Subcutaneous Granuloma Annulare: A Rare Case Associated With Acetazolamide

Granuloma annulare (GA) is a benign, granulomatous skin condition characterized by ring-shaped papules or plaques on the dorsal aspects of the hands and/or feet. It is most frequently seen in children and young adults, with a female predominance. Although many cases are idiopathic, associations with certain diseases include autoimmune disorders, diabetes mellitus, and thyroid disease. Drugs have also been implicated including allopurinol, diclofenac, topiramate, amlodipine, thalidomide, and TNF-α inhibitors. The clinical and morphologic distinction from the interstitial granulomatous drug reaction (IDG) can be challenging. Acetazolamide, a carbonic anhydrase inhibitor (CAI) commonly used for idiopathic intracranial hypertension, has recently been associated with subcutaneous granuloma annulare (SGA). We report a 16-year-old girl who developed multiple firm subcutaneous nodules on her hands shortly after initiation and dose escalation of acetazolamide. Histopathology demonstrated subcutaneous palisading granulomas with central necrobiosis, consistent with SGA. Nodules resolved nearly completely within 2 weeks of drug discontinuation. Pharmacologic inhibition of carbonic anhydrase may promote endothelial cell apoptosis leading to ischemic changes in the connective tissue fiber matrix and also modulate macrophage activation resulting in an influx of histiocytes at the site of anoxia, suggesting a potential immunologic mechanism shared with other weak CAIs, such as topiramate. This case highlights acetazolamide-induced SGA and further explores the spectrum of granulomatous inflammation associated with drugs of the CAI class.