fumarates and Sarcoidosis

Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Fumarates; Humans; Middle Aged; Radiography, Thoracic; Rare Diseases; Sarcoidosis; Sarcoidosis, Pulmonary; Severity of Illness Index; Skin Diseases; 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

Fumaric acid esters lead to reduction of cell fusion and inhibition of giant cell formation in vitro, which is considered to be a reason for their therapeutic effect on cutaneous granulomatous diseases. We have reported that successful treatment of the skin lesions of a patient with recalcitrant systemic sarcoidosis with Fumaderm® (Biogen, Munich, Germany; 360-720 mg/day dimethyl fumarate) had to be discontinued due to the development of lymphocytopenia. Therefore, we treated two further patients with the low-dose Fumaderm® Initial (90 mg/day dimethyl fumarate) and observed a partial remission of the skin lesions over a minimum 18 month follow-up without signs of lymphocytopenia.. Fumarsäureester führen zu einer Verringerung der Zellfusion und zur Hemmung der Riesenzellbildung in vitro, die ein Grund für die therapeutische Fumarsäureester-Wirkung auf kutanen Läsionen granulomatöser Erkrankungen sein könnte. Wir berichteten, dass eine erfolgreiche Therapie der Hautveränderungen einer therapieresistenten systemischen Sarkoidose mit Fumaderm® (Biogen, München, Deutschland; 360–720 mg/Tag Dimethylfumarat) aufgrund einer Lymphozytopenie abgebrochen werden musste. Aus diesem Grund behandelten wir 2 weitere Patienten mit dem niedrig dosierten Fumaderm® initial (90 mg/Tag Dimethylfumarat) und beobachteten eine partielle Remission der kutanen Sarkoidose während mindestens 18 Behandlungsmonaten ohne Entwicklung einer Lymphozytopenie.

Topics: Dimethyl Fumarate; Fumarates; Humans; Sarcoidosis; Skin; Skin Diseases

A 43-year-old man with cutaneous and pulmonary sarcoidosis was treated with fumaric acid esters (Fumaderm®) for 11 months because of the cutaneous lesions. During the treatment the cutaneous lesions and pulmonary changes vanished completely. In addition, serum angiotensin converting enzyme (ACE) levels normalized after end of therapy. This case report is one of a few examples of the successful treatment of cutaneous and pulmonary sarcoidosis with fumaric acid esters (Fumaderm®).

Topics: Adult; Dermatitis; Dimethyl Fumarate; Fumarates; Humans; Male; Sarcoidosis; Sarcoidosis, Pulmonary; Treatment Outcome

A 61-year old female patient with cutaneous sarcoidosis was treated with fumaric acid esters (Fumaderm). After 12 months of therapy, lesions were markedly improved and treatment was discontinued. 18 months later, the cutaneous lesions recurred, angiotensin converting enzyme (ACE) serum levels were increased and a chest X-ray demonstrated pulmonary involvement. Therapy with fumaric acid esters was again started. The skin showed improvement after 2 months and completely cleared within 17 months, within 4 months ACE levels normalized, and within 10 months radiologic changes markedly resolved. This case demonstrates a possible role for fumaric acid esters not only in the treatment of cutaneous but also systemic sarcoidosis.

Topics: Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Humans; Immunosuppressive Agents; Middle Aged; Recurrence; Sarcoidosis; Sarcoidosis, Pulmonary; Skin Diseases; Treatment Outcome

Sarcoidosis is a multisystem disease of unknown origin characterized by the formation of noncaseating granulomas, in particular in the lungs, lymph nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used for large disfiguring lesions, generalized involvement, or recalcitrant lesions that did not respond to topical therapy.. We report three patients with recalcitrant cutaneous sarcoidosis who were treated with oral fumaric acid esters (FAE). Three female patients presented with cutaneous sarcoidosis that have proved to be refractory to various therapies, including corticosteroids and chloroquine. We treated the patients with FAE in tablet form using two formulations differing in strength (Fumaderm initial, Fumaderm). Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients. After treatment with FAE (4-12 months), a complete clearance of skin lesions was achieved in the three patients. The side effects observed in this trial correspond to the well-known spectrum of adverse effects of FAE (flush, minor gastrointestinal complaints, lymphopenia).. On the basis of our findings FAE therapy seems to be a safe and effective regimen for patients with recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are necessary to confirm our preliminary results.

Topics: Adult; Dimethyl Fumarate; Female; Fumarates; Humans; Sarcoidosis; Skin Diseases