Hypogammaglobulinemia Treatment & Management

  • Author: Robert Y Lin, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Sep 28, 2010
 

Medical Care

  • IgG replacement therapy is the treatment of choice for most primary immunodeficiency syndromes, including X-linked agammaglobulinemia (Bruton disease; XLA), common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), hyper-IgM, adenosine deaminase (ADA) deficiency, and Wiskott-Aldrich syndrome (WAS). IgG is usually routinely administered intravenously (IVIG) or subcutaneously (SCIG). IgG replacement is usually needed for at least 1 year after hematopoietic stem cell transplantation (HSCT) in patients with SCID.
  • Patients with IgG subclass deficiency should not be given IVIG unless they fail to produce antibodies to protein and polysaccharide antigens and they have significant morbidity due to infection that cannot be managed with antibiotics alone. In selective IgA deficiency, IVIG therapy is not indicated.
  • Effort should be focused on the treatment of infections, allergic reactions, autoimmune diseases, and gastrointestinal diseases. Aggressive and prolonged antibiotic therapy covering S pneumoniae and H influenza is indicated. Because of the high frequency of G lamblia infection in these patients, an empiric course of metronidazole may result in dramatic improvement of the diarrhea and, to a certain extent, of malabsorption syndrome.
  • The treatment of secondary hypogammaglobulinemia is directed at the underlying cause. Successful treatment of nephrotic syndrome and protein-losing enteropathy may result in improvement of Ig levels.
  • IVIG is not indicated for the treatment of lymphoproliferative disorders, unless Ig levels are low in association with recurrent infections or if IVIG is being used for autoimmune conditions such as immune thrombocytopenic purpura (ITP) or immune hemolytic anemia, which may accompany these disorders.
  • Live vaccines (eg, bacille Calmette-Guérin, polio, measles, rubella, mumps) should not be given to patients with T-cell disorders, XLA, or other severe B-cell disorders or to the family members of such patients. In patients with IgA deficiency, live vaccines are not an absolute contraindication if given intramuscularly.
  • High doses of IVIG or intrathecal Ig may be beneficial in patients with XLA who have enteroviral meningoencephalitis.
  • HSCT is the treatment of choice for patients with SCID and, if a matched donor is available, for a patient with ADA deficiency.[3]
  • In patients with ADA deficiency who lack an HLA-identical sibling, enzyme replacement with polyethylene glycol-ADA (PEG-ADA) may be an effective alternative therapeutic agent.
  • Tumor necrosis factor (TNF) inhibitors have been used to treat granulomatous diseases in patients with CVID.
  • Gene therapy has been shown to be successful in reconstituting immune function in infants with X-linked SCID, but efficacy is less proven in older children and young adults.[15] Gene therapy for ADA deficiency is most effective when patients receive myeloablative chemotherapy and are withdrawn from PEG-ADA beforehand. Case series of ADA-deficient patients receiving gene therapy have shown excellent results at 4-year follow-up.[16]
Next

Activity

Special restrictions on physical activity are not needed.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Robert Y Lin, MD  Professor, Department of Medicine, Medical Advisor, Department of Case Management/Utilization Review, New York Medical College; Chief, Allergy and Immunology Section, St Vincent's Catholic Medical Centers, St Vincent's of Manhattan

Robert Y Lin, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American Federation for Medical Research

Disclosure: Nothing to disclose.

Coauthor(s)

Jenny Shliozberg, MD  Associate Clinical Professor, Department of Pediatrics, Division of Allergy and Immunology, Albert Einstein College of Medicine; Consulting Staff, Department of Pediatrics, Montefiore Hospital Medical Center and Albert Einstein College of Medicine; Director of Pediatric Allergy and Immunization Clinic, Children's Hospital at Montefiore Medical Center

Jenny Shliozberg, 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 International AIDS Society

Disclosure: Nothing to disclose.

Amit J Shah, MD  Fellow, Division of Allergy and Immunology, Montefiore Medical Center, Albert Einstein College of Medicine

Amit J Shah, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, and American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Melvin Berger, MD, PhD  Adjunct Professor of Pediatrics and Pathology, Case Western Reserve University; Senior Medical Director, Clinical Research and Development, CSL Behring, LLC

Melvin Berger, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Clinical Investigation, and Clinical Immunology Society

Disclosure: CSL Behring Salary Employment

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Michael R Simon, MD, MA  Clinical Professor Emeritus, Departments of Internal Medicine and Pediatrics, Wayne State University School of Medicine; Adjunct Staff, Division of Allergy and Immunology, Department of Internal Medicine, William Beaumont Hospital

Michael R Simon, MD, MA is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, American Federation for Medical Research, Michigan Allergy and Asthma Society, Michigan State Medical Society, Royal College of Physicians and Surgeons of Canada, and Society for Experimental Biology and Medicine

Disclosure: Secretory IgA, Inc. Ownership interest Management position

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St 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: Alcon Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering/Merck Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting

References

  1. Sneller MC. Common variable immunodeficiency. Am J Med Sci. Jan 2001;321(1):42-8. [Medline].

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

  3. Buckley R. Primary immunodeficiency diseases. In: Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles & Practice. 5th ed. Mo: Mosby: St. Louis; 1998:713-34.

  4. Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr. Oct 2002;141(4):566-71. [Medline].

  5. Ochs HD, Smith CIE, Puck JM. Primary Immunodeficiency Diseases: A Molecular & Cellular Approach. 2nd ed. USA: Oxford University Press; 2006.

  6. Orange JS, Hossny EM, Weiler CR, et al; Primary Immunodeficiency Committee of the AAAAI. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. Apr 2006;117(4 Suppl):S525-53. [Medline].

  7. Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5 Suppl 1):S1-63. [Medline].

  8. Chouksey AK, Berger M. Assessment of protein antibody response in patients with suspected immune deficiency. Ann Allergy Asthma Immunol. Feb 2008;100(2):166-8. [Medline].

  9. Paris K, Sorensen RU. Assessment and clinical interpretation of polysaccharide antibody responses. Ann Allergy Asthma Immunol. Nov 2007;99(5):462-4. [Medline].

  10. Buckley R, ed. Immune Deficiency Foundation Diagnostic and Clinical Care Guidelines for Primary Immunodeficiency Diseases, 2nd ed. 2009. Immune Deficiency Foundation. Available at http://www.primaryimmune.org/publications/book_diag/IDFDiagnosticandClinicalCareGuidelines_2ndEdition.pdf. Accessed August 17, 2009.

  11. Boztug K, Dewey RA, Klein C. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. Oct 2006;8(5):390-5. [Medline].

  12. Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma. May 2009;50(5):764-72. [Medline].

  13. Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med. Oct 15 1997;127(8 Pt 1):613-7. [Medline].

  14. Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. Nov 1999;104(5):1031-6. [Medline].

  15. Sokolic R, Kesserwan C, Candotti F. Recent advances in gene therapy for severe congenital immunodeficiency diseases. Curr Opin Hematol. Jul 2008;15(4):375-80. [Medline].

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

  17. Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am. May 2008;28(2):413-37, x. [Medline].

  18. Ballow M, O'Neil K. Approach to the patient with recurrent infections. In: Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles & Practice. 5th ed. Mo: Mosby: St. Louis; 1998.

  19. Bjoro K, Haaland T, Skaug K. The spectrum of hepatobiliary disease in primary hypogammaglobulinaemia. J Intern Med. May 1999;245(5):517-24. [Medline].

  20. Bonilla FA, Geha RS. Primary immunodeficiency diseases. J Clin Immunol. 2003;111(2 Suppl):S571-81. [Medline].

  21. Bonilla FA, Geha RS. Update of primary immunodeficiency disease. J Clin Immunol. 2006;117(2):S435-41. [Medline].

  22. Carrol WL, Korsmeyer SJ. Immunoglobulins. In: Frank M, Austen K, Claman H, Unanue E, eds. Samter's Immunologic Diseases. 5th ed. Little, Brown and Company: Boston, Mass; 1995:33-51.

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

  24. Cooper N, Davies EG, Thrasher AJ. Repeated courses of rituximab for autoimmune cytopenias may precipitate profound hypogammaglobulinaemia requiring replacement intravenous immunoglobulin. Br J Haematol. Jun 2009;146(1):120-2. [Medline].

  25. Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. Mar 2007;44(Pt 2):131-9. [Medline].

  26. Li James TC. Immunoglobulin structure and function. In: Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles & Practice. 5th ed. Mo: Mosby: St. Louis; 1998:46-57.

  27. Pasternack M. Approach to the adult with recurrent infections. UpToDate. Available at www.uptodate.com. Accessed October 8, 2007.

  28. Priary Immunodeficiency Resource Center. National Primary Immunodeficiency Resource Center. Available at info4pi.org. Accessed October 8, 2007.

  29. Smith JK, Krishnaswamy GH, Dykes R, Reynolds S, Berk SL. Clinical manifestations of IgE hypogammaglobulinemia. Ann Allergy Asthma Immunol. Mar 1997;78(3):313-8. [Medline].

  30. Stiehm ER. Immunologic Disorders in Infants and Children. 4th ed. WB Saunders Co; 1996.

  31. Tsiodras S, Samonis G, Keating MJ, Kontoyiannis DP. Infection and immunity in chronic lymphocytic leukemia. Mayo Clin Proc. Oct 2000;75(10):1039-54. [Medline].

  32. World Health Organization Scientific Group. Primary immunodeficiency diseases. Report of a WHO scientific group. Clin Exp Immunol. Aug 1997;109 Suppl 1:1-28. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.