Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder Complicated by Septic Shock in Activated PI3Kδ Syndrome: A Pediatric Case Report and Literature Review.
This case report describes a 17-year-old with PIK3CD-associated activated PI3Kδ syndrome, EBV-positive B-cell lymphoproliferative disease of uncertain pathological classification, and subsequent septic shock with metagenomically detected gram-negative pathogens and antimicrobial-resistance genes.
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This case report describes a 17-year-old with PIK3CD-associated activated PI3Kδ syndrome, EBV-positive B-cell lymphoproliferative disease of uncertain pathological classification, and subsequent septic shock with metagenomically detected gram-negative pathogens and antimicrobial-resistance genes.
Research significance
The reported case supports the clinical importance of adequate tissue sampling, EBV and microbiological surveillance, and multidisciplinary management in APDS-associated lymphoproliferation; it is reasonable but unproven to hypothesize that earlier diagnostic clarification and infection-guided treatment could improve therapeutic selection and reduce infectious complications.
Source abstract
Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare inborn error of immunity caused by gain-of-function variants in PIK3CD and characterized by recurrent infections, lymphoproliferation, and impaired viral control. We report a 17-year-old male with a heterozygous PIK3CD c.3061G > A (p.E1021K) variant who presented with progressive edema, extensive hypermetabolic lymphadenopathy, splenomegaly, and Epstein-Barr virus (EBV) DNAemia. A core needle biopsy of the right inguinal lymph node demonstrated an immunodeficiency-associated EBV-positive B-cell lymphoproliferative disorder with extensive monotypic plasmacytoid differentiation. Because the biopsy contained limited mature B-cell tissue, the pathological findings favored a polymorphic B-LPD although EBV-positive diffuse large B-cell lymphoma with plasmacytic differentiation could not be excluded. The patient received anti-B-cell-directed therapy and supportive treatment. He was subsequently readmitted with septic shock and acute respiratory distress syndrome. Blood metagenomic next-generation sequencing detected Escherichia coli and Klebsiella pneumoniae, together with antimicrobial-resistance genes including blaNDM. Despite intensive antimicrobial and organ-supportive treatment, the patient remained critically ill and was discharged at his family's request for transfer to a local hospital; his subsequent outcome was unavailable. This case highlights the diagnostic difficulty of classifying EBV-positive B-cell proliferations using limited biopsy tissue in APDS and the competing risks of lymphoproliferative disease and severe infection. Adequate tissue sampling and pathological characterization, close microbiological surveillance, and individualized multidisciplinary management are essential in this setting.