eMedicine Specialties > Dermatology > Allergy & Immunology
Bruton Agammaglobulinemia: Treatment & Medication
Updated: Jun 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG.13 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.14
- 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.
- Nutritional supplementation with multivitamins is recommended.
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.
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.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Immunoglobulins
Immunoglobulins are the mainstay of therapy. Passively supply a broad spectrum of IgG antibodies against bacterial, viral, parasitic, and mycoplasmic antigens. Check IgG levels every 3 months and then every 6 months when stable. The goal is to maintain IgG trough levels greater than 500 mg/dL in serum. Check liver function and kidney function 3-4 times a year.
Immune globulin intravenous (Gamimune, Gammar-P, Sandoglobulin, Gammagard)
Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Adjust dose and interval according to individual needs.
Symptomatic adverse effects may be alleviated by premedicating with acetaminophen, diphenhydramine, or methylprednisolone (Solu-Medrol).
Adult
400-600 mg/kg/mo IV over 3-4 h
Pediatric
Administer as in adults
Globulin preparation may interfere with immune response to live virus vaccines (MMR) and reduce efficacy (do not administer within 3 mo of vaccine); live polio virus vaccine should be avoided because of reports of vaccine-related paralytic poliomyelitis
Documented hypersensitivity; IgA deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Check serum IgA before IVIG (use IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Antibiotics
These agents treat common sinopulmonary infections (eg, pneumonia, otitis media). Drugs, such as amoxicillin and amoxicillin/clavulanate, are typical agents used. Fluoroquinolone therapy is useful for respiratory staphylococcal infections and for patients with allergies to other medications. If the infection is caused by Mycoplasma organisms, the drug of choice is clarithromycin. Severe infections may require hospitalization and IV therapy with ceftriaxone or vancomycin.
Amoxicillin (Amoxil, Trimox, Biomox)
Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Adult
250-500 mg PO q8h; not to exceed 3 g/d
Pediatric
20-50 mg/kg/d PO divided q8h; not to exceed 2 g/dose
Reduces efficacy of oral contraceptives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; may enhance likelihood of candidiasis
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult
Uncomplicated infections: 250 mg IM once; not to exceed 4 g
Severe infections: 1-2 g IV qd or divided bid; not to exceed 4 g/d
Pediatric
>7 days: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; caution in breastfeeding
Vancomycin (Vancocin, Lyphocin, Vancoled)
Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot take or in whom no response has occurred with penicillins and cephalosporins or for those who have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.
To avoid toxicity, current recommendation is to assay trough levels after third dose, drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients with renal impairment.
Used in conjunction with gentamicin for prophylaxis in patients allergic to penicillin undergoing GI or GU tract procedures.
Adult
500 mg to 2 g/d IV divided tid/qid for 7-10 d
Pediatric
40 mg/kg/d IV divided tid/qid for 7-10 d
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal failure and neutropenia; red man syndrome is caused by too rapid IV infusion (dose administered over a few min) but rarely happens when dose is administered IV over 2 h or PO or IP; red man syndrome is not an allergic reaction
Clarithromycin (Biaxin)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult
250-500 mg PO q12h for 7-14 d
Pediatric
15 mg/kg PO divided bid
Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI tract adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, and HMG-CoA reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Documented hypersensitivity; coadministration of pimozide
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be a sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapy
Bronchodilators
Bronchodilators are administered via an inhaler to reduce bronchoconstriction and inflammatory response in the lungs. Inhaled beta2-agonists, with or without steroid inhalation therapy, are the standard of care for pulmonary maintenance in XLA.
Albuterol (Proventil, Ventolin)
Beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.
Adult
2-4 mg/dose PO tid/qid; not to exceed 32 mg/d
1-2 puffs via MDI q4-6h; not to exceed 12 inhalations per day
2.5-5 mg via nebulizer q4-6h in 2-5 mL sterile NS or water; to make solution, dilute 0.5 mL (2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS
Pediatric
Oral
2-5 years: 0.1-0.2 mg/kg/dose PO divided tid; not to exceed 12 mg/d
5-12 years: 2 mg/dose PO divided tid or qid; not to exceed 24 mg/d
>12 years: Administer as in adults
MDI
<12 years: 1-2 inhalations qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: 1.25-2.5 mg in 1-2.5 mL q4-6h; to make solution, dilute 0.25-0.5 mL (1.25-2.5 mg) of 0.5% inhalation solution in 1-2.5 mL NS
>5 years: Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Salmeterol (Serevent)
By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, can relieve bronchospasms. Effect may also facilitate expectoration. Adverse effects are more likely to occur when administered at higher or more frequent doses than recommended.
Adult
2 inhalations (42 mcg) bid
Pediatric
<4 years: Not established
4-11 years: 1 inhalation (50 mcg) bid at least 12h apart
>12 years: Administer as in adults
Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered
Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmias associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated to treat acute asthmatic symptoms
Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Beclomethasone (Beclovent, Vanceril)
Inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease number and activity of inflammatory cells, in turn, decreasing airway hyperresponsiveness.
Adult
2 inhalations (84 mcg) tid/qid
Alternatively, 4 inhalations (168 mcg) bid
Severe asthma: 12-16 inhalations (504-672 mcg) per day; adjust dose downward to response; not to exceed 20 inhalations (840 mcg) per day
Pediatric
<6 years: Not established
6-12 years: 1-2 inhalations (42-84 mcg) tid/qid to response
Alternatively, 4 inhalations (168 mcg) bid; not to exceed 10 inhalations (420 mcg) per day
Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant
Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coughing, upper respiratory tract infection, and bronchitis may occur
Fluticasone (Flovent)
Inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease number and activity of inflammatory cells, in turn, decreasing airway hyperresponsiveness.
Adult
2 sprays (50 mcg/spray) per nostril qd; may reduce to 1 spray per nostril for maintenance; not to exceed 4 sprays (200 mcg) per day
Pediatric
1 spray (50 mcg/spray) per nostril qd; may use up to 2 sprays (100 mcg) per nostril; not to exceed 4 sprays (200 mcg) per day
Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant
Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coughing, upper respiratory tract infection, and bronchitis may occur
More on Bruton Agammaglobulinemia |
| Overview: Bruton Agammaglobulinemia |
| Differential Diagnoses & Workup: Bruton Agammaglobulinemia |
 Treatment & Medication: Bruton Agammaglobulinemia |
| Follow-up: Bruton Agammaglobulinemia |
| References |
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Further Reading
Keywords
X-linked agammaglobulinemia, XLA, Bruton agammaglobulinemia, agammaglobulinemia, Bruton disease, Bruton's disease, Bruton tyrosine kinase, Bruton's tyrosine kinase, BTK, BTK gene, BTK gene, immunodeficiency disease
