Further Outpatient Care

Careful health care may reduce the number of infections, which are common problems. Chest physiotherapy may be needed to treat such infections.

Further Inpatient Care

Patients should be monitored at regular intervals to be sure potential complications, including acquisition of potential bloodborne infections, have not occurred. In addition, immunologic and pulmonary status of patients with primary immune deficiency diseases should be monitored by the physician. In most cases, doses of IgG are individualized to achieve optimal freedom from acute infection.

Low IgG levels in patients with IgG deficiency are not necessarily associated with deficiencies of antibody responses to immunization with vaccines (eg, tetanus toxoid). Only a small percentage of patients have impaired responses to certain vaccinations. Therefore, measuring antibody levels after vaccination, particularly pneumococcal polysaccharide vaccine (Pneumovax) and Haemophilus vaccine, is crucial before initiating IgG replacement therapy. If the response to vaccination with the above polysaccharide vaccines is inadequate, revaccination with protein-conjugated polysaccharide vaccines, heptavalent pneumococcal conjugate vaccine (Prevnar) and Haemophilus vaccine, is indicated.

Serological tests for specific infections may be unreliable in patients with primary immune deficiency diseases, and false-positive results (ie, positive IgG titers to EBV, hepatitis A virus, and hepatitis B surface antigen) may result from antibodies contained in IgG preparations.^[39]Therefore, physicians may want to use nucleic acid amplification tests (eg, polymerase chain reaction [PCR]) to document the presence or absence of such infections before beginning therapy.

Inpatient & Outpatient Medications

Physicians should stress the importance of good hygiene, good nutrition, and adherence to recommendations for therapy and prevention of infections. The long half-life of IVIG is advantageous, and this type of therapy provides several weeks of protection against related microorganisms. These results have also been observed in patients with IgG subclass deficiency, X-linked agammaglobulinemia, and common variable immunodeficiency (CVID).

Many patients also benefit from the use of prophylactic or chronic treatment regimens of oral antibiotics. Patients with chronic bronchitis or obstructive pulmonary disease may benefit from bronchodilators, topical corticosteroids, or both. Patients with chronic sinus disease may benefit from expert evaluation and management by ENT specialists; this may include surgery.

Complications

Intravenous immunoglobulin (IVIG), whole blood transfusions, and packed red blood cell transfusions are contraindicated in patients who have IgA deficiency. In these patients, the development of anti-IgA antibodies has been associated with both nonhemolytic transfusion reactions and anaphylaxis. If blood transfusions are required in a patient with IgA deficiency, washed red blood cell transfusions should be given.

Prognosis

Patients on appropriate IgG replacement regimens can expect freedom from serious acute bacterial infections. However, patients with CVID are at increased risk of autoimmune disease and malignancy, particularly mucosa-associated lymphoid tissue (MALT) lymphomas.^[7]In addition, freedom from acute infections or exacerbations does not necessarily imply a lack of progression of bronchiectasis or other chronic conditions.

Patient Education

The patient and the patient's family should be taught how to recognize early signs and symptoms of infection so that the patient may obtain treatment as early as possible.

The patient should be advised to avoid crowded places and people who have active infections.

For patient education resources, see the Pneumonia Center, Lung and Airway Center, and Asthma Center, as well as Bacterial Pneumonia, Bronchitis, Asthma, Sinus Infection, and Myeloma.

A common data pool has been established in Europe as an Internet-based database for clinical and research data on patients with primary immunodeficiencies in order to facilitate epidemiological analyses, development of new diagnostic and therapeutic strategies, and the identification of novel disease-associated genes.^[40]

Questions

Melamed IR, Heffron M, McGee S, Ulltate Sanz L, Testori A. A new subset of common variable immune deficiency characterized by reduced C1 esterase inhibitor levels. Ann Allergy Asthma Immunol. 2015 Jul. 115 (1):83-4. [QxMD MEDLINE Link].
Lewandowicz-Uszyńska A, Pasternak G, Pentoś K. Immunoglobulin G Deficiency in Children with Recurrent Respiratory Infections with and Without History of Allergy. Adv Exp Med Biol. 2021. 1289:63-70. [QxMD MEDLINE Link].
Yong PF, Chee R, Grimbacher B. Hypogammaglobulinaemia. Immunol Allergy Clin North Am. 2008 Nov. 28(4):691-713. [QxMD MEDLINE Link].
Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Treatment. 17th ed. Whitehouse Station, NJ: Merck & Co; 2004. Vol 12:
Crassini KR, Zhang E, Balendran S, Freeman JA, Best OG, Forsyth CJ, et al. Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018 Feb 21. [QxMD MEDLINE Link].
Visitsunthorn N, Hengcrawit W, Jirapongsananuruk O, Luangwedchakam V. Immunoglobulin G (IgG) subclass deficiency in Thai children. Asian Pac J Allergy Immunol. 2011 Dec. 29(4):332-7. [QxMD MEDLINE Link].
Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009 Mar 27. [QxMD MEDLINE Link]. [Full Text].
Agarwal S, Cunningham-Rundles C. Assessment and clinical interpretation of reduced IgG values. Ann Allergy Asthma Immunol. 2007 Sep. 99(3):281-3. [QxMD MEDLINE Link].
Paris K, Sorensen RU. Assessment and clinical interpretation of polysaccharide antibody responses. Ann Allergy Asthma Immunol. 2007 Nov. 99(5):462-4. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Barton JC, Bertoli LF, Barton JC, Acton RT. Selective subnormal IgG3 in 121 adult index patients with frequent or severe bacterial respiratory tract infections. Cell Immunol. 2016 Jan. 299:50-7. [QxMD MEDLINE Link].
Aucouturier P, Lacombe C, Bremard C, et al. Serum IgG subclass levels in patients with primary immunodeficiency syndromes or abnormal susceptibility to infections. Clin Immunol Immunopathol. 1989 Apr. 51(1):22-37. [QxMD MEDLINE Link].
Sikora AG, Lee KC. Otolaryngologic Manifestations of Immunodeficiency. Otolaryngologic Clinics of North America. Philadelphia, Pa: WB Saunders; 2003. Vol 36: 647.
Heiner DC, Myers A, Beck CS. Deficiency of IgG4: a disorder associated with frequent infections and bronchiectasis that may be familial. Clin Rev Allergy. 1983 Jun. 1(2):259-66. [QxMD MEDLINE Link].
van Os NJ, Jansen AF, van Deuren M, Haraldsson A, van Driel NT, Etzioni A, et al. Ataxia-telangiectasia: Immunodeficiency and survival. Clin Immunol. 2017 Jan 24. [QxMD MEDLINE Link].
Jain A, Atkinson TP, Lipsky PE, et al. Defects of T-cell effector function and post-thymic maturation in X- linked hyper-IgM syndrome. J Clin Invest. 1999 Apr. 103(8):1151-8. [QxMD MEDLINE Link].
Khvatova AV, Skriabina OA, Kargina IB, et al. [Immunodiagnosis of retinoblastoma]. Vestn Oftalmol. 1992 May-Jun. 108(3):34-6. [QxMD MEDLINE Link].
Caksen H, Oner AF, Arslan S, et al. Immunoglobulin subgroups in children with febrile seizures. Pediatr Int. 2001 Feb. 43(1):58-60. [QxMD MEDLINE Link].
Ojuawo A, Milla PJ, Lindley KJ. Serum immunoglobulin and immunoglobulin G subclasses in children with allergic colitis. West Afr J Med. 1998 Jul-Sep. 17(3):206-9. [QxMD MEDLINE Link].
Ojuawo A, St Louis D, Lindley KJ. Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in its pathogenesis. Arch Dis Child. 1997 Apr. 76(4):345-8. [QxMD MEDLINE Link].
Buckley RH. Immunoglobulin G subclass deficiency: fact or fancy?. Curr Allergy Asthma Rep. 2002 Sep. 2(5):356-60. [QxMD MEDLINE Link].
Stiehm ER. The four most common pediatric immunodeficiencies. J Immunotoxicol. 2008 Apr. 5(2):227-34. [QxMD MEDLINE Link].
Svensson T, Höglund M, Cherif H. Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia. Scand J Infect Dis. 2013 Jul. 45(7):537-42. [QxMD MEDLINE Link].
Freeman JA, Crassini KR, Best OG, Forsyth CJ, Mackinlay NJ, Han P, et al. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013 Jan. 54(1):99-104. [QxMD MEDLINE Link].
Adkinson NF. B Cell Immunodeficiency. Adkinson NF Jr, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FER. Middleton's Allergy: Principles and Practice. 6th ed. St. Louis, Mo: Mosby; 2004. 1062-7.
Ladwig PM, Barnidge DR, Snyder MR, Katzmann JA, Murray DL. Quantification of serum IgG subclasses by use of subclass-specific tryptic peptides and liquid chromatography--tandem mass spectrometry. Clin Chem. 2014 Aug. 60(8):1080-8. [QxMD MEDLINE Link].
Nobre FA, Gonzalez IG, Simão RM, de Moraes Pinto MI, Costa-Carvalho BT. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study. BMC Immunol. 2014 Jun 21. 15:26. [QxMD MEDLINE Link]. [Full Text].
Goyal T, Ali I. Recurrent Herpes Simplex Virus 2 Lymphocytic Meningitis in Patient with IgG Subclass 2 Deficiency. Emerg Infect Dis. 2020 Apr. 26 (4):748-750. [QxMD MEDLINE Link].
Abdou NI, Greenwell CA, Mehta R, Narra M, Hester JD, Halsey JF. Efficacy of Intravenous Gammaglobulin for Immunoglobulin G Subclass and/or Antibody Deficiency in Adults. Int Arch Allergy Immunol. 2009 Feb 12. 149(3):267-274. [QxMD MEDLINE Link].
Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles & Practice of Infectious Diseases. 5th ed. New York, NY: Churchhill Livingston; 2000. Vol 1: 59-61.
Aydıner EK, Kıykım A, Barış S, Özen A, Barlan I. Use of subcutaneous immunoglobulin in primary immune deficiencies. Turk Pediatri Ars. 2016 Mar. 51 (1):8-14. [QxMD MEDLINE Link].
Nicolay U, Kiessling P, Berger M, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006 Jan. 26(1):65-72. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev. 2003 Oct. 17(4):241-51. [QxMD MEDLINE Link].
Torgerson TR. Overview of routes of IgG administration. J Clin Immunol. 2013 Jan. 33 Suppl 2:S87-9. [QxMD MEDLINE Link].
Orange JS, Hossny EM, Weiler CR, et al. 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. [QxMD MEDLINE Link].
Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. 2008 Nov. 28(4):779-802, viii. [QxMD MEDLINE Link].
Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006 May. 26(3):265-73. [QxMD MEDLINE Link].
Ho CH, Chien RN, Cheng PN, Liu JH, Liu CK, Su CS, et al. Aberrant Serum Immunoglobulin G Glycosylation in Chronic Hepatitis B Is Associated With Histological Liver Damage and Reversible by Antiviral Therapy. J Infect Dis. 2014 Jul 10. [QxMD MEDLINE Link].
Gathmann B, Binder N, Ehl S, Kindle G. The European internet-based patient and research database for primary immunodeficiencies: update 2011. Clin Exp Immunol. 2012 Mar. 167(3):479-91. [QxMD MEDLINE Link].
Ekdahl K, Braconier JH, Svanborg C. Impaired antibody response to pneumococcal capsular polysaccharides and phosphorylcholine in adult patients with a history of bacteremic pneumococcal infection. Clin Infect Dis. 1997 Sep. 25(3):654-60. [QxMD MEDLINE Link].
Ferrari S, Giliani S, Insalaco A, et al. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc Natl Acad Sci U S A. 2001 Oct 23. 98(22):12614-9. [QxMD MEDLINE Link].
Gleeson M, McDonald WA, Cripps AW, et al. The effect on immunity of long-term intensive training in elite swimmers. Clin Exp Immunol. 1995 Oct. 102(1):210-6. [QxMD MEDLINE Link].
Guneser S, Antmen B, Altintas D, Yilmaz M. The frequency of IgG subclass deficiency in children with recurrent respiratory infections. Turk J Pediatr. 1996 Apr-Jun. 38(2):161-8. [QxMD MEDLINE Link].
Hamilos DL, Young RM, Peter JB, et al. Hypogammaglobulinemia in asthmatic patients. Ann Allergy. 1992 Jun. 68(6):472-81. [QxMD MEDLINE Link].
Hoffman R. Antibody Deficiencies. Hoffman R, Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000. 765-70.
Imai K, Catalan N, Plebani A, et al. Hyper-IgM syndrome type 4 with a B lymphocyte-intrinsic selective deficiency in Ig class-switch recombination. J Clin Invest. 2003 Jul. 112(1):136-42. [QxMD MEDLINE Link].
Inoue R, Kondo N, Kobayashi Y, et al. IgG2 deficiency associated with defects in production of interferon- gamma; comparison with common variable immunodeficiency. Scand J Immunol. 1995 Feb. 41(2):130-4. [QxMD MEDLINE Link].
Lacombe C, Aucouturier P, Preud'homme JL. Selective IgG1 deficiency. Clin Immunol Immunopathol. 1997 Aug. 84(2):194-201. [QxMD MEDLINE Link].
Lassoued K, Oksenhendler E, Lambin JP, et al. Severe neutropenia associated with IgG2 subclass deficiency and bone marrow T-lymphocyte infiltration. Am J Hematol. 1998 Mar. 57(3):241-4. [QxMD MEDLINE Link].
May A, Zielen S, Reimold I, et al. [Immunoglobulin subclass defects in patients with therapy refractor chronic rhinosinusitis]. HNO. 1999 Jan. 47(1):19-24. [QxMD MEDLINE Link].
Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. 3rd ed. Philadelphia, Pa: WB Saunders; 2000.
Roifman CM, Schroeder H, Berger M, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial. Int Immunopharmacol. 2003 Sep. 3(9):1325-33. [QxMD MEDLINE Link].
Sakiyama Y, Komiyama A, Shiraki K, et al. [Intravenous immunoglobulin (GB-0998) for prophylaxis of recurrent acute otitis media and lower respiratory tract infection in infancy with IgG 2 deficiency]. Nihon Rinsho Meneki Gakkai Kaishi. 1998 Apr. 21(2):70-9. [QxMD MEDLINE Link].
Sandler SG, Trimble J, Mallory DM. Coexistent IgG2 and IgA deficiencies in blood donors. Transfusion. 1996 Mar. 36(3):256-8. [QxMD MEDLINE Link].
Sekerel BE, Saraclar Y, Sanal O, et al. IgG subclasses in children with recurrent respiratory tract infections in an allergy practice. Acta Paediatr Jpn. 1996 Apr. 38(2):124-7. [QxMD MEDLINE Link].
Shackelford PG, Granoff DM, Madassery JV, et al. Clinical and immunologic characteristics of healthy children with subnormal serum concentrations of IgG2. Pediatr Res. 1990 Jan. 27(1):16-21. [QxMD MEDLINE Link].
Shephard RJ, Rhind S, Shek PN. The impact of exercise on the immune system: NK cells, interleukins 1 and 2, and related responses. Exerc Sport Sci Rev. 1995. 23:215-41. [QxMD MEDLINE Link].
Smith LJ, Szymanski W, Foulston C, et al. Familial enteropathy with villous edema and immunoglobulin G2 subclass deficiency. J Pediatr. 1994 Oct. 125(4):541-8. [QxMD MEDLINE Link].
Snowden JA, Milford-Ward A, Reilly JT. Symptomatic IgG3 deficiency successfully treated with intravenous immunoglobulin therapy. Postgrad Med J. 1994 Dec. 70(830):924-6. [QxMD MEDLINE Link].
Tezcan I, Ersoy F, Sanal O, et al. IgG subclass deficiency in children with recurrent infections. Turk J Pediatr. 1991 Jul-Sep. 33(3):163-6. [QxMD MEDLINE Link].
Travin M, Macris NT, Block JM, Schwimmer D. Reversible common variable immunodeficiency syndrome induced by phenytoin. Arch Intern Med. 1989 Jun. 149(6):1421-2. [QxMD MEDLINE Link].
Tsujihata M, Satoh A, Yoshimura T, et al. Effect of myasthenic immunoglobulin G on motor end-plate morphology. J Neurol. 2003 Jan. 250:75-82. [QxMD MEDLINE Link].
Van Kessel DA, Horikx PE, Van Houte AJ, et al. Clinical and immunological evaluation of patients with mild IgG1 deficiency. Clin Exp Immunol. 1999 Oct. 118(1):102-7. [QxMD MEDLINE Link].

Media Gallery

Immunoglobulin G deficiency. Schematic representation of an immunoglobulin G molecule. CH indicates constant region of heavy chain; CL, constant region of light chain; VH, variable region of heavy chain; and VL, variable region of light chain.
Immunoglobulin G deficiency. Human immunoglobulin G subclasses.
Immunoglobulin G deficiency. Changes in serum immunoglobulin G concentrations during infancy and childhood.
Immunoglobulin G deficiency. Schematic representation of the molecular interaction of CD40 on B cells, with CD40L on T cells involved in the switch from immunoglobulin M to immunoglobulin G.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Janet Vafaie, MD Private Practice

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, 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, Society for Experimental Biology and Medicine

Disclosure: Have a 5% or greater equity interest in: Secretory IgA, Inc. ; siRNAx, Inc.<br/>Received income in an amount equal to or greater than $250 from: siRNAx, Inc.

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.