Shigella sonnei meningitis due to interleukin-1 receptor-associated kinase-4 deficiency: first association with a primary immune deficiency

Clin Infect Dis. 2005 May 1;40(9):1227-31. doi: 10.1086/428733. Epub 2005 Mar 31.

Abstract

Background: Inherited interleukin-1-receptor-associated kinase-4 (IRAK-4) deficiency is a recently described immunodeficiency associated with pyogenic bacterial infections and a poor inflammatory response. Shigella sonnei is generally associated with outbreaks of rectocolitis in developed countries, but systemic illnesses have occasionally been reported. An underlying primary immunodeficiency has not been found in such cases before now.

Methods: We report the clinical and immunological features of a patient with IRAK-4 deficiency who has a history of systemic shigellosis in addition to other infections.

Results: The patient has a history of Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa infections during childhood and an episode of S. sonnei septicemia and meningitis at 10 years of age. This patient's history contrasted with that of other individuals infected concurrently by the same organism. Of note, these episodes were not accompanied by acute phase responses in our patient. Subsequently, the patient has had more episodes of staphylococcal disease, but no systemic illnesses. The patient is now 30 years old and has been doing well since prophylactic antibiotic treatment was stopped 4 years ago.

Discussion: To our knowledge, this is the first report of a case of systemic shigellosis in a person with a primary immunodeficiency, expanding the spectrum of infections associated with IRAK-4 deficiency. Thus, immunity mediated by IRAK-4 seems to be crucial for both the containment of and the inflammatory response to S. sonnei infection in the intestinal mucosa. IRAK-4 deficiency and related disorders should be considered in patients with systemic shigellosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Dysentery, Bacillary / complications
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Meningitis, Bacterial / cerebrospinal fluid
  • Meningitis, Bacterial / drug therapy
  • Meningitis, Bacterial / etiology
  • Meningitis, Bacterial / microbiology*
  • Protein Serine-Threonine Kinases / deficiency*
  • Protein Serine-Threonine Kinases / genetics*
  • Shigella sonnei / isolation & purification*
  • Shigella sonnei / pathogenicity
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-10
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Interleukin-1 Receptor-Associated Kinases
  • Protein Serine-Threonine Kinases