Pneumococcal meningitis in a patient with IL-1 receptor–associated kinase-4 deficiency: A case of failed prophylaxis

IL-1 receptor-associated kinase-4 (IRAK-4) is a receptor-associated protein kinase involved in toll-like receptor and IL-1 receptor signaling that leads to the production of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-[alpha], IFN-[alpha]/β, and IFN-λ).1 Deficiencies in IRAK-4 signaling can lead to invasive pyogenic bacterial infections, skin infections, and recurrent upper respiratory tract infections.2 Patients with an IRAK-4 deficiency have a weakened ability to mount fever early in infection, and the poor production of IL-6 leads to lower than expected C-reactive protein levels.2 Some patients have impaired antibody production after polysaccharide and protein vaccines and reduced memory (IgM+, IgD+CD27+) B cells, and many of those who do respond to vaccines fail to sustain these responses long term.3,4 The risk for invasive infection seems to gradually decline during adolescence, likely due to the compensatory response of the adaptive immune system.3 Prophylaxis with immunoglobulin therapy may be necessary at least until the adaptive immune system has developed.1 Recommended therapy to prevent invasive bacterial infections in patients with IRAK-4 deficiency includes prophylaxis with penicillin and/or cotrimoxazole, antipneumococcal immunization, and replacement-dose immunoglobulin (400 mg/kg every 3-4 weeks).1,5 We present a 5-year-old white boy with IRAK-4 deficiency. Age (mo) Infection Pathogen Treatment Newborn Pneumonia None isolated Intravenous ampicillin and gentamicin for 10 d 4 Retropharyngeal abscess Enteric gram-negative rods, Pseudomonas species, Neisseria species, Haemophilus parahemolyticus Intravenous, oral clindamycin 16 Pneumonia with effusion None isolated Effusion drained by thoracentesis, treated with intravenous cefotaxime followed by oral cefdinir 22 Liver abscesses Methicillin-resistant Staphylococcus aureus, Streptococcal pneumonia Percutaneous drainage by interventional radiology; intravenous nafcillin for 7 wk, followed by oral cephalexin for 2 mo 22 Pneumonia None isolated Nafcillin 32 Liver abscesses Methicillin-resistant S aureus, S pneumonia Percutaneous drainage by interventional radiology; intravenous cefazolin for 12 wk, followed by oral cephalexin 34   Replacement immunoglobulin started 57 Meningitis S pneumonia Intravenous Rocephin and vancomycin for 1 mo followed by 4 wk of treatment with amoxicillin with clavulanic acid 59   High-dose weekly immunoglobulin started 66 Otitis media Pseudomonas aeruginosa,