Pseudomonas Meningitis and Intracranial Hemorrhage in IRAK-4 Deficiency

Abstract

Interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immune deficiency of the innate immune system. Children with this condition are susceptible to life-threatening bacterial infections. IRAK-4 deficiency results in reduced or absent systemic features of inflammation despite overwhelming infection. We present 2 siblings who died in infancy after rapidly progressive Pseudomonas sepsis and meningitis. There was diagnostic uncertainty in the firstborn infant because of significant intracranial hemorrhages. This was confounded by a failure to mount an inflammatory response. As such, it was difficult to distinguish between possible nonaccidental injuries and an infectious cause. Perimortem genetic analysis of the second-born infant identified a known mutation in IRAK-4. We intend to raise awareness of IRAK4 deficiency, highlight the importance of considering primary immune deficiencies in the differential of unusually severe infection, document progressive intracranial radiologic changes seen in overwhelming Pseudomonas meningitis and discuss the differences in the radiologic features seen in abusive head trauma within this age group.

Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis

“…Considering accumulating observations in patients with IRAK-4 de ciency, mainstay treatment for this disease includes immunoglobulin replacement by IV (IVIG) or subcutaneous (SCIG) along with prophylactic antibiotic therapy [38]. In the absence of current information, IgG replacement therapy may need to last a lifetime [15]. The use of empiric antibiotics in the treatment of IRAK4-de cient patients calls for consideration of potential antibiotic resistance in addition to the requirement for broad-spectrum coverage, which covers not only common organisms, such as S. pneumococcus and S. aureus, but also, some uncommon gram-negative strains, such as P. aeruginosa.…”

“…Furthermore, P. aeruginosa infection coupled with a poor acute phase may be the initial sign of a potential primary immune de ciency (PID), especially defects in TLR1 signaling pathways such as IRAK-4 de ciency [10,14]. Actually, children with P. aeruginosa sepsis have been identi ed along with IRAK-4 de ciency in a few cases [10,13,15].…”