ABSTRACT
The incorporation of next generation sequencing into routine immunological practice has enabled the identification of novel inborn errors of disease, helped define new categories of immune deficiency and extended the clinical spectrum associated with many long-recognised diseases. The family of EBV (Epstein Barr Virus)-sensitive primary immune deficiencies is one such group and in this paper we describe three families: two with X-linked lymphoproliferative disease type-1 (XLP-1) and one with deficiency of Interleukin-2 Inducible T-cell Kinase (ITK). Both diseases have a wide range of clinical manifestations and are united by an exquisite predisposition to EBV, dysgammaglobulinemia, hemophagocytic lymphohistiocytosis, and lymphoma. We detail our approach to diagnosis, treatment, and risk stratification in these diseases where both clinicians and patients must grapple with constant uncertainty.
Subject(s)
Immunologic Deficiency Syndromes/complications , Lymphoproliferative Disorders/therapy , Protein-Tyrosine Kinases/deficiency , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphoproliferative Disorders/genetics , Male , Middle Aged , Protein-Tyrosine Kinases/genetics , Retrospective StudiesABSTRACT
The clinical manifestations of HIV disease in children affect multiple organ systems. The severity of each manifestation varies by organ system and can be related in many cases to multifactorial causes, namely HIV replication in affected tissue, concomitant opportunistic infection of the organ, effect of concurrent immunodeficiency or autoimmune mechanisms on the organ, or adverse end-organ drug effect (primary HIV therapy or prophylaxis regimens). More information is needed to understand the pathogenesis of the systemic effect of HIV on different organ systems, especially the CNS. Most clinicians hope that advances in therapeutic interventions for primary HIV will halt the progression of the organ-specific manifestations that have been outlined in this article, but such potent therapies will probably have their own unique and new effects on HIV-infected organ systems. Vigilance for organ-specific manifestations in the era of HAART is imperative to provide the best clinical outcome for HIV-infected children.
