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The diagnostic process and discrimination of mucosal lesions present a formidable challenge for numerous clinicians, primarily attributable to the common overlap of clinical manifestations observed across various categories, including infectious, autoimmune, connective tissue, and systemic vascular inflammatory diseases. In cases of mucosal lesions, syphilis presents distinctive characteristics that can help clinicians differentiate it from other conditions. The most common manifestation of primary syphilis is mostly a painless, firm, indurated ulcer known as a chancre, which typically appears at the site of inoculation, with enlargement of regional lymph nodes.

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Although herpes simplex virus, Epstein-Barr virus, and hemophagocytic lymphohistiocytosis are known causes of severe acute liver injury with or without liver failure, these diseases occur almost exclusively in immunocompromised and elderly patients. We report a case of an immunocompetent young man with no medical history who presented with a subacute cough and persistent fevers in the setting of a penile chancre. He was found to have severely elevated liver chemistries and was subsequently diagnosed with hemophagocytic lymphohistiocytosis because of disseminated herpes simplex virus type 1 and Epstein-Barr virus coinfection.

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