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Transient Hypogammaglobulinemia of Infancy Treatment & Management

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
Updated: Feb 07, 2014

Medical Care

Transient hypogammaglobulinemia of infancy (THI) treatment is conservative and depends on the severity of infections and the patient's response to therapy. Appropriate antibiotic treatment may be sufficient. However, given emerging evidence that THI is an intrinsic B-cell immunodeficiency, with antibody deficiencies to polysaccharide and conjugated-polysaccharide immunizations (eg, S pneumoniae), treatment with prophylactic antibiotics is reasonable.

Furthermore, in patients with THI who develop severe life-threatening infections or who develop recurrent respiratory tract infections despite antibiotic therapy, a trial of antibody replacement therapy in the form of intravenous immunoglobulin (IVIG) is indicated. Recently, Memmedova et al reported that IVIG treatment in children with THI significantly decreased infections.[24] Furthermore, IVIG therapy did not prolong resolution of THI. Investigators have recommended IVIG for 6-12 months using the usual therapeutic dose of IVIG of 400-800 mg/kg intravenously every 3-4 weeks.[3, 4] Subcutaneous forms of gammaglobulin (Hizentra, Gammagard 10%, Gamunex c) have become available as an alternative to IVIG. The usual therapeutic dose is 100-200 mg/kg subcutaneously per week.

Allergic rhinitis contributes to recurrent otitis media and sinusitis. If allergic rhinitis occurs, the child should be aggressively treated with topical nasal corticosteroids and antihistamines.

Routine immunizations are continued in children with THI. Recently, a conjugated heptavalent pneumococcal vaccine has been recommended for routine immunization in children beginning at age 2 months. Whether this immunization can significantly reduce otitis media in children with THI is unclear. The conjugated heptavalent pneumococcal vaccine covers approximately 85% of the serotype responsible for invasive pneumococcal infection in children.

In studies of healthy children, the pneumococcal vaccine significantly eliminated invasive infections but reduced the frequency of otitis media by only 20%. Sorensen et al have reported that a significant percentage of children with a selective antibody deficiency to bacterial polysaccharide antigens following immunization with the unconjugated vaccine (Pneumovax) develop protective antibody levels following immunization to the conjugated vaccine (Prevnar), with a reduction in infections.[25]


Surgical Care

Many of these children are referred to otolaryngologists for placement of tympanostomy tubes for recurrent otitis media and functional endoscopic sinus surgery (FESS) for chronic sinusitis. Tympanostomy tubes are of uncertain benefit in the prevention of recurrent otitis media, and the potential adverse anatomic and audiologic sequelae of tube placement must be considered. Likewise, some have suggested that FESS is not the cure for chronic sinusitis but that the underlying immunodeficiency disease must be appropriately treated.



These children need to be referred to an allergist, immunologist, or both to evaluate for THI and to ascertain that another immunodeficiency is not present. A definitive diagnosis of THI is a retrospective diagnosis when the immunodeficiency resolves. These patients need to be evaluated over time.

Atopic diseases associated with THI need to be looked for and treated.



No special diet is required unless a food allergy is present.



The child should not attend a daycare center to reduce his or her increased susceptibility to infections. However, physicians need to consider each family's dynamics and economic situation when giving this recommendation.

Contributor Information and Disclosures

Alan P Knutsen, MD Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center

Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

  1. Dorsey MJ, Orange JS. Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy. Ann Allergy Asthma Immunol. 2006 Nov. 97(5):590-5. [Medline].

  2. Siegel RL, Issekutz T, Schwaber J, et al. Deficiency of T helper cells in transient hypogammaglobulinemia of infancy. N Engl J Med. 1981 Nov 26. 305(22):1307-13. [Medline].

  3. Dalal I, Reid B, Nisbet-Brown E, Roifman CM. The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr. 1998 Jul. 133(1):144-6. [Medline].

  4. Cano F, Mayo DR, Ballow M. Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy. J Allergy Clin Immunol. 1990 Feb. 85(2):510-3. [Medline].

  5. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol. 1997 Oct. 100(4):556-62. [Medline].

  6. 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. July 2013. 13(4):257-263. [Medline].

  7. Dalal I, Roifman CM. Hypogammaglobulinemia of infancy. Immunol Allergy Clin North Am. 2001. 21:129-39.

  8. Tiller TL, Buckley RH. Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. J Pediatr. 1978 Mar. 92(3):347-53. [Medline].

  9. Walker AM, Kemp AS, Hill DJ, Shelton MJ. Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities. Arch Dis Child. 1994 Mar. 70(3):183-6. [Medline].

  10. Dressler F, Peter HH, Muller W, Rieger CH. Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition. Acta Paediatr Scand. 1989 Sep. 78(5):767-74. [Medline].

  11. Hayakawa H, Iwata T, Yata J, Kobayashi N. Primary immunodeficiency syndrome in Japan. I. Overview of a nationwide survey on primary immunodeficiency syndrome. J Clin Immunol. 1981 Jan. 1(1):31-9. [Medline].

  12. Wolpert J, Knutsen AP. Natural history of selective antibody deficiency to bacterial polysaccharide antigens in children. Pediatr Asthma, Allergy, Immunol. 1998. 12:183-191.

  13. Whelan MA, Hwan WH, Beausoleil J, et al. Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization. J Clin Immunol. 2006 Jan. 26(1):7-11. [Medline].

  14. Ji-hong Q, Jian-xing Z, Xiao-dong Z, Tong-xin C. Clinical features and follow-up of Chinese patients with symptomatic hypogammaglobulinemia in infancy. Chin Med J. 2009. 122:1877-1883. [Medline].

  15. Moschese V, Graziani L, Avanzini MA, Carsetti R, Marconi M, La Rocca M, et al. A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network. Inter J Immunopath Pharmacol. April-June2008. 21:343-352. [Medline].

  16. Hsueh KC, Chiu HH, Lin HC, et al. Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus sepsis with deep neck infection. J Microbiol Immunol Infect. 2005 Apr. 38(2):141-4. [Medline].

  17. Bukowska-Strakova, Kowalczyk D, Baran J, Siedlar M, Kobylarz K, Zembala M. The B-cell compartment in the peripheral blood of children with different types of primary immunodeficiency. Pediatr Res. 2009. 66:28-34. [Medline].

  18. Moschese V, Carsetti R, Graziani L, Chini L, Soresina AR, La Rocca M, et al. Memory B-cell subsets as a predictive marker outcome in hypogammaglobulinemia during infancy. J Allergy Clin Immunol. August 2007. 120:474-476. [Medline].

  19. Rutkowska M, Lenart M, Bukowska-Strakovà K, Szaflarska A, Pituch-Noworolska A, Kobylarz K, et al. The number of circulating CD4+ CD25high Foxp3+ T lymphocytes is transiently elevated in the early childhood of transient hypogammaglobulinemia of infancy patients. Clin Immunol. April 2011. 140(3):307-310. [Full Text].

  20. Van Winkle RC, Hauck WW, McGeady SJ. Phenotypic parameters predict time to normalization in infants with hypogallaglobulinemia. J Clin Immunol. September 2013. 33:1336-1340. [Medline].

  21. Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. December 2010. 120:214-222. [Medline].

  22. van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. April 2010. 120:1265-1274. [Medline].

  23. Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, et al. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol. March 2012. 129:801-810. [Medline].

  24. Memmedova L, Azarsiz E, Edeer Karaca N, Aksu G, Kutukculer N. Does intravenous immunoglobulin therapy prolong immunodeficiency in transient hypogammaglobulinemia of infancy?. Pediatr Rep. September 2013. 5(3):e14. [Medline].

  25. Sorensen RU, Leiva LE, Giangrosso PA, et al. Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine. Pediatr Infect Dis J. 1998 Aug. 17(8):685-91. [Medline].

  26. Castigli E, Wilson SA, Scott S, et al. TACI and BAFF-R mediate isotype switching in B cells. J Exp Med. 2005 Jan 3. 201(1):35-9. [Medline].

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

  28. Dogu F, Ikinciogullari A, Babacan E. Transient hypogammaglobulinemia of infancy and early childhood: outcome of 30 cases. Turk J Pediatr. 2004 Apr-Jun. 46(2):120-4. [Medline].

  29. Kowalczyk D, Baran J, Webster AD, Zembala M. Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). Clin Exp Immunol. 2002 Mar. 127(3):507-12. [Medline].

  30. Mayer L, Posnett DN, Kunkel HG. Human malignant T cells capable of inducing an immunoglobulin class switch. J Exp Med. 1985 Jan 1. 161(1):134-44. [Medline].

  31. McGeady SJ. Transient hypogammaglobulinemia of infancy: need to reconsider name and definition. J Pediatr. 1987 Jan. 110(1):47-50. [Medline].

  32. Oxelius VA. IgG subclass pattern in primary immunodeficiency disorders. Monogr Allergy. 1986. 19:156-63. [Medline].

  33. Salzer U, Maul-Pavicic A, Cunningham-Rundles C, et al. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol. 2004 Dec. 113(3):234-40. [Medline].

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

  35. Sneller MC, Strober W, Eisenstein E, et al. NIH conference. New insights into common variable immunodeficiency. Ann Intern Med. 1993 May 1. 118(9):720-30. [Medline].

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