fumarates and Granuloma-Annulare

Granuloma annulare (GA) is a benign inflammatory disease associated with many conditions such as malignancy, trauma, thyroid disease, diabetes mellitus, and HIV infection. Common clinical subtypes include localized GA, generalized GA, subcutaneous GA, perforating GA, and patch GA. There exists an abundance of literature on GA, yet we know relatively little about its exact etiology and even less about its treatment. The paucity of conclusive data on effective treatment options is largely because the majority of published studies are limited to small case reports, case series, and retrospective studies. As such, there does not yet exist a gold standard of care to guide clinical management. Depending on the clinical subtype, the clinical prognosis for GA can vary. The localized variant generally self-resolves within 2 years without treatment, whereas the generalized form is more chronic and less responsive to treatment. This focused up-to-date review serves to summarize the latest therapeutic options available for GA.

Topics: Administration, Cutaneous; Administration, Oral; Anti-Infective Agents; Antimalarials; Biological Products; Dermatologic Agents; Diagnosis, Differential; Fumarates; Glucocorticoids; Granuloma Annulare; Humans; Injections, Intralesional; Phototherapy; Remission, Spontaneous; Skin; 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

A 40-year-old man suffered from disseminated granuloma annulare not responding to topical steroids and PUVA-therapy. He was treated with fumaric acid esters and achieved a partial response within 3 weeks, a complete remission after 12 weeks. The literature on fumaric acid esters in granuloma annulare is reviewed.

Topics: Adult; Drug Administration Schedule; Fumarates; Granuloma Annulare; Humans; Male; Skin; Tablets; Treatment Outcome

The therapy of disseminated granuloma annulare has often limited success. Treatment of granuloma annulare with fumaric acid esters (FAE) has recently been reported to be effective in 2 patients.. To assess the efficacy of a systemic therapy with FAE in consecutive patients with disseminated granuloma annulare.. Eight patients with disseminated granuloma annulare were treated with FAE in tablet form according to the standard therapy regimen used in psoriasis. The colour and the elevation of the skin lesions were assessed by a visual analogue scale before and after therapy.. Systemic therapy with FAE induced a significant clinical improvement in elevation and colour of skin lesions, with remission in 3 and partial remission in 4 patients. One patient remained unchanged. Side-effects associated with the therapy were seen in 6 patients.. Systemic therapy with FAE can be effective in patients suffering from disseminated forms of granuloma annulare, but side-effects of FAE have to be taken into consideration.

Topics: Administration, Oral; Adult; Aged; Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Granuloma Annulare; Humans; Middle Aged; Severity of Illness Index; Treatment Outcome

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

Topics: Aged; Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Granuloma Annulare; Humans

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Child; Esters; Female; Fumarates; Granuloma Annulare; Humans; Male; Middle Aged; Photochemotherapy; Retrospective Studies; Young Adult

While localized variants of granuloma annulare are typically self-limited, disseminated granuloma annulare tends to be chronic and often therapy-resistant. Treatment with fumaric acid esters is effective for severe forms of psoriasis. Disseminated granuloma annulare has also been reported to respond to fumaric acid esters. We treated 8 patients (mean age 64.2 years; 4 men, 4 women) with low-dose fumaric acid esters for 1-18 months. One patient showed complete clearance, 4 marked improvement, one slight to moderate improvement and one no response. One patient discontinued treatment due to nausea after one month and another stopped it after 18 months. Five out of 8 patients tolerated the treatment well. Six patients developed transient, mild leucopaenia and one eosinophilia. None of these blood abnormalities necessitated discontinuation of therapy. Low-dose fumaric acid esters significantly improve disseminated granuloma annulare in approximately 63% of patients. Larger, controlled, prospective studies are needed to evaluate its efficacy and safety in this setting.

Topics: Administration, Oral; Dermatologic Agents; Dimethyl Fumarate; Female; Fumarates; Granuloma Annulare; Humans; Male; Middle Aged; Treatment Outcome

Topics: Aged; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Elbow; Esters; Female; Follow-Up Studies; Forearm; Fumarates; Granuloma Annulare; Granuloma, Giant Cell; Humans; Immunohistochemistry; Male; Severity of Illness Index; Skin Diseases; Treatment Outcome

Granuloma annulare is a granulomatous disease of unknown etiology. Various therapies have been tried in disseminated granuloma annulare (DGA), including corticosteroids, several variants of psoralen plus ultraviolet-A radiation, ultraviolet- A1 radiation, systemic retinoids, and dapsone, with variable success. We report a patient with recalcitrant DGA who was treated with fumaric acid esters (FAE).. A 40-year old Caucasian woman presented with a 25-year history of recalcitrant DGA. On both legs and the abdomen there were erythematous annular plaques. She was treated with FAE in tablet form using two formulations differing in strength (low strength tablets: 30 mg dimethylfumarate, 67 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt; high strength tablets: 120 mg dimethylfumarate, 87 mg monoethylfumarate Ca salt, 5 mg monoethylfumarate Mg salt, 3 mg monoethylfumarate Zn salt). After three-month therapy, an almost complete clearance of skin lesions was achieved. With the exception of temporary lymphopenia, no adverse effects were observed. The patient remained in remission during a six-month follow up period.. Our observation has demonstrated that FAE is a potentially beneficial therapeutic option for patients with recalcitrant DGA. However controlled trials are necessary to fully explore the efficacy, optimal dosage, and safety of FAE in the management of DGA.

Topics: Adult; Dermatologic Agents; Female; Fumarates; Granuloma Annulare; Humans

A 64-year old female patient was treated for a therapy-resistant generalized granuloma annulare with fumaric acid esters (Fumaderm initial). One week following begin of therapy with an initial dose of 30 mg per day, the papules had regressed significantly. A 6-week therapy with a final dose of 90 mg Fumaderm initial per day led to a nearly complete healing of the illness.

Topics: Dermatologic Agents; Dimethyl Fumarate; Female; Follow-Up Studies; Fumarates; Granuloma Annulare; Humans; Immunosuppressive Agents; Middle Aged; Skin; Time Factors