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Hypogammaglobulinemia

Last reviewed: 7 Apr 2025
Last updated: 20 Sep 2022

Summary

Definition

History and exam

Key diagnostic factors

  • recurrent infection
  • infection with Streptococcus pneumoniae or Haemophilus species
  • infection with atypical pathogens
  • repeated antibiotic use
  • respiratory crackles, high-pitched inspiratory squeaks, rhonchi
Full details

Other diagnostic factors

  • absence from school/work
  • failure to thrive
  • diarrhea
  • sinusitis
  • pallor
  • tympanic membrane perforation
  • illness after live vaccines
  • weight loss, night sweats, fevers
  • edema
  • alopecia, goiter, vitiligo
  • eczema
  • small/absent tonsils
  • lymphadenopathy and hepatosplenomegaly
  • history of celiac disease or transfusion reactions
  • muscle fatigability, ptosis, diplopia (if thymoma present)
  • dysmorphic features
  • neurologic involvement
Full details

Risk factors

  • male sex
  • positive family history of primary immunodeficiency
  • severe protein-losing state
  • hematologic malignancy
  • anticonvulsant and immunosuppressive drugs
Full details

Diagnostic tests

1st tests to order

  • CBC
  • serum IgG
  • serum IgA
  • serum IgM
  • serum and urine electrophoresis
  • serum free light chains
  • urine dipstick
  • serum creatinine
  • serum albumin
  • LFTs
  • sputum culture
  • stool culture
  • chest x-ray
Full details

Tests to consider

  • flow cytometry: lymphocyte subsets
  • specific antimicrobial antibodies
  • test immunization response
  • IgG subclasses
  • flow cytometry: protein expression
  • genetic testing
  • enzyme assays
  • abdominal ultrasound
  • CT chest/sinuses
  • CT abdomen
  • pulmonary function test
  • lymph node biopsy
  • small- and large-bowel biopsy
  • polymerase chain reaction (PCR) for viral infection
  • hepatitis B surface antigen, hepatitis B and C PCR
Full details

Treatment algorithm

ACUTE

primary hypogammaglobulinemia

secondary hypogammaglobulinemia

Contributors

Authors

Sara Barmettler, MD

Allergy and Clinical Immunology Unit

Division of Rheumatology, Allergy & Immunology

Massachusetts General Hospital

Boston

MA

Disclosures

SB is an author of some references cited in this topic. SB was on a scientific advisory board for CSL Behring.

Acknowledgements

Dr Sara Barmettler would like to gratefully acknowledge Dr Mohammed Yousuf Karim, Dr Patrick Yong, and Dr Zoe Adhya, previous contributors to this topic.

Disclosures

MYK serves on the advisory board for Allergy Therapeutics. PY and ZA declare that they have no competing interests.

Peer reviewers

John B. Ziegler, MD

Associate Professor of Pediatrics

University of New South Wales

Department of Immunology and Infectious Diseases

Sydney Children's Hospital

Sydney

NSW

Australia

Disclosures

JBZ declares that he has no competing interests.

Charlotte Cunningham-Rundles, MD, PhD

Professor of Medicine and Pediatrics

Immunology Institute

Mount Sinai School of Medicine

New York

NY

Disclosures

CCR is an author of several references cited in this topic.

David Webster, MD, FRCP, FRCPath

Honorary Clinical Scientist

UCL Centre for Primary Immunodeficiency

University College London Medical School

Department of Immunology

Royal Free Hospital

London

UK

Disclosures

DW declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee J Clin Immunol. 2022 Jun 24;1-35 [Epub ahead of print].Full text  Abstract

Otani IM, Lehman HK, Jongco AM, et al. Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: a Work Group report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol. 2022 May;149(5):1525-60.Full text  Abstract

Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205;e1-78.Full text  Abstract

Kohn DB, Hershfield MS, Puck JM, et al. Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol. 2019 Mar;143(3):852-63.Full text  Abstract

National Blood Authority, Australia. Criteria for the clinical use of immunoglobulin in Australia: version 3. 2018 [internet publication].Full text

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
  • Differentials

    • Specific antibody deficiency
    • Hyposplenism
    • Complement deficiency
    More Differentials
  • Guidelines

    • Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: a Work Group report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees
    • Criteria for the clinical use of intravenous immunoglobulin in Australia
    More Guidelines
  • Patient information

    Bronchiectasis

    Pneumonia: do I need a vaccine?

    More Patient information
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