Treatment of Recalcitrant Generalized Granuloma Annulare With Adalimumab

December 2011 | Volume 10 | Issue 12 | Case Reports | 1466 | Copyright © December 2011

Tiago Torres MD, Teresa Pinto Almeida MD, Rosario Alves MD, Madalena Sanches MD, Manuela Selores MD

Department of Dermatology, Hospital de Santo AntÓnio, Porto, Portugal


Granuloma annulare is a benign, usually self-limited, dermatosis of unknown cause. Generalized lesions occur in approximately 15 percent of patients with GA and may cause mild to severe cosmetic disfigurement. The treatment of generalized granuloma annulare can be challenging. We report the case of a 36-year-old male patient with a generalized granuloma annulare who had failed topical and systemic glucocorticoids, systemic retinoids, dapsone, minocycline, PUVA therapy, and hydroxicloroquine and was successfully treated with adalimumab, an anti-TNF-α monoclonal antibody. Adalimumab may be an additional option in the treatment of recalcitrant forms of granuloma annulare.

J Drugs Dermatol. 2011;10(12):1466-1468.


Granuloma annulare (GA) is a benign inflammatory skin disease characterized by marginated erythema- tous plaques or nodules that are usually localized to the distal extremities. Although generalized, perforating and subcutaneous variants have also been identified.1 Additionally, although GA tends to be idiopathic, several case reports have shown an association with diabetes mellitus and several malig- nancies. Localized forms of GA are usually asymptomatic and self-limited with spontaneous resolution occurring often with- in 2 years. However, generalized GA (GGA) tends to be more chronic and pruritic, may last for decades, and may cause mild to severe cosmetic disfigurement. The treatment of GGA can be challenging. Systemic steroids can often benefit patients; how- ever high doses are required and usually patients relapse after stopping treatment. Moreover, as GGA is occasionally associ- ated with diabetes mellitus, some patients are contraindicated to steroids therapy. Other systemic treatments include nicotin- amide, PUVA therapy, UVA1, dapsone, pentoxifylline, systemic retinoids, cyclosporine, alkylating agents, and antimalarials.


A 36-year-old male patient presented with disseminated ery- thematous plaques on the trunk, upper, and lower extremities that had persisted for more than five years (Figure 1a). He was otherwise healthy. He had the diagnosis of disseminated granuloma annulare, histopatologically confirmed. He had been treated unsuccessfully with topical and systemic glucocorti- coids, systemic retinoids, dapsone, minocycline, PUVA therapy, and hydroxychloroquine. It was evident that the disease created a high psychological discomfort, mainly for aesthetic reasons.
A new cutaneous biopsy was performed, confirming the di- agnosis (Figure 2), and diabetes mellitus was excluded. Treatment with adalimumab was started, with a subcutaneous injection 80 mg at week 0 and then 40 mg every other week at week 1. Before initiating therapy, the patient was screened for tuberculosis, hepatitis B, and hepatitis C, which were nega- tive. A rapid response to treatment was observed, and at week 4 most of the lesions had showed a remarkable regression. At week 8 all lesions had completely regressed, showing only residual hyperpigmentation (Figure 1b). After 6 months of therapy, without recurrence of the lesions, the treatment was stopped. At the 9-month follow-up after stopping adalimum- ab, the patient continues to be free of lesions.


The use of TNF-α inhibitors (infliximab, adalimumab and etan- ercept) in the treatment of recalcitrant GGA has been reported, showing an effective and rapid response.2-5 TNF-α is critical in the formation of granulomas due to infectious and non-infectious