The incidence of syphilis has historically been cyclical in nature, often in relation to the rise and fall of public health initiatives directed toward eradication along with social attitudes toward sexual practices. The incidence of syphilis has increased by 15% in the last 6 years in the United States, with similar increases worldwide. Herein, we present an atypical case of syphilis presenting with severe septic shock and multiple anogenital lesions in an immunocompetent host. A 22-year-old male with no significant past medical history presented with fevers, chills, sore throat, diaphoresis, and diarrhea. He was febrile, tachycardic, hypotensive, and unresponsive to fluid resuscitation requiring short-term vasopressor support. Physical exam revealed diffuse lymphadenopathy; lower extremity macular rash involving the soles of the feet; papular non-pustular lesions on the scrotum; and a 0.5 cm non-tender irregular, healing lesion on the shaft of the penis. Laboratory analysis was significant for leukocytosis and elevated creatinine. Serum screening rapid plasma reagin was positive, and further testing revealed a titer of 1:32, with confirmation via fluorescent treponemal antibody absorption test. The patient was diagnosed with secondary syphilis, which was determined to be the underlying etiology of the sepsis as all other serological evaluations were negative. He was treated with penicillin G benzathine 2.4 million units intramuscular and supportive management, with improvement of symptoms. The patient engaged in high-risk sexual behaviors, including prior unprotected sexual contact with males. New research indicates that up to one-third of patients may present with atypical cutaneous manifestations, as demonstrated by this patient. It is important for physicians to familiarize themselves with the varied clinical presentations of syphilis, which include multiple anogenital lesions and tender primary lesions in primary or secondary syphilis.

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