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Combined B-Cell and T-Cell Disorders Follow-up

  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Apr 14, 2015

Further Outpatient Care

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  • Regularly monitor patients for the following parameters:
    • Growth and development
    • Chest radiographs
    • Pulmonary function
    • Immunoglobulin trough levels
      • levels greater than or equal to 400 mg/dL are considered satisfactory. Occasionally, levels greater than 500 mg/dL are required to clear certain viral infections, such as enterovirus meningoencephalitis.
      • Trough levels may need to be titrated in individual patients to determine the level that is needed to prevent recurrent infection.
  • Liver function tests should be performed. If abnormalities are identified, imaging studies of the liver and biliary tree are necessary to exclude malignancies or sclerosing cholangitis (the latter is observed in patients with XHM).

Inpatient & Outpatient Medications

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  • Once initiated, IVIG therapy can be self-administered by the patient.


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  • Specialists in the diagnosis and treatment of these patients should be consulted for their initial evaluation and treatment.


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  • The liberal use of antibiotics helps to decrease the frequency of infections in these patients. Some experts use a rotating regimen of antibiotics on a monthly basis.


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  • Bronchiectasis and cor pulmonale complicate chronic/recurrent lower respiratory tract infections.
  • Hearing loss due to chronic otitis media or meningoencephalitis may affect as many as one third of patients with XLA.
  • The risk of GVHD is high in patients with SCID because of their inability to reject foreign antigens.
  • EBV-associated smooth muscle tumors may occur in patients who are partially reconstituted after bone marrow transplantation for SCID and who may not require surgery or chemotherapy.[22]
  • Central nervous system viral infection is one of the most potentially devastating complications of immunodeficiency, but this is a rare presentation in patients with SCID.
  • Complications related to IVIG therapy include the following:
    • Increased serum viscosity and thromboembolic events, increased risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d postinfusion) can occur.
    • The most common adverse reactions are nonanaphylactic in nature and are characterized by back and abdominal pain, nausea, vomiting, chills, fever, and myalgias. Discontinue the infusion until the symptoms subside; then restart at a slower rate.
    • True anaphylactic reactions are rare and occur seconds to hours after the infusion is started. Typical symptoms consist of flushing, facial swelling, dyspnea, and hypotension. Stop the infusion, and administer epinephrine, steroids, and antihistamines together.
    • The risk of renal tubular necrosis is increased in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease.
    • Transmission of hepatitis C virus (HCV) is much less common now than in the past. Most patients who are HCV RNA–positive contracted their infection in the 1980s when serologic testing of blood donors for this infection was not available. Chronic liver disease in these patients is characterized by a severe clinical course, particularly in those with CVID.
      • Hepatitis B virus (HBV) and hepatitis G virus (HGV) seem to play minor roles in the pathogenesis of chronic liver disease in these patients.
      • A milder form of chronic liver disease with negative serology for HCV, HBV, and HGV infections has been described in these patients. This form occurs, on average, 36 months after the beginning of IVIG therapy, and it is thought to be related to immune phenomena or to a viral infection not yet described.
      • A few non-HCV, non-HBV, and non-HGV patients have a particularly severe course, and granulomatous disease of the liver has been identified in most of them.
      • Lymphoma, especially Burkitt lymphoma, has been reported in patients with ADA deficiency, including those who received prolonged PEG-ADA replacement therapy.


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  • Without treatment, most of the patients with combined B-cell and T-cell disorders die within the first 6 months.
  • Patients who are well nourished, uninfected, and younger than 6 months before transplantation have the best outcomes.
  • Patients with SCID barely survive without stem cell reconstitution. However, gene therapy is an alternative for those cases in which donors are unavailable.
  • Patients with less severe mutations in the ADA gene have survived into adulthood.

Patient Education

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  • Inform patients and their families about the risk of overwhelming infection and the need for immediate intervention.
  • Encourage the use of antibiotics in case symptoms of infection arise, along with immediate referral to the nearest medical facility for evaluation.
Contributor Information and Disclosures

Francisco J Hernandez-Ilizaliturri, MD Associate Professor of Medicine, Department of Medicine, Assistant Professor of Immunology, Department of Immunology, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.


Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences

Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

David Claxton, MD Professor of Medicine, Department of Internal Medicine, Section of Hematology-Oncology, Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Mohammad Muhsin Chisti, MD, FACP Assistant Professor of Hematology and Oncology, Karmanos Cancer Institute, Michigan State University College of Human Medicine

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.


James O Ballard, MD Kienle Chair for Humane Medicine, Professor, Departments of Humanities, Medicine, and Pathology, Division of Hematology/Oncology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

James O Ballard, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American Society of Hematology

Disclosure: Nothing to disclose.

  1. Cavazzana-Calvo M, Fischer A. Gene therapy for severe combined immunodeficiency: are we there yet?. J Clin Invest. 2007 Jun. 117(6):1456-65. [Medline]. [Full Text].

  2. Khiong K, Murakami M, Kitabayashi C, et al. Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model. J Clin Invest. 2007 May. 117(5):1270-81. [Medline]. [Full Text].

  3. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 2000 Apr 28. 288(5466):669-72. [Medline].

  4. Sinha S, Schwartz RA. Severe combined immunodeficiency. Medscape Reference. Updated August 21, 2006. [Full Text].

  5. Bonilla FA, Geha RS. 2. Update on primary immunodeficiency diseases. J Allergy Clin Immunol. 2006 Feb. 117(2 suppl mini-primer):S435-41. [Medline].

  6. Cachafeiro T, Escobar G, Bakos L, Bakos R. Chronic cutaneous cytomegalovirus infection in a patient with severe combined immunodeficiency syndrome. Br J Dermatol. 2013 Sep 6. [Medline].

  7. Bacalhau S, Freitas C, Valente R, Barata D, Neves C, Schäfer K, et al. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency. Case Report Med. 2011. 2011:527569. [Medline]. [Full Text].

  8. Verbsky JW, Baker MW, Grossman WJ, Hintermeyer M, Dasu T, Bonacci B, et al. Newborn Screening for Severe Combined Immunodeficiency; The Wisconsin Experience (2008-2011). J Clin Immunol. 2011 Nov 10. [Medline].

  9. Somech R, Lev A, Simon AJ, Korn D, Garty BZ, Amariglio N, et al. Newborn screening for severe T and B cell immunodeficiency in Israel: a pilot study. Isr Med Assoc J. 2013 Aug. 15(8):404-9. [Medline].

  10. Kelly BT, Tam JS, Verbsky JW, Routes JM. Screening for severe combined immunodeficiency in neonates. Clin Epidemiol. 2013 Sep 16. 5:363-369. [Medline]. [Full Text].

  11. Rozmus J, Junker A, Thibodeau ML, Grenier D, Turvey SE, Yacoub W, et al. Severe Combined Immunodeficiency (SCID) in Canadian Children: A National Surveillance Study. J Clin Immunol. 2013 Oct 12. [Medline].

  12. Levy J, Espanol-Boren T, Thomas C, et al. Clinical spectrum of X-linked hyper-IgM syndrome. J Pediatr. 1997 Jul. 131(1 pt 1):47-54. [Medline].

  13. Zhang C, Zhang ZY, Wu JF, Tang XM, Yang XQ, Jiang LP, et al. Clinical characteristics and mutation analysis of X-linked severe combined immunodeficiency in China. World J Pediatr. 2011 Nov 21. [Medline].

  14. Ridanpaa M, van Eenennaam H, Pelin K, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. 2001 Jan 26. 104(2):195-203. [Medline]. [Full Text].

  15. Chin T, Alonazi N. B-cell and T-cell combined disorders. Medscape Reference. Updated April 5, 2007. [Full Text].

  16. Bertrand Y, Landais P, Friedrich W, et al. Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European Group for Bone Marrow Transplantation and the European Society for Immunodeficiency. J Pediatr. 1999 Jun. 134(6):740-8. [Medline].

  17. Buckley RH, Schiff SE, Schiff RI, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999 Feb 18. 340(7):508-16. [Medline]. [Full Text].

  18. Gennery AR, Flood TJ, Abinun M, Cant AJ. Bone marrow transplantation does not correct the hyper IgE syndrome. Bone Marrow Transplant. 2000 Jun. 25(12):1303-5. [Medline].

  19. Kohn DB. Adenosine deaminase gene therapy protocol revisited. Mol Ther. 2002 Feb. 5(2):96-7. [Medline]. [Full Text].

  20. Casanova JL, Abel L. Primary immunodeficiencies: a field in its infancy. Science. 2007 Aug 3. 317(5838):617-9. [Medline].

  21. Husain M, Grunebaum E, Naqvi A, et al. Burkitt's lymphoma in a patient with adenosine deaminase deficiency-severe combined immunodeficiency treated with polyethylene glycol-adenosine deaminase. J Pediatr. 2007 Jul. 151(1):93-5. [Medline].

  22. Atluri S, Neville K, Davis M, et al. Epstein-Barr-associated leiomyomatosis and T-cell chimerism after haploidentical bone marrow transplantation for severe combined immunodeficiency disease. J Pediatr Hematol Oncol. 2007 Mar. 29(3):166-72. [Medline].

  23. Chapel H, Puel A, von Bernuth H, Picard C, Casanova JL. 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. [Medline]. [Full Text].

  24. Chun HJ, Zheng L, Ahmad M, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002 Sep 26. 419(6905):395-9. [Medline].

  25. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999 Dec. 93(3):190-7. [Medline].

  26. Cooper MD, Lanier LL, Conley ME, Puck JM. Immunodeficiency disorders. Hematology Am Soc Hematol Educ Program. 2003. 314-30. [Medline]. [Full Text].

  27. Creagh EM, Conroy H, Martin SJ. Caspase-activation pathways in apoptosis and immunity. Immunol Rev. 2003 Jun. 193:10-21. [Medline].

  28. Fischer A, Le Deist F, Hacein-Bey-Abina S, et al. Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005 Feb. 203:98-109. [Medline].

  29. Gennery AR, Cant AJ. Diagnosis of severe combined immunodeficiency. J Clin Pathol. 2001 Mar. 54(3):191-5. [Medline]. [Full Text].

  30. Hadzic N, Pagliuca A, Rela M, et al. Correction of the hyper-IgM syndrome after liver and bone marrow transplantation. N Engl J Med. 2000 Feb 3. 342(5):320-4. [Medline]. [Full Text].

  31. Hermanns P, Bertuch AA, Bertin TK, et al. Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia. Hum Mol Genet. 2005 Dec 1. 14(23):3723-40. [Medline]. [Full Text].

  32. Kohn DB. Gene therapy for genetic haematological disorders and immunodeficiencies. J Intern Med. 2001 Apr. 249(4):379-90. [Medline]. [Full Text].

  33. Kuska B. Wiskott-Aldrich syndrome: molecular pieces slide into place. J Natl Cancer Inst. 2000 Jan 5. 92(1):9-11. [Medline]. [Full Text].

  34. Notarangelo LD, Forino C, Mazzolari E. Stem cell transplantation in primary immunodeficiencies. Curr Opin Allergy Clin Immunol. 2006 Dec. 6(6):443-8. [Medline].

  35. Revy P, Malivert L, de Villartay JP. Cernunnos-XLF, a recently identified non-homologous end-joining factor required for the development of the immune system. Curr Opin Allergy Clin Immunol. 2006 Dec. 6(6):416-20. [Medline].

  36. Torgerson TR, Ochs HD. Regulatory T cells in primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol. 2007 Dec. 7(6):515-21. [Medline].

  37. Zhu Q, Watanabe C, Liu T, et al. Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype. Blood. 1997 Oct 1. 90(7):2680-9. [Medline]. [Full Text].

Table 1. Classification of SCID
PathophysiologyCells AffectedInheritanceGenes Involved
Premature cell deathT, B, NKARADA
Defective cytokine–dependent survival signalingT, NKAR

γ c type-XL

JAK3, IL7RA (T cells only), γ c
Defective V(D)J rearrangementT, BARRAG1, RAG2, Artemis
Defective pre-TCR and TCR signalingTARCD3 δ, CD3 ζ, CD3 ε,


AR = autosomal recessive; JAK3 =Janus tyrosine kinase 3; RAG1, RAG2 = recombinase activating gene 1 and 2, respectively; TCR = T-cell receptor; XL = X-linked; V(D)J = variable diversity joining.
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