Low Dose Pegylated Interferon Alpha as a First‐Line Treatment for Necrobiotic Xanthogranuloma

Necrobiotic xanthogranuloma (NXG) is a rare, progressive granulomatous disorder frequently associated with monoclonal gammopathy, particularly monoclonal gammopathy of undetermined significance (MGUS). It typically presents with indurated to ulcerative yellowish plaques or nodules, often with ocular involvement. Due to its rarity, no standardized treatment exists, and responses to reported therapies are variable. We present the case of a 53‐year‐old woman initially diagnosed with granuloma annulare who later developed biopsy‐confirmed NXG with associated IgG lambda MGUS. Given progressive cutaneous and ocular disease and prior institutional success with pegylated interferon alpha‐2a (PEG‐IFN‐α‐2a), this therapy was initiated as first‐line treatment. The patient responded favourably to a low dose (67.5 mcg weekly), with significant regression of lesions and gradual reduction in paraproteinemia. A trial of dose escalation was limited by side effects, but clinical improvement continued at the lower dose, allowing for spacing of doses to fortnightly. PEG‐IFN‐α‐2a is known to exert antiproliferative, antiviral and immunomodulatory effects, though its mechanism in NXG remains unclear. This case supports PEG‐IFN‐α‐2a as a potentially effective and well‐tolerated first‐line therapy for progressive NXG, particularly in the setting of MGUS. Further studies are needed to elucidate the pathophysiology of NXG and to guide targeted therapeutic strategies.