ABSTRACTIntroduction and importance: Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease caused by the overactivation of tissue macrophages in response to environmental factors. Because HLH has many clinical symptoms with malaria, which is the underlying cause, identifying the condition can be difficult.Case presentation: We present a rare case of HLH triggered by malaria in a 15-year-old male patient of paroxysmal cold hemoglobinuria (PCH), which developed as a response to latent syphilis. The patient presented with fever and hematuria, diagnosed with malaria by Plasmodium Falciparum; he was started on Artesunate with anemia correction and cold avoidance. After antimalarial therapy, the patient’s clinical condition worsened, and he met the criteria for HLH. Treated with IV dexamethasone and injection epokine under strict surveillance the patient showed complete recovery.Clinical Discussion: Pakistan has reported an only case of malaria with Plasmodium vivax and HLH. Nonetheless, several instances of Plasmodium falciparum and vivax infections have been documented in China and India. Patients in each of these situations have a decent prognosis. The fatality rate from HLH is not widely known, however secondary HLH is fatal without treatment.Conclusion: This report aims to alert physicians, about the complication of HLH in malaria and to present a model approach to diagnose and treat it when linked to PCH.Keywords: Paroxysmal cold hemoglobinuria, hemophagocytic lymphohistiocytosis, malaria, case report1 INTRODUCTION Hemophagocytic lymphohistiocytosis (HLH) is a sporadic syndrome of pathologic immune activation caused by a variety of environmental triggers such as infection, cancer, and rheumatologic disorders. Because of the HLH syndrome’s rarity, diversity, and complexity, diagnosis is difficult [1]. Malaria, a vector-borne disease caused by Plasmodium species is a rare cause of HLH, hence it is difficult to diagnose due to significant overlap in clinical features and laboratory findings between these two entities, which can be complicated by pre-existing paroxysmal cold hemoglobinuria (PCH) rarely found in the literature [2]. PCH is a type of autoimmune hemolytic anemia (AIHA) caused by atypical IgG autoantibodies that bind to their target RBC antigen and fix complement at 4 °C. After complement activation, cold-reactive antibodies primarily cause intravascular hemolysis producing symptoms including hemoglobinuria, pallor, jaundice after cold exposure [3]. We present the first reported case of HLH in a 15-year-old patient with PCH triggered by acute febrile illness secondary to malaria. This case underscores the importance of considering a broad differential diagnosis in patients presenting with fever and hemolysis, particularly in areas with a high prevalence of malaria. Additionally, it highlights the need for prompt recognition and management of HLH, as it can have life-threatening complications if left untreated.
