Severe Combined Immunodeficiency Treatment & Management

  • Author: Elizabeth A Secord, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: May 5, 2009
 

Medical Care

  • Severe combined immunodeficiency (SCID) is a pediatric emergency and must be worked up and treated promptly. Intravenous immunoglobulin (IVIG) should be administered promptly, and evaluation for bone marrow transplantation (BMT) should be started. Patients with SCID who are treated with BMT before the age of 3.5 months have markedly improved survival rates.
  • Prophylaxis
    • Because T cells are absent and/or dysfunctional, administer Pneumocystis jiroveci pneumonia prophylaxis to all patients until T-cell function is restored by a BMT or other therapy.
    • Trimethoprim-sulfamethoxazole is the drug of choice and can be administered in a patient who is older than 2 months or in whom neonatal jaundice is no longer a concern.
  • X-linked SCID and Janus-associated kinase 3 (JAK3) protein tyrosine kinase (PTK) deficiency
    • A BMT is the primary treatment of choice for most types of SCID when an appropriate donor is found. Pretreatment with ablative chemotherapy is controversial.
    • If B cells do not engraft, the patient may require monthly IVIG replacement therapy.
  • Adenosine deaminase (ADA) deficiency
    • The primary treatment is ongoing polyethylene glycol–conjugated ADA replacement (PEG-ADA) therapy.
    • Gene therapy is in the experimental phase. Although some long-term benefits of gene therapy have been reported for ADA-deficient patients with SCID, serious complications have arisen in some cases of gene therapy in patients with common gamma chain deficiency.
    • The development of leukemia is a complication of gene therapy and appears to be related to the site of insertion of the transgene. Some suggest that better outcomes may occur with different vectors or more specific insertion sites.[20] Greater risk for cognitive abnormalities and emotional and behavioral problems has also been reported in ADA-deficient patients with SCID who received long-term enzyme replacement therapy.[21]
  • Purinenucleotide phosphorylase (PNP) deficiency and bare lymphocyte syndrome: A BMT is the primary therapy when an appropriate donor is available.
  • IL-2 production defects: Intravenous IL-2 replacement is the primary therapy, and a BMT is an alternative if an appropriate donor is available.
  • Omenn syndrome: A BMT is the primary treatment; however, pretreatment ablative chemotherapy is necessary because of maternal cell engraftment.
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Surgical Care

Surgical care is not part of the primary treatment.

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Consultations

  • Immunologist for diagnosis and treatment
  • Hematology/immunology transplant team for an anticipated BMT
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Diet

No diet limitations are necessary.

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Activity

Only infections secondary to the immune deficiency limit activity. The disease itself does not require limitation of physical activity. Keep children with SCID in reverse isolation until BMT or other therapy is initiated.

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Contributor Information and Disclosures
Author

Elizabeth A Secord, MD  Clinical Associate Professor, Department of Pediatrics, Division of Pediatric Immunology, Wayne State University

Elizabeth A Secord, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Eyal Oren, MD  Consulting Staff, Institute for Asthma and Allergy

Eyal Oren, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Charles H Kirkpatrick, MD  Professor of Medicine and Immunology, University of Colorado School of Medicine; Director of Adult Immune Deficiency Program, Department of Medicine, University of Colorado Health Sciences Center; Consulting Staff, Department of Medicine, National Jewish Medical and Research Center

Charles H Kirkpatrick, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Physicians, American Federation for Clinical Research, American Society for Clinical Investigation, and Clinical Immunology Society

Disclosure: Lev Pharmaceuticals Consulting fee Consulting

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Stephen C Dreskin, MD, PhD  Director of Allergy, Asthma, and Immunology Practice, Professor of Medicine, Departments of Internal Medicine and Immunology, University of Colorado Health Sciences Center

Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American Association of Neuropathologists, American Association of Ophthalmic Pathologists, American Association of Oral and Maxillofacial Surgeons, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology

Disclosure: Genentech Consulting fee Consulting

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Abbott Consulting fee Consulting; Alcon Consulting fee Consulting; Glaxo Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering Consulting fee Consulting; Teva Consulting; Meda Honoraria Speaking and teaching

References

  1. Fischer A. Severe combined immunodeficiencies. Immunodefic Rev. 1992;3(2):83-100. [Medline].

  2. Uribe L, Weinberg KI. X-linked SCID and other defects of cytokine pathways. Semin Hematol. Oct 1998;35(4):299-309. [Medline].

  3. Hong R. Disorders of the T cell system. In: Stiehm ER, ed. Immunologic Disorders in Infants and Children. 4th ed. Philadelphia, Pa: WB Saunders; 1996:339-408.

  4. Macchi P, Villa A, Giliani S, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. Sep 7 1995;377(6544):65-8. [Medline].

  5. Candotti F, O'Shea JJ, Villa A. Severe combined immune deficiencies due to defects of the common gamma chain-JAK3 signaling pathway. Springer Semin Immunopathol. 1998;19(4):401-15. [Medline].

  6. Hirschhorn R, Vawter GF, Kirkpatrick JA Jr, Rosen FS. Adenosine deaminase deficiency: frequency and comparative pathology in autosomally recessive severe combined immunodeficiency. Clin Immunol Immunopathol. Sep 1979;14(1):107-20. [Medline].

  7. Reith W, Mach B. The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol. 2001;19:331-73. [Medline].

  8. DeSandro A, Nagarajan UM, Boss JM. The bare lymphocyte syndrome: molecular clues to the transcriptional regulation of major histocompatibility complex class II genes. Am J Hum Genet. Aug 1999;65(2):279-86. [Medline].

  9. Mach B, Steimle V, Reith W. MHC class II-deficient combined immunodeficiency: a disease of gene regulation. Immunol Rev. Apr 1994;138:207-21. [Medline].

  10. Elder ME, Lin D, Clever J, et al. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science. Jun 10 1994;264(5165):1596-9. [Medline].

  11. Villa A, Santagata S, Bozzi F, Imberti L, Notarangelo LD. Omenn syndrome: a disorder of Rag1 and Rag2 genes. J Clin Immunol. Mar 1999;19(2):87-97. [Medline].

  12. O'Driscoll M, Cerosaletti KM, Girard PM, et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell. Dec 2001;8(6):1175-85. [Medline].

  13. Kung C, Pingel JT, Heikinheimo M, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med. Mar 2000;6(3):343-5. [Medline].

  14. Rieux-Laucat F, Hivroz C, Lim A, et al. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. May 4 2006;354(18):1913-21. [Medline].

  15. Dadi HK, Simon AJ, Roifman CM. Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med. Nov 6 2003;349(19):1821-8. [Medline].

  16. Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR. Omenn syndrome due to ARTEMIS mutations. Blood. Jun 1 2005;105(11):4179-86. [Medline].

  17. Hitzig WH, Landolt R, Müller G, Bodmer P. Heterogeneity of phenotypic expression in a family with Swiss-type agammaglobulinemia: observations on the acquisition of agammaglobulinemia. J Pediatr. Jun 1971;78(6):968-80. [Medline].

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

  19. Lebet T, Chiles R, Hsu AP, Mansfield ES, Warrington JA, Puck JM. Mutations causing severe combined immunodeficiency: detection with a custom resequencing microarray. Genet Med. Aug 2008;10(8):575-85. [Medline].

  20. Aiuti A, Cattaneo F, Galimberti S, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. Jan 29 2009;360(5):447-58. [Medline].

  21. Booth C, Hershfield M, Notarangelo L, et al. Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin Immunol. May 2007;123(2):139-47. [Medline].

 
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