Severe Combined Immunodeficiency
Severe Combined Immunodeficiency: Excerpt from The 5-Minute Pediatric Consult
Timothy Andrews, MD
Severe Combined Immunodeficiency - BASICS
Severe Combined Immunodeficiency - description
Primary immunodeficiency characterized by onset of severe, life-threatening infections in infancy owing to defective or absent T- and/or B-lymphocyte-mediated immunity
Severe Combined Immunodeficiency - epidemiology
- Most patients present by 6 months of age.
- Of severe combined immunodeficiency cases:
- The X-linked form accounts for 50%.
- Adenosine deaminase deficiency accounts for 8%.
- Interleukin-7 receptor deficiency accounts for 10%.
- Janus-associated kinase 3 deficiency accounts for 10%.
Severe Combined Immunodeficiency - incidence
Incidence: Estimated to be 1 in 66,000–100,000 live births
Severe Combined Immunodeficiency - risk factors
Severe Combined Immunodeficiency - genetics
- X-linked and autosomal recessive inheritance
- See Table in Section VI
Severe Combined Immunodeficiency - etiology
- Various defects lead to a similar clinical presentation.
- The X-linked subset is caused by a defect of the common gamma chain of the IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors.
- The autosomal recessive subset is a result of various defects. The most common:
- Adenosine deaminase deficiency
- Purine nucleoside phosphorylase deficiency
- Janus-associated kinase 3 deficiency
- IL-7R deficiency
- RAG-1/AG-2 deficiency
- Defect of Artemis gene
- Absent expression of major histocompatibility complex class I or II molecules
Severe Combined Immunodeficiency - DIAGNOSIS
Severe Combined Immunodeficiency - signs & symptoms
Severe Combined Immunodeficiency - history
- Description of infections, severity, duration, response to treatment
- Family history of unexplained deaths or unusual infections
Severe Combined Immunodeficiency - physical exam
- Evaluation should focus on the presence of infection.
- Often an emaciated-appearing infant
- Marked absence of lymphoid and tonsillar tissue
- Dermatologic evaluation may reveal atypical rashes.
Severe Combined Immunodeficiency - tests
- CBC with differential to assess for degree of lymphopenia; absolute lymphocyte count in the neonatal period normally >2,800/mm3
- T- and B-lymphocyte enumeration:
- T lymphocytes are markedly decreased or absent.
- B lymphocytes are variable but can be normal.
- Mitogen and antigen stimulation tests are markedly decreased or absent.
- Immunoglobulin levels are usually low or absent, although patients can have normal IgG levels in the 1st few months of life owing to transplacentally derived maternal IgG.
- Appropriate cultures to identify pathogens
Severe Combined Immunodeficiency - differencial diagnosis
- Reticular dysgenesis
- Letterer-Siwe syndrome (histiocytosis)
- Omenn syndrome
- HIV infection
- Failure to thrive is the most common presenting problem.
- Recurrent and/or life-threatening infections in infancy with various pathogens (both common and atypical organisms)
- Chronic diarrhea
- Persistent thrush
- Skin rashes are commonly in unusual patterns or locations. They may be the presenting symptom of graft versus host disease.
Severe Combined Immunodeficiency - TREATMENT
Severe Combined Immunodeficiency - general measures
- Bone marrow transplant is the definitive treatment in most cases. Because of the impairment of recipient immune function, conditioning may be less rigorous than in other situations requiring bone marrow transplant.
- Aggressive and early specific antibiotic/antifungal/antiviral therapy for infections
- Pneumocystis carinii prophylaxis
- If required, patients should receive only irradiated blood products. There is a risk of graft versus host disease owing to viable donor leukocytes that may survive in nonirradiated products.
- IV immunoglobulin replacement: This may be required even after bone marrow transplant because of variable B-lymphocyte reconstitution.
- Enzyme replacement therapy has been used in adenosine deaminase-deficient patients.
Severe Combined Immunodeficiency - FOLLOW UP
- Close monitoring of clinical status should be done before bone marrow transplant. This may be every 2–4 weeks, depending on the patient’s status.
- The posttransplant course is variable:
- Overall success rate for matched bone marrow transplant in severe combined immunodeficiency is >65%.
- Success is also being seen in partially matched bone marrow transplant.
- Patients should still be followed closely for signs of infection, graft failure, and graft versus host disease.
Severe Combined Immunodeficiency - complications
- Untreated, most patients succumb to overwhelming infection.
- Graft versus host disease may result from maternal T cells that cross into fetal circulation or from transfusion of nonirradiated blood products.
- Clinical disease can be caused by live vaccines in previous undiagnosed severe combined immunodeficiency patients.
- Increased incidence of malignancy:
- Overall risk of malignancy is ~5%.
- 30-fold increased incidence of lymphoma
Severe Combined Immunodeficiency - bibliography
- Buckley RH. Primary cellular immunodeficiencies. J Allergy Clin Immunol. 2002;109:747–757.
Fischer A, Notarangelo LD. Combined immunodeficiencies. In: Stiehm ER, ed. Immunological Disorders in Infants and Children. 5th ed. Philadelphia: Elsevier Inc.; 2004;447–479.- Gaspar HB, Gilmour KC, Jones AM. Severe combined immunodeficiency—molecular pathogenesis and diagnosis. Arch Dis Child. 2001;84:169–173.
- Gelfand EW, Dosch HM. Diagnosis and classification of severe combined immunodeficiency. Birth Defects. 1983;19:65–72.
- Stephan JL, Vlekova V, Le Deist F. Severe combined immunodeficiency: A retrospective single center study of clinical presentation and outcome in 177 patients. J Pediatr. 1990;123:564–572.
Stites DP, Terr AI. Basic and Clinical Immunolog. 7th ed. Norwalk, CT: Appleton & Lange; 1991:341–344.Winkelstein JA, Blease RM, Winklestein JA, et al., eds. Immune Deficiency Foundation. Patient and Family Handbook for the Primary Immune Deficiency Diseases. 3rd ed. Towson, MD: Immune Deficiency Foundation; 1999–2000.
Severe Combined Immunodeficiency - CODES
Severe Combined Immunodeficiency - icd9
279.2 Combined immunodeficiency
Severe Combined Immunodeficiency - FAQ
- Q: How should children with severe combined immunodeficiency be managed before bone marrow transplant?
- A: Children suspected to have severe combined immunodeficiency should be isolated from potential sources of infection. They should not attend public places such as school because of the risk of obtaining an infection. They should be kept away from ill siblings or relatives, especially if there has been an exposure to chickenpox or other viral illnesses.
- Q: Should patients with severe combined immunodeficiency receive live viral vaccines?
- A: Live viral vaccines are contraindicated in severe combined immunodeficiency. Patients suspected of severe immunodeficiency should not receive live viral vaccines until their immunodeficiency is defined. If the patient is receiving IV immunoglobulin therapy, vaccinations are not required. In addition, siblings of patients with severe combined immunodeficiency who live in the same household should not receive live viral vaccines because of the risk of viral shedding in the siblings.
- Q: What is the chance of another child being affected with severe combined immunodeficiency?
- A: The risk of another child being born with severe combined immunodeficiency in a family with a previously affected child will depend on the type of severe combined immunodeficiency—X-linked: 50% chance of an affected male or carrier female; autosomal recessive causes: 25% chance of an affected child. Genetic counseling should be offered to female carriers of X-linked severe combined immunodeficiency.
- Q: Can severe combined immunodeficiency be diagnosed prenatally?
- A: Prenatal testing is available. Amniocentesis can be performed, and fetal cells can be tested for known genetic cause of severe combined immunodeficiency.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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