Age: 5.0
Sex: M
Vaccine: PPV
Symptoms: Convulsion, Deafness, Encephalomalacia, Immunoglobulin therapy, Lumbar puncture abnormal
Clinical narrative: This spontaneous literature report has been received from a physician via Sanofi Pasteur MSD as part of a business agreement concerning a 5-year-old boy with IRAK-4 deficiency. He was first hospitalized for 12 days shortly after birth due to pneumonia. At 4 months, he was hospitalized for a retropharyngeal abscess with cultures positive for enteric gram-negative rods, Pseudomonas specifies, Neisseria species, and Haemophilus parahemolyticus. At 16 months, he developed pneumonia with loculated effusion, but no organisms were isolated. In addition to these invasive infections, the patient also had multiple episodes of otitis media and sinusitis during his first 2 years of life. At 22 months of age, he presented with right upper quadrant pain and was found to have multiple liver abscesses and right middle lobe pneumonia. Abscesses were drained, and cultures were positive for methicillin-resistant Staphylococcus aureus and Streptococcus pneumonia (serotype unknown). After completing treatment for the liver abscess, he was started on prophylactic trimethoprim-sulfamethoxazole (2 mg/kg) once daily due to clinical evidence of functional antibody deficiency. He presented at 32 months of age with recurrence of the liver abscesses as well as a right-sided abdominal wall abscess. Abscesses were drained, and cultures were again positive for methicillin-resistant S. aureus. The initial immune evaluation at 22 months of age revealed normal immunoglobulin levels, normal T, B, and natural killer cell populations by flow cytometry, and normal T cell function based on mitogen assay. Oxidative burst, complement receptor 3 (CD11b/CD18) function, CHSO, and vaccine responses to tetanus and diphtheria were normal. These studies were repeated at when the patient was 32 months of age and were again were normal. Antibody production after pneumococcal vaccination was inadequate. After receiving 2 doses of PREVNAR-7 at 3 months and 9 months, respectively, vaccine responses at 11 months were low. PREVNAR-7 was administered at 23 months and again at 26 months, followed by PNEUMOVAX23 at 32 months of age. B-cell phenotyping revealed normal B-cell populations, including IgM+, IgD+, CD27+, B cells (16%). Due to a limited antibody response to vaccinations and continued infections despite receiving prophylactic antibiotics, replacement dose intravenous immunoglobulin (IV1G) (500 mg/kg monthly) was started at 34 months. The patient did well over the next 8 months, without significant infection, and was converted to subcutaneous immunoglobulin (Hizentra; CSL Behring), 120 mg/kg weekly. Adherence to Hizentra therapy was adequate over this time period based on reported compliance as well as adequate IgG levels measured over time. At 58 months of age, the patient presented with fever, vomiting, and mental status changes, and was diagnosed with pansinusitis and S pneumoniae (serotype 33 and nontypeable pneumococcus) meningitis diagnosed by lumbar puncture and was cerebrospinal fluid DNA PCR positive for S pneumonia. This hospitalization was complicated by bilateral severe hearing loss, encephalomalacia, and seizures. Prior immune evaluation had demonstrated normal adaptive immunity and neutrophil oxidative burst activity thus making disorders such as X-linked agammaglobulinemia, common variable immunodeficiency disorder, specific polysaccharide antibody deficiency, severe combined immunodeficiency, and chronic granulomatous disease (all in the initial differential diagnosis) unlikely. Due to the nature of invasive pneumococcal infection, innate immune dysfunction, specifically IRAK-4 deficiency, was considered. Additional information is expected.