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