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Hypogammaglobulinemia Treatment & Management

  • Author: Robert Y Lin, MD; Chief Editor: Michael A Kaliner, MD  more...
 
Updated: Apr 21, 2014
 

Medical Care

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  • 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.[1]
  • 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.[2] 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.[19]
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Contributor Information and Disclosures
Author

Robert Y Lin, MD Professor, Department of Medicine, New York Medical College; Chief, Allergy and Immunology, and Director of Utilization Review, Department Medicine, New York Downtown Hospital

Robert Y Lin, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, New York Allergy & Asthma Society

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, International AIDS Society

Disclosure: Nothing to disclose.

Amit J Shah, MD Allergist/Immunologist, Asthma and Allergy Clinic of Utah, Salt Lake City, UT

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, American College of Physicians

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.

Michael R Simon, MD, MA Clinical Professor Emeritus, Departments of Internal Medicine and Pediatrics, Wayne State University School of Medicine; Professor, Department of Internal Medicine, Oakland University William Beaumont 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, Michigan State Medical Society, Michigan Allergy and Asthma Society, American College of Physicians, American Federation for Medical Research, Royal College of Physicians and Surgeons of Canada, Society for Experimental Biology and Medicine

Disclosure: Received ownership interest from Secretory IgA, Inc. for management position; Received ownership interest from siRNAx, Inc. for management position.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; 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, Association of American Physicians

Disclosure: Nothing to disclose.

Additional Contributors

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, Clinical Immunology Society

Disclosure: Received salary from CSL Behring for employment; Received ownership interest from CSL Behring for employment; Received consulting fee from America''s Health insurance plans for subject matter expert for clinical immunization safety assessment network acvtivity of cdc.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors James O Ballard, MD, Issam Makhoul, MD, and Avi M Deener, MD, to the development and writing of this article.

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