Corticosteroids as adjunctive therapy in patients with acute/subacute paracoccidioidomycosis presenting a severe paradoxical inflammatory reaction: Two case reports and literature review

Paradoxical inflammatory reactions, similar to Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV, have been occasionally reported in leprosy, tuberculosis, certain immunosuppressive conditions, and Paracoccidioidomycosis (PCM), among others. This report presents the clinical data and outcomes of two PCM cases in which the patients developed a severe inflammatory reaction following antifungal therapy, with subsequent improvement after adjunctive corticosteroid use. Both patients were adults with acute/subacute PCM who experienced clinical worsening after starting liposomal amphotericin B, with fever, anasarca, jaundice, and exacerbation of pre-existing symptoms. After excluding other infections, intravenous hydrocortisone was administered, resulting in rapid improvement. Corticosteroids were tapered after two to three weeks, and both patients continued outpatient follow-up while receiving itraconazole. Few similar PCM cases have been described in the literature, and they reported comparable outcomes. Its exact mechanism remains unclear, but may be immune-mediated. Reporting additional cases is essential to better establish the true incidence of this reaction and to strengthen the evidence supporting the benefit of corticosteroids as an adjunctive therapy.