In the past couple of years, new literature has been published on the topic of GA and we have gained a better understanding of GA epidemiology; recent studies have also helped further elucidate its pathogenesis by identifying Th1, JAK-STAT, and perhaps also Th2 pathway dysregulation in GA lesional skin. The long-debated association between GA and DM now seems to be established, while the link between GA and malignancy remains controversial. New bacterial and viral triggers have also been reported, although it remains unlikely that they unilaterally induce GA. A number of reports of iatrogenic GA have also been recently added to the literature, although the pathogenesis of these drug eruptions eludes facile explanation, as there is some overlap between the drugs that induce GA and the drugs that treat it.
In regard to therapy, several case reports, case series, and observational studies have emerged that present compelling response to certain treatments, although the significance of their findings remains limited. Large retrospective studies seem to support the efficacy of topical and intralesional corticosteroids in some but not all patients. For GA refractory to corticosteroids, other therapies may need to be utilized. Phototherapy remains the most well-studied option, but recent reports emphasize that not all patients undergoing phototherapy respond. Furthermore, financial and logistical considerations remain barriers to accessing this treatment modality. Dapsone, HCQ, methotrexate, pentoxifylline, and sulphasalazine are cheaper, orally available therapies that have been reported to be of some efficacy in larger retrospective studies and may also be considered viable second-line therapies for GA. Targeted immunomodulators, such as apremilast and tofacitinib, and biologic therapies (such as TNFα inhibitors and dupilumab) may also be indicated off-label in GA, although the evidence base for these therapies is limited to isolated case reports and small case series. Management of common comorbidities (e.g. diabetes and hyperlipidemia) may also be adjunctive.
Considering the findings of our review, we propose a therapeutic ladder for the management of GA, with the first rung being topical and intralesional corticosteroids. If patients do not respond to corticosteroids, therapy can be escalated to the second rung, i.e. dapsone, HCQ, methotrexate, pentoxifylline, and sulphasalazine. If GA still remains recalcitrant to treatment, then phototherapy and targeted immunomodulators, such as apremilast and tofacitinib, or biologic therapies (adalimumab, dupilumab, etanercept, and infliximab) may be considered. Finally, it is worth emphasizing that GA (commonly the localized variant but only rarely the disseminated variant) is a self-limited disease and can resolve of its own accord. Thus, in patients who do not desire treatment of lesions for cosmetic reasons, simple reassurance regarding the benign nature of GA may suffice.
Now more than a century has passed since Dr. Colcott-Fox described a 'ringed eruption of the fingers', yet the precise etiopathogenesis and treatment of GA remains defiantly elusive. Current literature on GA treatment is limited to observational studies; there remains a paucity of randomized controlled trials, and a gold standard for GA treatment is yet to be identified. Further studies on some of the therapies we have reviewed may be warranted so that evidence-based therapies for GA can be established.
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Am J Clin Dermatol. 2022;23(1):37-50. © 2022 Adis Springer International Publishing AG