Recognizing haemophagocytic lymphohistiocytosis in an HIV patient with disseminated tuberculosis: not every fever is sepsis

Abstract

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition that causes hyperinflammation, extensive tissue destruction, multi-organ failure (MOF) and death due to uncontrolled activation and proliferation of T cells and macrophages. HLH can be primary (genetic) and secondary (acquired). Primary HLH occurs due to genetic mutations, and secondary HLH is often triggered by autoimmune diseases, infections (commonly viral, bacterial and parasites) and malignancies, such as lymphoma. We report a case of secondary HLH in a 43-year-old man with an untreated human immunodeficiency virus (HIV) infection and newly diagnosed disseminated tuberculosis who was admitted to the acute medicine ward with some non-specific gastrointestinal symptoms. Nevertheless, he was treated with guideline-directed antibiotics, but his condition failed to improve with persistent high-grade fever, haemodynamic instability, splenomegaly, pancytopenia, transaminitis and hyperferritinaemia (ferritin: >18,000 μg/L). Hence, the multidisciplinary team (MDT) initiated a workup including the Haemophagocytic Lymphohistiocytosis Diagnostic Score (HScore) and bone marrow biopsy, along with viral screening, tuberculosis (TB) tests and computed tomography (CT) of the chest, abdomen and pelvis, followed by bronchoscopy. The clinical diagnosis of HLH was established based on the highly supportive clinical and laboratory criteria, as reflected by an extremely high HScore (272), despite the absence of haemophagocytosis on bone marrow biopsy. Later, the bronchial washing confirmed the detection of Mycobacterium tuberculosis. Our rheumatology, haematology and acute medicine team consensually agreed to start intravenous (IV) pulse methylprednisolone for three days, followed by antiretroviral and anti-tubercular regimens. This case underscores the diagnostic challenge of HLH in untreated patients with HIV and disseminated TB, where the clinical manifestations can resemble sepsis, cytokine storm or systemic inflammatory response syndrome (SIRS). Ultimately, early identification and timely intervention with immunosuppressive therapy are crucial for the favourable outcome of patients with HLH.