Successful prevention of severe infection in Japanese siblings with interleukin-1 receptor–associated kinase 4 deficiency
Article Outline
To the Editor:
Three years ago, our group reported a Japanese patient with interleukin-1 receptor–associated kinase 4 (IRAK4) deficiency.1 Subsequently, this patient's younger siblings, a 3-year-old brother and a 32-month-old sister, were born with the same IRAK4 gene mutation, with absence of tumor necrosis factor-α and interleukin-6 production from mononuclear cells in response to lipopolysaccharide. To date, we have successfully prevented severe infections in these 2 patients. Here we report additional information on their favorable clinical course.
To prevent bacterial infections, the children were given oral prophylactic antibiotics beginning at age 2 months, followed by Ig substitution (200 mg/kg/month) from age 6 months to 12 months; heptavalent-conjugate pneumococcal vaccine twice, at age 12 and 14 months; and 23-valent polysaccharide pneumococcal vaccination at age 2 years. When they had infection, pyrexia was not seen. In an effort to prevent bacterial infections, prophylactic intravenous antibiotics were given for common cold symptoms, even when not associated with fever or elevated serum C-reactive protein level. During treatment, the children's titers of anti–Streptococcus pneumoniae IgG2 antibody were elevated, and they remained free of severe infections, unlike other patients with IRAK4 deficiency.
Although the first-born child in this family died due to pneumococcal meningitis before a diagnosis of IRAK4 deficiency was made, his 2 siblings likely benefited from aggressive preventive measures in the first few years of life. Previous reports indicate that children with IRAK4 deficiency battle severe bacterial infections uo to age 3 years, with milder infections occurring after age 4 or 5 years.2, 3 Acquired immunity through aggressive preventive care may compensate for the poor innate immune response in these children, allowing time to develop immune maturity with age. Evidently, preventing bacterial infection during the most susceptible years is of critical importance when caring for patients with IRAK4 deficiency.
References
- Delayed separation of the umbilical cord in two siblings with interleukin-1 receptor–associated kinase 4 deficiency: rapid screening by flow cytometry. J Pediatr. 2006;148:546–548
- Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science. 2003;299:2076–2079
- Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity. J Exp Med. 2007;204:2407–2422
PII: S0022-3476(09)00670-2
doi:10.1016/j.jpeds.2009.07.042
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