The Diverse Presentation of Pediatric Hemophagocytic Lymphohistiocytosis in a Philippine Tertiary Hospital: A Case Series

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome with high mortality in children. In resource-limited settings with high infectious burdens, the diagnosis is particularly challenging as HLH masquerades as severe, common infections. This case series describes the presentation, triggers, and outcomes of pediatric HLH in the Philippines, highlighting the unique diagnostic and management hurdles. A retrospective, descriptive case series was conducted at a Philippine tertiary hospital. We reviewed the medical records of four pediatric patients (aged 2-18 years) diagnosed with HLH based on established clinical and laboratory criteria. Four cases were identified with a striking diversity of infectious triggers: SARS-CoV-2, Typhoid Fever, Disseminated Histoplasmosis, and Toxoplasmosis. All patients presented with the classic triad of prolonged fever (8 days to 6 months), hepatosplenomegaly, and significant cytopenias. Laboratory confirmation was marked by profound hyperferritinemia (peak 18,180 ng/mL), hypertriglyceridemia (peak 1,039 mg/dL), and elevated LDH, corresponding to high H-Scores (151-319). A critical observation was the tempo of presentation: viral and bacterial triggers caused hyperacute illness (<2 weeks), while the fungal trigger (Histoplasmosis) presented as a chronic, 6-month indolent fever, significantly delaying diagnosis. Management involved trigger-directed antimicrobials and varied immunomodulation. Two patients received aggressive HLH therapy (IVIG, steroids, etoposide, cyclosporine), one received IVIG alone, and one received only antifungals. Outcomes were heterogeneous: two patients improved, one was discharged against medical advice following antifungal therapy, and one died despite maximal therapy. The mortality underscores the syndrome's ferocity, while the discharge against medical advice reflects profound socio-economic challenges in this setting. This series underscores that HLH must be a primary diagnostic consideration in any child with persistent fever and cytopenias in high-infection burden regions. The varied infectious triggers and clinical courses demand a high index of suspicion. Optimal management requires a dual, simultaneous strategy: aggressive treatment of the underlying infection and timely, protocol-driven immunomodulation to control the cytokine storm. These findings highlight the need for improved diagnostic awareness and adapted treatment protocols in resource-limited environments.