Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Clinical Background
Human primary immunodeficiencies that are associated with impaired innate immunity (nuclear factor kappa B signaling) are ectodermal dysplasia (X-linked or autosomal dominant) and interleukin-1 receptor associated kinase 4 (IRAK-4) deficiency.
Epidemiology
- Incidence
- Ectodermal dysplasia - 1/100,000 births
- IRAK - rare; <30 affected individuals worldwide as of 2006
Inheritance
- All are familial syndromes
- Ectodermal dysplasia with immunodeficiency (EDA)
- X-linked inheritance with NEMO mutation (AD-EDA) - also called hypohidrotic ectodermal dysplasia
- IRAK-4 deficiency
- Autosomal recessive inheritance
Pathophysiology
- IRAK
- IRAK 4 - plays an essential role in Toll-like receptor and IL-1 receptor mediated signaling
- Broad defect in nuclear factor kappa B signaling with impaired Toll-like receptor function
- Toll-like receptors function as recognition factors for microbial and viral ligands, enabling innate immunity to induce appropriate pathways to prevent infection
- EDA
- Abnormal development of 2 or more structures derived from the ectodermal layer
- Most common is hypohidrotic dysplasia
- Patients with these defects have otherwise normal immune systems and no difficulty with viral or other bacterial infections
Clinical Presentation
- Severe recurrent infections occur in both deficiencies
- EDAs (AD and XL)
- Abnormal teeth (anodontia, hypodontia or cone/peg-shaped), hypohidrosis, hypotrichosis, cranial abnormalities, sparse hair
- Particular susceptibility to encapsulated bacterial infections
- Failure to thrive
- IRAK-4
- Normal appearance
- Particular susceptibility to S. pneumoniae and S. aureus
- All invasive infections occur before age 14
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Diagnosis
Diagnosis
- Laboratory testing
- Screen for other immunodeficiencies including immunoglobulin levels, complement, neutrophil function (see algorithms - Immunodeficiency Evaluation for Chronic Infections Testing in Adults and Immunodeficiency Evaluation for Chronic Infections Testing in Children)
- If hypogammaglobulinemia is present, consider EDA
- If all screening tests are normal, order IRAK-4 and toll-like receptor function testing
Differential Diagnosis
- Neutropenic syndromes
- Chronic granulomatous disease
- Chédiak-Higashi
- Job syndrome
- LAD deficiency
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Interleukin-1-Receptor-Associated Kinase-4 (IRAK-4) Deficiency Screen
|
| ARUP #: 0051393 |
| Methodology: Cell Culture/Multi-Analyte Fluorescence Detection
|
| Use: Diagnose IRAK-4 deficiency in patients negative for other immunodeficiencies |
| Limitations: |
| Follow-up:
|
| Test name: Toll-Like Receptor Function Assay
|
| ARUP #: 0051589 |
| Methodology: Cell Culture/ Multi-Analyte Fluorescence Detection
|
| Use: Assist in diagnosis of innate immunodeficiencies |
References
General References
Hernandez M, Bastian JF. Immunodeficiency in childhood. Curr Allergy Asthma Rep.
2006;
6(
6):
468-474.
Immune Deficiency Foundation (Accessed 30 May 2008) Ku CL, Yang K, Bustamante J, Puel A, von Bernuth H, Santos OF, Lawrence T, Chang HH, Al-Mousa H, Picard C, Casanova JL. Inherited disorders of human Toll-like receptor signaling: immunological implications. Immunol Rev.
2005;
203:
10-20.
Picard C, Puel A, Bustamante J, Ku CL, Casanova JL. Primary immunodeficiencies associated with pneumococcal disease. Curr Opin Allergy Clin Immunol.
2003;
3(
6):
451-459.
Picard C, von Bernuth H, Ku CL, Yang K, Puel A, Casanova JL. Inherited human IRAK-4 deficiency: an update. Immunol Res.
2007;
38(
1-3):
347-352.
Puel A, Picard C, Ku CL, Smahi A, Casanova JL. Inherited disorders of NF-kappaB-mediated immunity in man. Curr Opin Immunol.
2004;
16(
1):
34-41.
Suzuki N, Saito T. IRAK-4--a shared NF-kappaB activator in innate and acquired immunity. Trends Immunol.
2006;
27(
12):
566-572.
Yavuz I, Baskan Z, Ulku R, Dulgergil TC, Dari O, Ece A, Yavuz Y, Dari KO. Ectodermal dysplasia: Retrospective study of fifteen cases. Arch Med Res.
2006;
37(
3):
403-409.
Medical Reviewers
Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah
Comprehensive Review: May 2008
Last Update: July 2008
