Written by Alexander Turner and Ketan Patel
Spoon Feed
One in four patients had a Jarisch-Herxheimer reaction* (JHR) when treating syphilis with benzathine penicillin G. The JHR was associated with secondary syphilis, HIV-negative status, and a better treatment response at six months.
Chills, fevers, and victory – surviving the Jarisch-Herxheimer rollercoaster
With rates of syphilis on the rise, we see an increasing number of patients who receive treatment for this disease, and knowing more about symptoms that may develop from benzathine penicillin G treatment is an important step in patient care.
This secondary analysis of a phase 4 RCT examined the incidence of JHR after benzathine penicillin G treatment in adults with early syphilis. Among 249 participants, JHR occurred in 23.7%, with symptom onset at a median of 4.9 hours and lasting 12.8 hours. JHR was more common in secondary syphilis (AOR 2.91, 95%CI 1.51-5.61) and less frequent in individuals with HIV (AOR 0.49, 95%CI, 0.26-0.94). Serologic treatment response at six months was higher in those with JHR (84.7% vs. 68.9%; P = .01).
This study gives valuable information on JHR in early syphilis treatment, but the study population was narrow, with a high prevalence of young male subjects. Larger validation studies including all stages of syphilis, a higher female cohort, pregnancy state, and broader age groups would help generalizability.
How will this change my practice?
Practicing in Las Vegas, we have a high prevalence of syphilis in our community. Knowing that JHR was associated with a higher treatment response at six months, plus having background knowledge on median time of onset, typical symptoms, and duration helps with counseling when initiating treatment.
*JHR – transient fever, chills, or worsening rash after antibiotic treatment of syphilis or other spirochetes.
Source
Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Feb 3;8(2):e2459490. doi: 10.1001/jamanetworkopen.2024.59490. PMID: 39946129
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