Successful treatment of disseminated granuloma annulare with oral fumaric acid esters

annulare with oral fumaric acid esters Granuloma annulare (GA) is a granulomatous disease of unknown etiology with typical histological features. It is a benign skin problem characterized by a chronic course and without any subjective symptoms; associated with diabetes mellitus in up to 20% of cases. In some cases, the disease may develop after the treatment with certain drugs, ultraviolet radiation, infections, insect bite, or local trauma. Although spontaneous resolution can occur in some cases, various therapies have been tried in disseminated GA (DGA), including corticosteroids, cyclosporine, methotrexate, isoniazid, several variants of phototherapy, systemic retinoids, dapsone, and potassium iodide with variable success. Successful treatment of psoriasis with fumaric acid esters (FAE) has been well documented since the 1990s. In recent reports, FAE have been reported as effective in noninfectious granulomatous skin diseases, such as GA, cutaneous sarcoidosis, necrobiosis lipoidica, and annular elastolytic giant cell granuloma. Other treatment options for GA have also been tried (e.g. tumor necrosis factor alpha antibody, methotrexate, and topical imiquimod). We studied two cases of DGA treated with systemic FAE (two female Caucasian patients – both aged 66 years). One of them has had the disease for 14 years and the other for five years (Fig. 1). The disease was localized on both the upper and lower extremities and abdomen, affecting over 30% of the body surface area. Histological examination of a biopsy specimen revealed the characteristic findings for the diagnosis of DGA. Complete work-up did not reveal any evidence of malignancies, infections, and other internal diseases such as diabetes mellitus. Various treatments were tried, including potassium iodide, ultraviolet, and topical steroids, without any good results. After signing a written consent form, patients started oral treatment with FAE (Fumaderm – containing dimethylfumarate [120 mg] with lower concentrations of the calcium, magnesium, and zinc salts of monoethylfumarate). The regimen with FAE was, first, one Fumaderm tablet daily (120 mg) until a maximum dose of two Fumaderm tablets three times per day was achieved (total dose of 720 mg daily) in the sixth week. If side effects occurred, the patient’s dosage was reduced to the previously tolerated dose. Regular laboratory investigations, including serum creatinine, blood urea, serum transaminases, bilirubin, urine chemistry, and complete hematological values with differential blood count were done. The first patient was treated for 36 months with a 2-month interval in the treatment. Complete remission was achieved on the abdomen and upper extremities after three months, while it took six months of treatment for complete clearance on the legs (Fig. 2). This may be due to the longstanding lesions on the legs. Recurrence of the disease occurred after two months of discontinuation. She started re-treatment in low dose (two capsules/day) for more than two years with almost complete remission. She is taking low-dose fumarate all the time as a maintenance therapy. The second patient was treated for more than nine months. A significant reduction of elevation and redness was observed within two months. After one year, the patient decided to discontinue the treatment because she found the results of the treatment satisfactory. Adverse events, usually mild and transitory, consist of itching, flushing, diarrhea, and stomach pains. Furthermore, no other subjective side effects were observed with