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Transient Hypogammaglobulinemia of Infancy Clinical Presentation

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

History

Patients with THI may be symptomatic or asymptomatic. Approximately 5% of infants with THI are symptomatic when they are younger than 6 months, 50% become symptomatic at 6-12 months, and 25% become symptomatic when they are older than 12 months.[13] Infants with THI typically begin to experience increasingly frequent and recurrent otitis media, sinusitis, and bronchial infections. Life-threatening infections with polysaccharide-encapsulated bacteria may occur but are unusual. Dalal et al[7] reported that upper respiratory tract infections occurred in most patients and pneumonia occurred in 23% of patients.[3] In a prospective study of 77 children with THI, Moschese et al reported infections in 91%, allergies in 47%, and autoimmune diseases of hemolytic anemia and neutropenia in 4% of patients.[15] Infrequently, severe varicella, persistent oral candidiasis, sepsis, and meningitis were seen.

Because antigen-specific antibody responses are largely intact, this likely accounts for the lack of serious bacterial infections observed in THI. In children older than 3 years, the frequency of infections typically diminishes, even if serum immunoglobulin levels have not yet normalized. T cell immunity is intact, and infections with opportunistic microorganisms do not usually occur.

Although some investigators reported that atopic disease is not frequently associated with THI[7] , other investigators have reported increased incidence of atopic diseases, such as food allergy, asthma, and allergic rhinitis.[9, 12, 1] GI allergic-related symptoms may also occur.

Hematologic abnormalities have also been reported in THI; these included neutropenia and thrombocytopenia.[7] One patient developed acute lymphocytic leukemia (ALL).

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Physical

Physical examination findings are typically normal. Tonsils, adenoids, and lymph nodes are normal in patients with THI, which helps to differentiate THI from other congenital intrinsic B-cell immune defects. In X-linked infantile agammaglobulinemia (Bruton agammaglobulinemia) and common variable immunodeficiency, peripheral lymph nodes, tonsillar tissue, and adenoid tissue are hypotrophic. However, hypertrophic tonsillar tissue and splenomegaly may be present in as many as 25% of patients with common variable immunodeficiency. In hyper-IgM syndrome (HIGM), lymphoid hyperplasia and splenomegaly is uniformly present. Growth is typically normal in patients with THI, as it is in most primary B-cell immunodeficiencies.

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Causes

The cause of THI is unknown. Siegal et al (1981) reported decreased CD4+ T-helper cell function and B-cell synthesis of IgG and IgA in THI; subsequent studies have been able to confirm this.[2] Kowalczyk et al (1997) reported an imbalance of increased TNF and IL-10 synthesis.[16] Antibody responses to protein antigens are normal or near normal; however, a selective antibody deficiency to bacterial polysaccharide antigens (eg, S pneumoniae immunizations, H influenzae type B) is present with IgA deficiency and IgG-2 subclass deficiency. Increased B cells and decreased memory and switched B cells have been observed. Because most children "outgrow" their immunodeficiency, it appears to be a maturational defect in infants and young children. Therefore, THI may represent a maturational defect affecting CD4+ T cells, B cells, and/or antigen-presenting cells.

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Contributor Information and Disclosures
Author

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.

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