Bruton Agammaglobulinemia Clinical Presentation

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Mar 9, 2012
 

History

Recurrent infections begin in infancy and persist throughout adulthood.

The most common presentation of X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is increased susceptibility to encapsulated pyogenic bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas species. Skin infections in patients with XLA are mostly caused by group A streptococci and Staphylococcus aureus, and they can present as impetigo, cellulitis, abscesses, or furuncles.

A form of eczema that resembles atopic dermatitis may be evident, along with an increased incidence of pyoderma gangrenosum, vitiligo, alopecia totalis, and Stevens-Johnson syndrome (from increased use of medications). Other infections that commonly present with XLA include enteroviral infections, sepsis, meningitis, and bacterial diarrhea (often caused by common organisms, such as Campylobacter jejuni and Giardia species). Individuals who are affected may have an increased incidence of autoimmune diseases leading to thrombocytopenia, neutropenia, hemolytic anemia, and rheumatoid arthritis.[9] Persistent enteroviral infections may rarely lead to fatal encephalitis or a dermatomyositis-meningoencephalitis syndrome.[10] In addition to the neurologic changes, clinical manifestations of this syndrome include edema, muscle wasting, and an erythematous rash over the extensor surfaces of the joints.

Males affected with XLA usually present when they are younger than 1 year with unusually severe and/or recurrent otitis media, sinopulmonary infections, and pneumonia. The most common pathogen is S pneumoniae, followed by H influenzae type b, staphylococcal species, Neisseria meningitidis, and Moraxella catarrhalis. Clinical suspicion of XLA should be followed up with a detailed family history. One third to one half of all patients with XLA have spontaneous mutations and no family history of immunodeficiency. Suspect disease when increased otitis media, sinusitis, chronic coughs, and pneumonias.

For children younger than 12 years, typical infections are caused by encapsulated bacteria. Common infections in this age group are recurrent pneumonia, sinusitis, and otitis media caused by S pneumoniae and H influenzae type b that are difficult to treat.

In adulthood, skin manifestations become more common, usually due to Staphylococcus and group A Streptococcus organisms. Otitis media is replaced by chronic sinusitis, and pulmonary disease becomes a constant recurring problem, in both the restrictive form and the obstructive form.

Both infants and adults can have autoimmune diseases associated with XLA. Typically, these disorders include arthritis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and inflammatory bowel disease. Inflammatory bowel disease can be very difficult to control and often promotes chronic weight loss and malnutrition.

Diarrhea is common and is caused by Giardia or Campylobacter species.

Patients with XLA are prone to enteroviral infections, including poliovirus.

Ureaplasma and Mycoplasma infections may be more common than in the general population, as are bladder and joint infections.

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Physical

Male infants with X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, may appear physically smaller than male infants without XLA because of delayed growth and development from recurrent infections. Rarely, XLA is associated with growth hormone deficiency, leading to significantly shorter stature in males with XLA than in males without XLA of the same age.

On examination, the lymph nodes, the tonsils, and other lymphoid tissues may be very small or absent.

The disease is diagnosed when the male infant repeatedly becomes ill with various sinopulmonary infections, otitis media, or staphylococcal skin infections and conjunctivitis that do not respond well to antibiotic therapy. These severe infections may be associated with neutropenia.

Diarrhea due to Giardia, C jejuni, Shigella, and Salmonella infections may be a clinical feature of XLA.

Pyoderma gangrenosum – like ulcers and cellulitis of the lower extremities may be seen with X-linked (Bruton) agammaglobulinemia.[11] They may occur with recurrent fever and be caused by Helicobacter bilis, an organism difficult recover in blood and wound cultures that can be identified using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry.

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Causes

The BTK mutations underlying X-linked agammaglobulinemia (XLA) interferes with the development and the function of B lymphocytes and their progeny. The major block occurs in the development of pro–B cells to pre–B cells and then to mature lymphocytes. Patients can have pre–B cells in the marrow, but they have few, if any, functional (mature) B cells in the peripheral blood and the lymphoid tissues.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Franklin Desposito, MD  Professor of Pediatrics and Clinical Director, Center for Human and Molecular Genetics, UMDNJ-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, American Medical Association, American Society of Human Genetics, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Julie R Kenner, MD, PhD  Consultant, Clinical Research, Medical Affairs, VaxGen, Inc; Private Practice, Kenner Dermatology Center

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology and American Society of Tropical Medicine and Hygiene

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD  Herman Beerman Associate 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 and American Society of Dermatopathology

Disclosure: Lippincott Williams Wilkins Royalty Textbook editor; DLA Piper Consulting fee Consulting

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

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

Disclosure: Nothing to disclose.

Additional Contributors

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.

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