A novel therapeutic approach for granuloma annulare: roflumilast 0.3% cream

Clinical problem Granuloma annulare (GA) is a benign, often self-limiting granulomatous skin disease characterized by erythematous papules or plaques, often arranged in an annular pattern.1 GA predominantly affects women, with a female-to-male prevalence ratio of 3:1, and with peak incidence and prevalence in the fifth decade of life.2 For many women, the associated cosmetic disfigurement causes significant emotional distress. In a survey of 770 patients with GA, 96.7% of whom identified as female, 83.4% reported Skindex-16 emotional subscale scores indicative of a very severe effect on quality of life, and 67.3% cited the appearance of their GA as their primary concern.3 The etiology and pathogenesis of GA remain poorly understood. Some research implicates T helper 1 cell and Janus kinase—signal transducer of activators of transcription dysregulation, with macrophage activation and the release of pro-inflammatory cytokines, including interferon-gamma and tumor necrosis factor-alpha, driving elastic fiber degradation.4 However, conflicting research complicates our understanding of this mechanism. Unfortunately, this limited understanding has resulted in suboptimal treatment options, with responses to standard first-line therapies, primarily topical and intralesional corticosteroids such as triamcinolone, varying widely from 14 to 50%.1 These disappointing and inconsistent outcomes highlight the need for alternative therapeutic options. We present the case of a 19-year-old female with a 3-year history of biopsy-proven GA recalcitrant to topical and intralesional triamcinolone, topical betamethasone, and cryotherapy who presented for further management and treatment. Physical examination revealed a pink annular plaque on the left dorsal index finger and a pink semi-annular plaque with central sparing on the left anterior knee (Fig. 1).Fig. 1.: Granuloma annulare lesion at initial presentation on the left index finger (A) and on the left knee (B).Therapeutic solution The patient was instructed to apply roflumilast 0.3% cream to the affected areas daily for 6 weeks. At the six-week follow-up, complete clearance of the left index finger was observed (Fig. 2). However, the left knee showed residual involvement, prompting intralesional triamcinolone injections during the visit. The patient was instructed to continue roflumilast. At the 12-week follow-up, the knee lesion resolved entirely, leaving only mild postinflammatory hyperpigmentation (Fig. 2).Fig. 2.: Granuloma annulare on the left index finger after 6 weeks of treatment with topical roflumilast (A) and on the left knee following treatment with topical roflumilast and intralesional triamcinolone (B).Phosphodiesterase-4 inhibitors, such as apremilast, have demonstrated some efficacy in GA, prompting the use of topical roflumilast in this case.1 Roflumilast is currently approved by the U.S. Food and Drug Administration for the treatment of plaque psoriasis, seborrheic dermatitis, and atopic dermatitis; however, its potential use for GA treatment has not been studied. By increasing intracellular cyclic adenosine monophosphate levels, roflumilast reduces T helper 1 cell-mediated macrophage activation and the subsequent pro-inflammatory cytokines, which may account for the observed clearance of GA.4 This suggests that roflumilast offers a promising alternative or adjuvant in GA treatment, particularly for patients recalcitrant to conventional therapies. Topical roflumilast is generally well tolerated and minimizes the risk of side effects posed by other therapies, including corticosteroid-induced atrophy and systemic side effects associated with oral phosphodiesterase-4 inhibitors like apremilast.1 Our patient experienced no adverse effects with roflumilast. This case highlights the potential of roflumilast 0.3% cream as both an alternative and adjunctive treatment option for patients with GA, particularly for recalcitrant lesions. The impressive response seen in this case warrants further clinical investigations to validate the efficacy and safety of roflumilast in broader patient populations with GA, potentially offering relief to affected women. Conflicts of interest None. Funding None. Study approval N/A Author contributions HJ participated in the preparation, writing, editing, and review of this manuscript. VS participated in the writing, editing, and review of this manuscript. AY participated in the writing, editing, and review of this manuscript. SM was as the treating physician in this case and contributed to the review of this manuscript. All authors reviewed and approved the final manuscript. Ethics statement Written informed consent was obtained from the patient for the preparation and publication of the manuscript. Informed, written consent was received from all patients for whom photographs are present in the manuscript. Disclaimer This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.