Laboratory Studies

Perform initial studies measuring quantitative IgG, IgM, immunoglobulin E (IgE), and immunoglobulin A (IgA) levels. IgG levels should be measured first, preferably after age 6 months, when maternal levels decline. IgG levels below 100 mg/dL are usually indicative of X-linked agammaglobulinemia (XLA). The detection of IgG, IgA, IgM, and IgE levels is related to age. Typically, IgM and IgA are undetectable. All levels are reduced in males with XLA. Age-specific reference range values are available to compare with the patient's level.

Once antibody levels are detected as abnormally low, confirmation is attained by using fluorocytometric analysis of B-lymphocyte and T-lymphocyte markers. CD19⁺ B-cell levels lower than 100 mg/dL are diagnostic of XLA. On fluorocytometric analysis, T-cell values (CD4⁺ and CD8⁺) are usually increased.

Further analysis can be made by detecting IgG responses to T-cell–dependent and T-cell–independent antigens by administering immunizations, such as an unconjugated 23-valent pneumococcal vaccine (T-cell–independent responses) or tetanus, diphtheria, and H influenzae type b immunization (T-cell–dependent responses).

Molecular genetic testing may establish an early confirmed diagnosis of congenital agammaglobulinemia and facilitate carrier detection and prenatal diagnosis.^[30]. From a developing country, blood can be blotted onto the filter paper of Guthrie cards and shipped to a laboratory in the United States for sequencing.^[31]In fact, the use of molecular genetic tests for early diagnosis should be stressed.^[32]

Imaging Studies

Head radiographs may demonstrate an absence of tonsils or adenoids. Further imaging studies of the chest can demonstrate chronic infections or sinopulmonary diseases.

Other Tests

Pulmonary function tests are central to monitoring lung disease, of both the obstructive type and the restrictive type. They should be checked yearly in children who can perform the test (typically age 5 y).

Procedures

Endoscopy and colonoscopy can be used to assess the extent and the progression of inflammatory bowel disease. Bronchoscopy can be useful in diagnosing and tracking chronic lung disease and infections.

Histologic Findings

In patients with X-linked agammaglobulinemia (XLA), lymphoid tissues lack germinal centers, and plasma cells are missing from the lamina propria of the gut and from bone marrow stores. In tissue samples taken to evaluate infection, the most common finding is an intense inflammatory response.

Treatment & Management

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Early stages of B-cell differentiation can be identified by the status of the immunoglobulin genes and by the cell surface markers CD34, CD19, and surface immunoglobulin (sIg). From: Conley ME. Genes required for B cell development. J Clin Invest. 2003;112: 1636-8. Reproduced with permission of American Society for Clinical Investigation via Copyright Clearance Center.

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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)

Franklin Desposito, MD Professor of Pediatrics and Clinical Director, Center for Human and Molecular Genetics, Rutgers New Jersey Medical School; Consulting Staff, Department of Pediatrics, UMDNJ-University Hospital

Franklin Desposito, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Julie R Kenner, MD, PhD Private Practice, SkinHappy MD

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Isabel N. Granja Jander, MD, to the development and writing of this article.