A 24-year-old man comes to the emergency department due to a few hours of fever with rigors, headache, and myalgias. While at an urgent care center last night, he was diagnosed with syphilis and received a dose of intramuscular benzathine penicillin G. The patient has a history of HIV infection, and a recent CD4 count was 540/mm³. He is not currently taking antiretroviral therapy and takes no other medications. He continues to have unprotected intercourse with several partners despite counseling. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 38 C (100.4 F), blood pressure is 90/60 mm Hg, and pulse is 110/min. The patient is diaphoretic and appears uncomfortable. A diffuse, faint, macular rash involving the palms and soles is present. Genital examination shows a nontender ulcer with induration and several enlarged inguinal lymph nodes. Which of the following is the most likely cause of this patient's current condition?

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11ec25c8_d46e_f181_bc81_713bcd1aa2d9_MD0003_00 This patient with primary syphilis (chancre) received a dose of penicillin G last night and now has the Jarisch-Herxheimer reaction. Approximately 10%-35% of patients with early syphilis develop this reaction following antibiotic therapy initiation. It is caused by the rapid destruction of spirochetes, which results in a release of large quantities of lipoproteins into the systemic circulation. Patients typically develop an acute febrile illness <12 hours after antibiotic initiation; symptoms can include fever, myalgias, rigors, sweating, hypotension, and worsened syphilitic rash (diffuse, macular, including palms and soles). Manifestations are usually self-limited and resolve spontaneously within 48 hours. The Jarisch-Herxheimer reaction may also occur after the treatment of other spirochetes (eg, Borrelia burgdorferi) or atypical organisms (eg, Bartonella). (Choice A) Anaphylactic reactions typically occur within minutes (not several hours) after drug exposure. Although hypotension is frequently present, urticarial (not macular) rash and respiratory symptoms are usually prominent. (Choice B) Coinfection with multiple sexually transmitted infections is common. However, gonococcus typically causes urethritis rather than posttreatment, acute-onset hypotension and systemic symptoms; it is not commonly associated with a macular rash. (Choice C) Syphilis is universally susceptible to penicillin; therefore, treatment failures are primarily seen when alternate regimens (eg, doxycycline) are used instead of penicillin. (Choice D) Immune reconstitution inflammatory syndrome occurs in patients with HIV within days or weeks of antiretroviral initiation. It is marked by a paradoxical worsening of concurrent infectious symptoms due to immune system improvement. This patient was not started on antiretroviral treatment. Educational objective: The Jarisch-Herxheimer reaction is an acute, febrile reaction that commonly occurs <12 hours after initial treatment of syphilis. Symptoms include fever, headache, myalgias, rigors, sweating, hypotension, and worsening syphilitic rash (if present). Manifestations are self-limited and typically resolve spontaneously within 48 hours.

A 24-Year-Old Man Comes to the Emergency Department Due to a Few