Severe Adverse Reaction to the Use of 3hp in the Treatment of Latent Tuberculosis Infection: A Case Report

The treatment of latent infection by Mycobacterium tuberculosis (LTBI) is one of the main strategies for tuberculosis elimination in Brazil. The weekly rifapentine plus isoniazid regimen (3HP) was introduced in 2021, with efficacy similar to previously established regimens and advantages such as higher treatment completion rates and safety. Adverse events (AEs) associated with 3HP are mostly mild and self-limited. Flu-like syndrome and other systemic hypersensitivity reactions are known AEs of 3HP and include symptoms such as fever, chills, malaise, tachycardia, flushing, conjunctivitis, skin symptoms (rash, facial edema), respiratory and gastrointestinal symptoms. These are generally associated with intermittent use of rifamycins. Severe reactions with hypotension, syncope, and need for hospitalization are rare. We present a case of a severe adverse event requiring hospitalization in a patient using 3HP. A 35-year-old male with psoriasis, indicated for immunobiologic therapy (anti-IL23), and reactive IGRA, without other comorbidities. 3HP was initiated on 04/02/25. After three weeks, he reported onset of fever (38°C) and nausea on the day following medication intake. In the sixth week, one hour after the regimen, he developed fever, diffuse maculopapular rash, and tremors. He progressed with facial edema, ocular erythema, nausea, dyspnea, chest pain, and syncope. At the emergency department, he was hypotensive and tachycardic, with elevated transaminases (AST 149 and ALT 299). Corticosteroid therapy was administered and 3HP was discontinued. After clinical improvement, reintroduction of isoniazid (INH) was attempted in a hospital setting. The patient presented the same symptoms, and the drug was discontinued after the second dose. Treatment of LTBI with rifampicin was then attempted, without complications. The symptoms presented are consistent with flu-like syndrome and systemic hypersensitivity reaction. In the medical literature, flu-like symptoms have been reported in approximately 3%–4% of patients using 3HP, and hypersensitivity reactions in 1%. It is concluded that the reported adverse events were secondary to INH, present in the regimen. Although INH may be related to drug fever, flu-like syndrome and hypersensitivity reactions are rarely reported. As LTBI treatment becomes widely used, awareness of adverse drug effects, even rare ones, is important for earlier diagnostic suspicion of severe involvement.