The global outbreak of Mpox has resurged, leading to a significant increase in cases across numerous countries. Mpox infections are associated with potential ophthalmologic complications, such as periorbital skin lesions, blepharoconjunctivitis, keratitis, and vision impairment. Here, we present a retrospective case report of an atypical Mpox in an HIV-positive patient with a persistent 5 × 5 cm ulcerated, round, plaque-like eyelid lesion refractory to multiple treatment regimens. Upon serologic Mpox identification, the patient was promptly started on antiviral therapy with the resolution of symptoms. This case demonstrates the importance of considering Mpox in the differential diagnosis of atypical periorbital lesions in HIV-positive patients. We also wish to highlight the potential bias toward focusing on opportunistic infections in those with HIV, which can delay diagnosis.
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