Snapshot An 8-year-old boy is brought to his pediatrician for easy bruising. On physical exam, he is found with petechiae and purpura in multiple areas over his body, as well as bruises over his arms. Eczematous patches are also found on his flexural surfaces. Laboratory results reveal thrombocytopenia to 30,000/mm3. Further questioning reveals a past medical history of multiple hospital stays due to pneumonia and otitis media infections as well as recurrent epistaxis. Introduction Primary immunodeficiency disorder of B and T cells Pathogenesis mutation in WAS gene encoding Wiskott-Aldrich syndrome protein (WASp) impaired actin cytoskeleton results in defective T cell signalling and interactions with APCs also impairs phagocytosis and chemotaxis loss of cellular and humoral response Genetics X-linked recessive To remember (WATER) Wiskott Aldrich Thrombocytopenic purpura Eczema Recurrent infections Presentation Symptoms/physical exam recurrent bacterial, viral, fungal infections frequency increases with age bacterial agents: Streptococcus pneumonia, Haemophilus influenza, Neisseria meningitides viral agents: varicella and CMV fungal infections: Candida albicans thrombocytopenia recurrent bleeding, especially in first days of life petechiae purpura easy bruising hematemesis epistaxis hematuria chronic eczema hepatosplenomegaly common Evaluation Serologies ↓ number of T and B cells ↓ to normal IgG, IgM ↑ IgE, IgA Labs thrombocytopenia usually 20,000/mm3 - 50,000/mm3 Gene sequence analysis of WAS essential to confirm diagnosis Differential Diagnosis Severe combined immunodeficiency Hyper IgE syndrome (also with eczema) Atopic dermatitis Treatment Antibiotics IVIG Hematopoietic stem cell transplantation only curative treatment Prognosis, Prevention, and Complications Prognosis reduced life expectancy (see complications below) bleeding is main cause of death Complications increased risk of autoimmune diseases malignancies (lymphomas, leukemias), usually fatal infections complications may lead to early death chronic eczema superinfection