Clinical spectrum and laboratory correlates of concurrent hemophagocytic lymphohistiocytosis and toxoplasmosis: a systematic review

Concurrent hemophagocytic lymphohistiocytosis (HLH) and toxoplasmosis represent a rare but clinically significant overlap, posing diagnostic and therapeutic challenges. A comprehensive understanding of their combined clinical and laboratory features is essential for improving patient outcomes. This systematic review aims to characterize the clinical presentations and laboratory findings of patients diagnosed with simultaneous HLH and toxoplasmosis, based on published case reports. A comprehensive literature search was conducted across the PubMed, Web of Science, ScienceDirect, and Google Scholar databases up to June 2025. We included case reports and series describing patients simultaneously affected by HLH and toxoplasmosis, adhering strictly to predefined inclusion criteria to ensure relevance and quality. From 13 eligible studies, 13 case reports involving 14 patients were analyzed. The majority (79%) were male, with ages ranging from 26 to 58 years. Diagnostic approaches incorporated a combination of biochemical blood tests aligned with HLH criteria, bone marrow examinations, serological assays, and molecular techniques such as polymerase chain reaction (PCR). These investigations underscored significant laboratory correlates that aid in confirming the dual diagnosis. Recognizing toxoplasmosis as a potential trigger or coexisting infection in HLH is vital due to its intertwined immunopathology. The cytokine release induced by toxoplasmosis can precipitate or exacerbate HLH, particularly in immunocompromised individuals, leading to a spectrum of clinical manifestations. Enhanced awareness among clinicians and laboratory professionals is essential to facilitate timely diagnosis and tailored management, ultimately improving patient outcomes.