Background Familial Hemophagocytic lymphohistiocytosis (fHLH) categorized as FHL2 (PRF1), FHL3 (UNC13D), FHL4 (STX11), and FHL5 (STXBP2) encoding for Perforin, Munc13-4, Syntaxin11, and Syntaxin binding protein 2, respectively. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population.

Objectives To delineate clinical and laboratory features of late onset familial Hemophagocytic Lymphohistiocytosis.

Methods A 12-years-old well nourished sick looking boy, born to a non-consanguineous parents with normal birth, development and immunization history with uneventful past presented to us with 6 days history of high fever, cough, breathing difficulty and severe headache. He had occasional vomiting, abdominal pain, polyarthragia & chest pain from last 10 days. Mother also had given history of throat pain, backache & some non-specific papular rashes over face before the onset of fever. His vitals were normal. Examination revealed faint diffuse fixed erythematous rash all over the body, pallor, icterus and hepatosplenomegaly. Musculoskeletal examination was unremarkable.

Lab evaluation revealed HB 8.9gm%, TLC 4700/cumm with neutrophils 40% and lymphocytes 56% with 8-9% activated lympocytes. Further evaluation showed low ESR 6mm/hr, fibrinogen 97mg% and albumin 2.2 gm% with elevated CRP 40mg/L, ferritin 2000ng/ml, LDH 658IU/L, SGPT 110IU/L, SGOT 221 IU/L, total bilirubin 6mg%, D-dimer 4355 ng:EFU/ml and Triglycerides 441mg%. His blood, urine, CSF and bone marrow cultures were sterile for endemic bacterial and viral infections in our area. His EBV PCR, CoVID RT PCR and CoVID antibody (Total & IgG) test were negative. His immunoglobulin leves were normal. HRCT Chest showed bilateral mild-moderate plural effusions, mild interstitial thickening in both the lower lobes, few fibrotic opacities & old areas of consolidation bilaterally. 2D echo showed mild pericardial effusion. Bone marrow examination showed Hypercellular marrow with iron depletion and occasional hemophagocytosis with CD8 T lymphocytes proliferation (55.2%) and double positive CD4 & CD8 (1.2%). He was initially commenced on supportive therapy, oxygen & intravenous antibiotics.

In view of most probable non-infectious, non- malignant hemophagocytic lymphohistiocytosis, he was finally given intravenous immunoglobulin (2gm/kg) and intravenous pulse methylprednisolone (30mg/kg). He responded well to above regimen within 3 days. He was discharged with tapering steroids over few weeks.

Clinical exome by NGS revealed Homozygous Mutation in STXBP2 gene Intron 14, c.1280-1G>C (3’ Splice Site) His parents has been counselled for hematopoietic stem cell transplantation and their decision is still pending.

Results We compared our patietnt with a reference to the largest Indian series of pediatric HLH¹.

Conclusion Primary HLH type 5 can present first time during childhood and adolescence. Any child presenting with unexplained HLH features should undergo genetic analysis irrespective of person’s past and family history.

References [1]Front. Immunol., 05 March 2021, The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India, Snehal Shabrish, Madhura Kelkar, Reetika Malik Yadav

Acknowledgements Dr Jay Virani, Dr Vinod Bhadukiya, Dr Sameer Dhami

Disclosure of Interests None declared