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Should Newborns be Screened for Immunodeficiency? Lessons Learned from Infants with Recurrent Otitis Media

  • Otitis (David P. Skoner, Section Editor)
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Abstract

Recurrent otitis media in children is considered one of the warning signs of primary immunodeficiencies (PIDs), particularly antibody deficiencies. Infants who have the most serious and potentially lethal form of PID, severe combined immunodeficiency (SCID), sometimes present with recurrent otitis media. Most of the time, because of the severity of the immune defect, they develop more serious and systemic infections. SCID is distinct among the PIDs and considered a pediatric emergency. Diagnosing SCID during the newborn period is crucial because survival completely depends on early diagnosis and treatment. Mortality declines significantly if immune reconstitution is established before 3.5 months of age, particularly before severe infections have occurred. However, most patients are diagnosed after they have suffered chronic or recurrent infections and developed permanent sequelae. Without institution of population-based newborn screening, most infants will miss the opportunity to live a healthy life.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis. 1989;160(1):83–94.

    Article  PubMed  CAS  Google Scholar 

  2. Freid VM, Makuc DM, Rooks RN. Ambulatory health care visits by children: principal diagnosis and place of visit. Vital and health statistics. Series 13, Data from the National Health Survey. 1998;(137):1–23.

  3. Berman S, Byrns PJ, Bondy J, Smith PJ, Lezotte D. Otitis media-related antibiotic prescribing patterns, outcomes, and expenditures in a pediatric Medicaid population. Pediatrics. 1997;100(4):585–92.

    Article  PubMed  CAS  Google Scholar 

  4. Auinger P, Lanphear BP, Kalkwarf HJ, Mansour ME. Trends in otitis media among children in the United States. Pediatrics. 2003;112(3 Pt 1):514–20.

    Article  PubMed  Google Scholar 

  5. Lanphear BP, Byrd RS, Auinger P, Hall CB. Increasing prevalence of recurrent otitis media among children in the United States. Pediatrics. 1997;99(3):E1.

    Article  PubMed  CAS  Google Scholar 

  6. Skoner AR, Skoner KR, Skoner DP. Allergic rhinitis, histamine, and otitis media. Allergy Asthma Proc. 2009;30(5):470–81.

    Article  PubMed  Google Scholar 

  7. Chonmaitree T, Revai K, Grady JJ, Clos A, Patel JA, Nair S, et al. Viral upper respiratory tract infection and otitis media complication in young children. Clin Infect Dis. 2008;46(6):815–23.

    Article  PubMed  Google Scholar 

  8. Schwartz B, Giebink GS, Henderson FW, Reichler MR, Jereb J, Collet JP. Respiratory infections in day care. Pediatrics. 1994;94(6 Pt 2):1018–20.

    PubMed  CAS  Google Scholar 

  9. • Gould JM, Matz PS. Otitis media. Pedia Rev/Am Acad Pedia. 2010;31(3):102–16. This is an excellent review on pediatric otitis media.

    Article  Google Scholar 

  10. •• Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161–78. This is the most recent update on PIDs.

    Article  PubMed  CAS  Google Scholar 

  11. Stiehm RE. The four most common pediatric immunodeficiencies. Ad Exp Med Biol. 2007;601:15–26.

    Article  Google Scholar 

  12. Boyle JM, Buckley RH. Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol. 2007;27(5):497–502.

    Article  PubMed  CAS  Google Scholar 

  13. Bonilla FA, Geha RS. 12. Primary immunodeficiency diseases. J Allergy Clin Immunol. 2003;111(2 Suppl):S571–81.

    Article  PubMed  CAS  Google Scholar 

  14. •• Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S182–94. This is an updated summary of recent progress on PIDs.

    Article  PubMed  Google Scholar 

  15. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48.

    Article  PubMed  CAS  Google Scholar 

  16. Plebani A, Soresina A, Rondelli R, Amato GM, Azzari C, Cardinale F, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. 2002;104(3):221–30.

    Article  PubMed  CAS  Google Scholar 

  17. Vihinen M, Kwan SP, Lester T, Ochs HD, Resnick I, Valiaho J, et al. Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia. Hum Mutat. 1999;13(4):280–5.

    Article  PubMed  CAS  Google Scholar 

  18. Yong PF, Tarzi M, Chua I, Grimbacher B, Chee R. Common variable immunodeficiency: an update on etiology and management. Immunol Allergy Clin North America. 2008;28(2):367–86. ix-x.

    Article  Google Scholar 

  19. Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. 2007;44(Pt 2):131–9.

    Article  PubMed  Google Scholar 

  20. Boyle RJ, Le C, Balloch A, Tang ML. The clinical syndrome of specific antibody deficiency in children. Clin Exp Immunol. 2006;146(3):486–92.

    Article  PubMed  CAS  Google Scholar 

  21. Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625–55.

    Article  PubMed  CAS  Google Scholar 

  22. • Wilson NW, Hogan MB. Otitis media as a presenting complaint in childhood immunodeficiency diseases. Curr Allergy Asthma Rep. 2008;8(6):519–24. This article reviews the relationship between recurrent otitis media and PIDs.

    Article  PubMed  Google Scholar 

  23. • Urschel S. Otitis media in children with congenital immunodeficiencies. Curr Allergy Asthma Rep. 2010;10(6):425–33. This is a review on pediatric otitis media in PIDs.

    Article  PubMed  Google Scholar 

  24. Buckley RH. Primary immunodeficiency or not? Making the correct diagnosis. J Allergy Clin Immunol. 2006;117(4):756–8.

    Article  PubMed  Google Scholar 

  25. Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev. 2004;202:67–83.

    Article  PubMed  CAS  Google Scholar 

  26. Roberts JL, Lengi A, Brown SM, Chen M, Zhou YJ, O’Shea JJ, et al. Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood. 2004;103(6):2009–18.

    Article  PubMed  CAS  Google Scholar 

  27. Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T(−)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998;20(4):394–7.

    Article  PubMed  CAS  Google Scholar 

  28. Corneo B, Moshous D, Gungor T, Wulffraat N, Philippet P, Le Deist FL, et al. Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome. Blood. 2001;97(9):2772–6.

    Article  PubMed  CAS  Google Scholar 

  29. Kung C, Pingel JT, Heikinheimo M, Klemola T, Varkila K, Yoo LI, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nature Medicine. 2000;6(3):343–5.

    Article  PubMed  CAS  Google Scholar 

  30. Moshous D, Callebaut I, de Chasseval R, Corneo B, Cavazzana-Calvo M, Le Deist F, et al. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell. 2001;105(2):177–86.

    Article  PubMed  CAS  Google Scholar 

  31. Buck D, Moshous D, de Chasseval R, Ma Y, le Deist F, Cavazzana-Calvo M, et al. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV. Eur J Immunol. 2006;36(1):224–35.

    Article  PubMed  CAS  Google Scholar 

  32. Fischer A, de Saint Basile G, Le Deist F. CD3 deficiencies. Curr Opin Allergy Clin Immunol. 2005;5(6):491–5.

    Article  PubMed  CAS  Google Scholar 

  33. •• Cossu F. Genetics of SCID. Ital J Pediatr. 2010;36:76. This is an excellent review of the genetics of SCID.

    Article  PubMed  Google Scholar 

  34. Bluestone JA, Mackay CR, O’Shea JJ, Stockinger B. The functional plasticity of T cell subsets. Nat Rev Immunol. 2009;9(11):811–6.

    Article  PubMed  CAS  Google Scholar 

  35. Wan YY. Multi-tasking of helper T cells. Immunology. 2010;130(2):166–71.

    Article  PubMed  CAS  Google Scholar 

  36. Adeli MM, Buckley RH. Why newborn screening for severe combined immunodeficiency is essential: a case report. Pediatrics. 2010;126(2):e465–9.

    Article  PubMed  Google Scholar 

  37. Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973–80.

    Article  PubMed  Google Scholar 

  38. Lindegren ML, Kobrynski L, Rasmussen SA, Moore CA, Grosse SD, Vanderford ML, et al. Applying public health strategies to primary immunodeficiency diseases: a potential approach to genetic disorders. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports/Centers for Disease Control. 2004;53(RR-1):1–29

  39. Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood. 2002;99(3):872–8.

    Article  PubMed  CAS  Google Scholar 

  40. Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. New Engl J Med. 2009;360(5):447–58.

    Article  PubMed  CAS  Google Scholar 

  41. Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. New Engl J Med. 2010;363(4):355–64.

    Article  PubMed  CAS  Google Scholar 

  42. Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–6.

    Article  PubMed  CAS  Google Scholar 

  43. Railey MD, Lokhnygina Y, Buckley RH. Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis. J Pediatr. 2009;155(6):834–40. e1.

    Article  PubMed  Google Scholar 

  44. Patel NC, Hertel PM, Estes MK, de la Morena M, Petru AM, Noroski LM, et al. Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. New Engl J Med. 2010;362(4):314–9.

    Article  PubMed  CAS  Google Scholar 

  45. Bakare N, Menschik D, Tiernan R, Hua W, Martin D. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010;28(40):6609–12.

    Article  PubMed  Google Scholar 

  46. Puck JM. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol. 2007;120(4):760–8.

    Article  PubMed  Google Scholar 

  47. Chan A, Scalchunes C, Boyle M, Puck JM. Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. Clin Immunol. 2011;138(1):3–8.

    Article  PubMed  CAS  Google Scholar 

  48. Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391–8.

    Article  PubMed  Google Scholar 

  49. Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–87.

    Article  PubMed  CAS  Google Scholar 

  50. Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009;302(22):2465–70.

    Article  PubMed  CAS  Google Scholar 

  51. Comeau AM, Hale JE, Pai SY, Bonilla FA, Notarangelo LD, Pasternack MS, et al. Guidelines for implementation of population-based newborn screening for severe combined immunodeficiency. J Inherit Metab Dis. 2010;33 Suppl 2:S273–81.

    Article  PubMed  Google Scholar 

  52. Hale JE, Bonilla FA, Pai SY, Gerstel-Thompson JL, Notarangelo LD, Eaton RB, et al. Identification of an infant with severe combined immunodeficiency by newborn screening. J Allergy Clin Immunol. 2010;126(5):1073–4.

    Article  PubMed  Google Scholar 

  53. Dasouki M OK, Ray A, et al. Deficient T cekk receptor excision circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening. J Clin Immunol 2011; in press.

  54. Azzari C, la Marca G, Resti M. Neonatal screening for severe combined immunodeficiency caused by an adenosine deaminase defect: a reliable and inexpensive method using tandem mass spectrometry. J Allergy Clin Immunol. 2011;127(6):1394–9.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pediatrics, West Virginia University School of Medicine, One Stadium Drive, Morgantown, WV, 26506, USA

    Yesim Yilmaz-Demirdag

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Yilmaz-Demirdag, Y. Should Newborns be Screened for Immunodeficiency? Lessons Learned from Infants with Recurrent Otitis Media. Curr Allergy Asthma Rep 11, 491–498 (2011). https://doi.org/10.1007/s11882-011-0221-8

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