the maximum effect was observed after 8.5 months (SD +/-6 months, range 3-20 months). In two patients with systemic sarcoidosis, the pulmonary changes improved in parallel with the skin. Side-effects were usually mild and resolved spontaneously upon dose reduction or discontinuation of the therapy.. The data presented here indicate that FAE may be considered for the treatment of recalcitrant granulomatous skin disease.

Topics: Adolescent; Adult; Aged; Cheilitis; Drug Administration Schedule; Esters; Female; Fumarates; Granuloma Annulare; Granuloma, Giant Cell; Humans; Male; Middle Aged; Necrobiosis Lipoidica; Retrospective Studies; Sarcoidosis; Skin Diseases

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.. We sought to investigate the efficacy of FAE in a larger number of patients with NL.. 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.. 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.. The results of this study demonstrate that FAE are beneficial and safe in the treatment of patients with NL.

Topics: Adult; Aged; Aged, 80 and over; Dermatologic Agents; Dimethyl Fumarate; Drug Combinations; Female; Fumarates; Humans; Leg Dermatoses; Male; Middle Aged; Necrobiosis Lipoidica; Prospective Studies; Severity of Illness Index; Skin; Treatment Outcome; Ultrasonography

Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease.. We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy.. Comorbidity and the efficacy of the applied treatment was assessed for 98 patients.. We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy.. Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.

Topics: Adolescent; Adult; Calcineurin Inhibitors; Cluster Analysis; Comorbidity; Dapsone; Diabetes Mellitus; Female; Fumarates; Humans; Male; Necrobiosis Lipoidica; Retrospective Studies; Steroids; Thyroid Diseases; Young Adult

Topics: Adult; Biopsy; Dermatologic Agents; Female; Fumarates; Glucocorticoids; Humans; Necrobiosis Lipoidica; Phototherapy; Severity of Illness Index; Skin; Skin Ulcer; Treatment Outcome

Topics: Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Humans; Middle Aged; Necrobiosis Lipoidica