Case Presentation: A 51-year-old man with type 2 diabetes presented with icterus and generalized, non-pruritic, well-circumscribed, red, papular eruptions, including on his palms and soles. He had no fever, malaise, or arthralgia and no recent/current medication use; he drank alcohol only socially. He had conjunctival icterus and several tiny mucous patches in the oral mucosa. Ultrasound and computed tomography revealed no evidence of obstructive biliary disease or liver tumors. Laboratory examination revealed liver dysfunction, with markedly elevated ALP levels (4446 IU/L). Conjugated hyperbilirubinemia was subsequently diagnosed. Serology was negative for hepatitis B and C virus. Secondary syphilis was suspected because of the characteristic distribution of red, papular eruptions and history of unprotected sexual contact with a female sex worker 2 months ago. A positive rapid plasma reagin (RPR) test (1:16), presence of Treponema pallidumagglutination (27.02 signal-to cutoff ratio), and absence of antibodies to HIV were confirmed. Liver biopsy on hospitalization revealed lobular inflammation with focal necrosis of hepatic cells, with no cholestasis, liver fibrosis, or spirochetes. Because the pathological findings were consistent with syphilitic hepatitis, the patient was diagnosed with syphilis infection and subsequent hepatitis, i.e., syphilitic hepatitis in the absence of an alternative cause of hepatitis. He developed a high fever, which was assumed to be a Jarisch–Herxheimer reaction to the penicillin G therapy; there were no other symptoms/adverse effects. Liver dysfunction improved concomitantly with syphilis therapy; the eruptions resolved 3 months after penicillin G treatment. A normal RPR test was confirmed 5 months after discharge.

Discussion: The number of patients with primary and secondary syphilis has been increasing globally since 2000. Secondary syphilis is one of three stages of syphilis caused by T. pallidum. It generally occurs 4–10 weeks after unsafe sexual contact and presents with diverse symptoms, such as mucocutaneous lesions, lymphadenopathy, and systemic flu-like symptoms. Syphilitic hepatitis is rare in early syphilis infections. Elevated ALP levels are prominent but hyperbilirubinemia is relatively rare in syphilitic hepatitis. Liver biopsy may be nonspecific and is typically characterized by periportal lymphocytic infiltration with focal necrosis of hepatic cells around veins, portal areas, and lobules. The possible mechanism of acute liver failure in syphilitic hepatitis is thought to be either a direct reaction to Treponemaor an autoimmune response. Syphilitic hepatitis generally has a favorable prognosis if adequate treatment is initiated.

Conclusions: Physicians should consider secondary syphilis when a patient has a characteristic pattern of exanthema including the palms and soles and a history of unsafe sexual contact. Furthermore, syphilis may present with a variety of clinical manifestations, such as liver dysfunction, as observed in our patient. Syphilis is not a disease of the past.