Six hours after receiving benzathine penicillin G for secondary syphilis, a 25-year-old man develops fever with rigors, myalgia, headache, and worsening of his rash. Blood pressure is stable. What is the underlying mechanism?

• A IgE mediated type I hypersensitivity to penicillin
• B Direct pyrogenic effect of penicillin on hypothalamic thermoregulatory centers
• C Immune complex deposition in small vessels
• D Release of lipopolysaccharide from lysed spirochetes ✓

Explanation

This is the Jarisch-Herxheimer reaction, an acute febrile reaction occurring within hours of starting therapy, classically in secondary syphilis. Massive killing of treponemes releases endotoxin-like lipoproteins (Tpr proteins and membrane lipoproteins) that trigger TNF-alpha, IL-6, and IL-8 release, causing fever, chills, hypotension, and exacerbation of lesions. It is self-limiting and managed supportively with antipyretics; it is not an allergic reaction, so penicillin should be continued. It also occurs in leptospirosis and relapsing fever.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.