Generalized granuloma annulare – response to doxycycline

Abstract

EditorGranuloma annulare (GA) is a common non-infectious granulomatous didease. 1,2 Although no clear aetiology has been established, trauma, insect bite reactions, tuberculin skin testing, sun exposure, PUVA therapy, adverse reaction to drugs and viral infections have been proposed as inciting factors. 1 Its pathogenesis is probably immunologic. Evidence suggest that GA represents a cell-mediated immune response to an unknown antigen, in which granuloma formation by macrophage-histiocytes is mediated by interaction with T-helper lymphocytes. It is a Th1-driven inflammatory reaction, with interferon γ-producing lymphocytes eliciting matrix degradation. [3][4][5][6] Nearly 15% of patients with GA have the generalized subtype characterized by a later age of onset, increased prevalence of the HLA-Bw35 allele, protracted course, with only rare spontaneous resolution, and alterations in the lipid profile in about 45% of patients. 1,2,5 A 52-year-old Caucasian woman was observed for asymptomatic erythematous-violaceous annular plaques, with raised borders, symmetrically distributed over the neck and subsequently over the trunk and limbs, evolving for 6 months (Fig. 1). Besides rosacea, the patient was otherwise healthy. Laboratory findings, including autoimmune and hormonal screening, tumoral markers, viral, Borrelia burgdorferi and Treponema pallidum serologies and Mycobacterium polymerase chain reaction were all negative. Skin lesion biopsy showed a granulomatous dermatitis pattern with necrobiotic areas and lymphocytic infiltrate, supporting the diagnosis of GA (Fig. 2).

Granuloma Annulare

“…113 Duarte reported a patient with generalized GA who cleared with 10 weeks of doxycycline (100 mg daily). 114 This patient remained clear at 1 year of follow-up. Treatment with monthly rifampicin, ofloxacin, and minocycline has been reported effective in the treatment of GA. 115,116 Marcus and colleagues 116 treated 6 patients with recalcitrant biopsy-proved GA with 3 months of monthly rifampicin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy.…”

“…Immunosuppression with methotrexate, cyclosporine, and TNF-a inhibitors can be considered in patients with severe disease that has been recalcitrant to other therapies. 28,[87][88][89][90][91][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][114][115][116][117][118][119][120][121][122][123][124]126,127,129,130,[132][133][134][140][141][142][144][145][146][147][148]150,…”

Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and localized granuloma annulare

“…[7] Minocycline reduces collagenase activity, interferes with lymphocyte proliferation, especially T cells, and has an anti-inflammatory effect. [8] Our first patient [ Figure 1], a known case of type 2 diabetes mellitus, hypothyroidism, and osteoarthritis on regular treatment, presented with generalized granuloma annulare, which was confirmed histopathologically. Owing to the lack of response with prolonged oral steroid pulse therapy along with topical superpotent steroids, and the generalized nature of the lesions, she was treated with monthly ROM therapy for 4 months, to which she responded well, with complete clearance of lesions and without experiencing any side effects.…”

“…[6][7][8] Other antimicrobial agents have also been used for the treatment of granuloma annulare, postulating an infectious aetiology. [3] Rifampicin has antimicrobial activity, and can influence antibody formation and cellular immune response, specifically delayed-type hypersensitivity.…”

Generalized granuloma annulare treated with monthly rifampicin, ofloxacin, and minocycline combination therapy

“…In addition, both the conditions respond to dapsone therapy and to prolonged antibiotic use. [8–10] Infections are postulated as one of the possible etiological factors for GA. Shelley reported successful treatment of GA by treating the underlying infections with antibiotics such as cefaclor, cefixime, penicillin, amoxicillin, ciprofloxacin, erythromycin, clarithromycin, and trimethoprim–sulfamethoxazole. [3]…”