Jarisch–Herxheimer Reactions with artemether/lumefantrine: an uncommon side effect of anti-malarial medications

Background: The Jarisch–Herxheimer reaction (JHR) was a nonspecific adverse effect manifested by fever, chills, headache, myalgia, and exacerbations of skin rash that’s firstly described with anti-spirochetes medications and later with fluoroquinolones, cephalosporins, meropenem, and tetracyclines but not with antiparasitic drugs. Herein we reported JHR in a young Sudanese male due to antimalarial medications with good outcomes. Case Presentation: A 27-year-old Sudanese man presented with malaria-like symptoms and was given an oral artemisinin combination. However, within 8 h, the patient developed high-grade fever, chills, rigors, recurrence of the headache, tachycardia, myalgia, and tachypnoea, which was diagnosed as a JHR. The drug was temporarily stopped, the patient was hydrated, and an antipyretic was given, then the drug was restarted with a good response. Viral screening and syphilis tests were negative while blood tests showed leukocytosis, lymphopenia, and left shift in granulocytes. Discussion: In this case, the patient received Coartem 80/480 (artemether 80 mg/lumefantrine 480 mg). Eight hours after starting treatment, his fever dropped to 37.8°C, with other symptoms improving. Surprisingly at 8 h, the patient developed a second fever of 39.4°C, with chills, headache, tachycardia, a pulse rate of 103, myalgia, and hyperventilation. This is comparable with Koefoed’s case, where the patient received Fansidar (sulfadoxine/pyrimethamine). His JHR started 10 h later, indicated by the second rise in temperature. Conclusion: JHR can occur with antimalarial medications, most commonly by non-specific symptoms and worsening of pre-existing skin lesions; this requires a high clinical susceptibility, particularly within the first 24 h, with treatment discontinuation and hydration as the mainstay of management, with good outcomes.