Abstract: Adult-onset xanthogranuloma (AOX) is one of the four rare syndromes collectively referred to as adult xanthogranulomatous disease (AXD). It primarily occurs in the orbit and ocular adnexa and displays distinctive histopathological features, characterized by the infiltration of non-Langerhans-derived foam-like histiocytes and Touton giant cells. The presence of diffuse yellow plaques on the eyelids serves as a highly indicative feature. In this report, we present a compelling case of bilateral periorbital AOX. Initially, the patient received a diagnosis of necrotizing xanthogranuloma (NBX) and underwent treatment with dapsone, which yielded a poor response. Subsequently, through repeated biopsy, immunoprotein electrophoresis, and high-throughput sequencing, the diagnosis was revised to AOX. Subsequently, the patient’s treatment was modified to include oral hormone therapy, and no further progression of the periorbital plaque was observed. Notably, the patient’s sister was diagnosed with xanthelasma palpebrarum (XP), suggesting a potential genetic association between AOX and XP. Unfortunately, the sister declined further histologic examination and genetic sequencing of her skin lesions, impeding the acquisition of additional evidence regarding the genetic link between these two disorders. Despite the divergent pathological features, pathogenesis, and clinical presentation of AOX and xanthelasma palbrarum, clinicians should remain cognizant of the plausible genetic correlation between these two conditions and pursue further investigations when feasible.

Keywords: adult-onset xanthogranuloma, adult xanthogranulomatous disease, histopathology, protein electrophoresis