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Hypogammaglobulinemia Medication

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

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The standard treatment for hypogammaglobulinemia is IgG replacement, which may be given intravenously or subcutaneously.[9, 10, 20] IgG preparations are approved by the US Food and Drug Administration (FDA) for treatment of primary immunodeficiency disease (primary humoral immunodeficiency) and a few additional indications, but considerable amounts of intravenous immunoglobulins (IVIG) are used "off label" for other conditions.[9, 20]

As reviewed by the American Academy of Allergy, Asthma, and Immunology, the benefit of IgG treatment for these primary immune deficiencies is based on category IIb evidence (13).[9] IVIG is approved for only 2 secondary immune deficiencies: B-cell chronic lymphocytic leukemia (B-CLL) and pediatric HIV. The use of IVIG for primary immune defects with normogammaglobulinemia and impaired specific antibody production is based on category III evidence only.[9]

The usual IVIG dose is 0.4-0.6 g/kg every 3-4 weeks, titrating the dose and interval between infusions to achieve a trough IgG level greater than 500 mg/dL. Usual total monthly doses of subcutaneous IgG (SCIG) are in the same range, given as 100-200 mg/kg/wk. Some practitioners target trough levels 300 mg/dL higher than pretreatment levels, and trough levels >800 mg/dL may improve pulmonary outcomes. Some centers administer a loading dose of 1g/kg if the patient is agammaglobulinemic.[9, 10, 20]

Gammaglobulin may also be given intramuscularly or subcutaneously.[20] The latter format is useful when allergic reactions limit the dose or rate, but it is becoming increasingly popular even when these problems are not present. SCIG can be given at home by parents or by patients themselves, usually requiring several hours of infusion. Intramuscular gammaglobulin injections were the standard of care before IVIG became readily available and are still useful in certain patients because of the simplicity of administration and fewer reactions. However, local injection site pain can be significant, and the doses that can be given this way are limited.

Up to 44% of patients report adverse reactions to IVIG. These most commonly respond to decreasing the rate of the Ig infusion. Usually, the IVIG-associated reactions are infusion-related and include back pain, abdominal aching, nausea, rhinitis, asthma, chills, low-grade fever, myalgias, and headaches. Renal failure is a less common but serious adverse reaction that was predominately caused by sucrose-containing lyophilized IgG preparations that are no longer available in the United States. Infusion rate reduction, systemic steroids, histamine blockers, and antipyretics or nonsteroidal anti-inflammatory drugs (NSAIDs) can help treat or prevent the reactions.

Although the incidence of reactions is highest during the first infusion, they may occur in repeat infusions of the same product. Although anti-IgA antibodies can be associated with increased reactions, most patients (regardless of anti-IgA antibody status) tolerate IVIG that is not depleted of IgA (low-IgA products should be selected for treatment in patients who cannot tolerate IVIG that is not depleted of IgA). Thrombosis, myocardial infarction, hemolytic anemia, hyperviscosity syndrome, and aseptic meningitis are uncommon but reported adverse events.

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Immunoglobulins

Class Summary

Improve clinical and immunologic aspects of the disease.

Immune globulin intravenous (Flebogamma, Gammagard, Gamunex, Privigen) and subcutaneous (Vivaglobin)

 

Results in elevated antiviral or antibacterial antibody titers for 1 mo.

Trough levels >500 mg/dL do not necessarily improve infection control except in certain long-standing infections but may significantly increase cost.

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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.

References
  1. Buckley R. Primary immunodeficiency diseases. 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.

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

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

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

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

  6. Samson M, Audia S, Lakomy D, Bonnotte B, Tavernier C, Ornetti P. Diagnostic strategy for patients with hypogammaglobulinemia in rheumatology. Joint Bone Spine. 2011 May. 78(3):241-5. [Medline].

  7. Artac H, Kara R, Gokturk B, Reisli I. Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy. Clin Exp Med. 2012 Jul 21. [Medline].

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

  9. 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. 2006 Apr. 117(4 Suppl):S525-53. [Medline].

  10. 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].

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

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

  13. Barroeta Seijas AB, Graziani S, Cancrini C, Finocchi A, Ferrari S, Miniero R, et al. The impact of TACI mutations: from hypogammaglobulinemia in infancy to autoimmunity in adulthood. Int J Immunopathol Pharmacol. 2012 Apr-Jun. 25(2):407-14. [Medline].

  14. Buckley R, ed. Immune Deficiency Foundation Diagnostic and Clinical Care Guidelines for Primary Immunodeficiency Diseases, 2nd ed. 2009. Accessed August 17, 2009. Immune Deficiency Foundation. [Full Text].

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

  16. 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. 2009 May. 50(5):764-72. [Medline].

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

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

  19. 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. 2009 Jan 29. 360(5):447-58. [Medline].

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

  21. Ballow M, O'Neil K. Approach to the patient with recurrent infections. 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.

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

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

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

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

  26. Casulo C, Maragulia J, Zelenetz AD. Incidence of Hypogammaglobulinemia in Patients Receiving Rituximab and the Use of Intravenous Immunoglobulin for Recurrent Infections. Clin Lymphoma Myeloma Leuk. 2012 Dec 28. [Medline].

  27. 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. 2000 Apr 28. 288(5466):669-72. [Medline].

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

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

  30. Li James TC. Immunoglobulin structure and function. 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.

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

  32. Priary Immunodeficiency Resource Center. National Primary Immunodeficiency Resource Center. Available at http://info4pi.org. Accessed: October 8, 2007.

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

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

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

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

 
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