What are the treatment options for generalized granuloma annulare?

Updated: Oct 15, 2020
  • Author: Ruby Ghadially, MBChB, FRCP(C)Derm; Chief Editor: William D James, MD  more...
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Generalized granuloma annulare tends to be more persistent and unsightly. Treatment of the generalized disease is unfortunately fraught with a lack of consistently effective options. Over the last 10-15 years, success with the use of ultraviolet (UV) B, mostly narrowband UVB, a relatively harmless treatment compared with the alternatives, has made this a first-line option for generalized granuloma annulare. Multiple groups have described single or small groups of cases, [29, 30, 31, 32, 33, 34] and, in 2015, a retrospective analysis of 13 cases of generalized granuloma annulare treated with narrowband UVB was published. [35]

The available literature supports the use of phototherapy with oral psoralen and UVA (PUVA) as first-line options for generalized granuloma annulare. [36, 37, 38, 39] However, the risks of malignancy when treating an essentially benign condition must be discussed.

Isotretinoin may be a first-line option based on many case reports. [40, 38, 39, 41, 42, 43, 44, 45, 46]

Antimalarials may also be quite effective, as revealed in a large case series [47] and individual reports. [48, 49] Grewal et al found chloroquine to give the highest response, although hydroxychloroquine was also useful. [47]

Piaserico et al report successful therapy for long-standing generalized granuloma annulare using methyl aminolevulinate photodynamic therapy. [50] Weisenseel et al reported moderate success with photodynamic therapy using 20% 5-aminolevulinic acid (ALA) gel. [51] Cazavara-Pinton et al reported responses in 9 of 13 patients. [52]

Marcus et al report on 6 patients with granuloma annulare that was refractory to standard treatment. The patients were treated with monthly combination therapy including rifampin at 600 mg, ofloxacin at 400 mg, and minocycline hydrochloride at 100 mg monthly for 3 months. Three to 5 months after the initiation of treatment, the plaques were cleared completely. Postinflammatory hyperpigmentation was reported by some patients. Although the treatment was successful, the authors suggested further studies may be needed to confirm this combination therapy as a successful option for recalcitrant granuloma annulare. [53] Garg and Baveja also reported successful treatment of 5 cases of generalized granuloma annulare with the same three antibiotics. [54]

Other anecdotal reports and small series describe successful systemic treatment with dapsone, [55, 56, 57, 58] steroids, pentoxifylline, [59, 60] cyclosporine, fumaric esters, [61] interferon-gamma, potassium iodide, nicotinamide, etanercept, [62, 63, 64, 65] infliximab, [66, 67, 68] adalimumab, [69, 70, 71, 72, 73, 74] Janus kinase (JAK) inhibitors, [75, 76, 77] and apremilast. [78, 79]

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