Medical Care
No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. [29] Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. [30]
Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. When possible, cultures must be obtained to elucidate sensitivities; many organisms will show resistance in this population. Infections with Streptococcus pneumococcus, in particular, may require ceftriaxone, cefotaxime, or vancomycin for eradication.
Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.
Chronic dermatologic manifestations of atopic dermatitis and eczema are controlled with daily moisturizing lotions and topical steroids.
Infliximab has been used with X-linked agammaglobulinemia in a patient with associated granulomatous small bowel enteropathy. [31]
Nutritional supplementation with multivitamins is recommended.
The feasibility of using gene-corrected hematopoietic stem cells to complement the immune defects in mouse models has been studied. It may be propitious to initiate stem cell–based therapy for XLA using gene-corrected autologous hematopoietic stem cells. [32] Recent efforts suggest restoring Bruton tyrosine kinase may be practical as a future therapeutic option. [33]
Further inpatient care
Patients with X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, are hospitalized for severe infections or acute decompensation.
Immunologists are well equipped to treat the clinical illnesses of XLA. If a patient chooses to have health care provided by a primary care physician, the physician should have a special interest and experience in immunodeficiency diseases.
Surgical Care
Surgical intervention for X-linked agammaglobulinemia (XLA) is limited to severe acute infections or unresponsive chronic infections. The most common procedures involve treating patients with recurrent otitis by inserting tympanostomy tubes and treating patients with chronic sinusitis by surgical drainage.
Special concerns for patients with XLA arise preceding surgery. In this situation, intravenous immunoglobulin (IVIG) is preoperatively administered to prevent infection. Live vaccines must be withheld.
Consultations
Consult specialists in genetics, dermatology, gastroenterology, pulmonology, infectious diseases, and hematology.
Diet
Patients with XLA should follow their normal diet supplemented by a multivitamin. No dietary limitations are specific for XLA, although a low-fat diet may be needed for patients with inflammatory bowel disease.
Activity
Patients with XLA have no specific physical limitations. Not smoking or not being exposed to smoke is strongly recommended for patients because of the increased risk of sinopulmonary infection.
Prevention
Families with a known mutated gene can be prenatally evaluated to better prepare for the infant's care. Testing is performed via amniocentesis or chorionic villi sampling. After birth, testing is performed on cord blood.
A BTK gene mutation screening study may be performed in families with the BTK gene defect to detect new cases. In one study from Taiwan, 52 members of 4 unrelated families with the BTK gene defect for BTK gene mutation detected 6 symptomatic living affected individuals and 11 asymptomatic female carriers. [34]
Long-Term Monitoring
Patients with XLA are treated well medically as outpatients. Treatments with IVIG and necessary antibiotics for infections are all provided on an outpatient basis. Most tests and evaluations can be performed and most medications can be administered on an outpatient basis.
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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.
