Agammaglobulinemia Treatment & Management

Updated: May 06, 2014
  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
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Treatment

Medical Care

Because a patient with agammaglobulinemia is unable to produce specific antibodies, the primary medical treatment is to replace immunoglobulin (Ig). Aggressive treatment with antibiotics for bacterial infections may prevent long-term complications. Live viral vaccines (eg, measles, mumps, rubella [MMR]) are contraindicated in these patients and their families because they may cause vaccine-related infections. On the other hand, dendritic and T-cell responses are normal toward influenza in patients with XLA after administration of inactivated trivalent influenza vaccine.

Intravenous Ig (IVIG) results in improved clinical status with a decrease in serious infections, such as pneumonia, meningitis, and GI infection in numerous studies throughout the world. This also appears to be the case for hypogammaglobulinemia secondary to malignancy.

Patients who received high-dose IVIG (400-500 mg/kg every 3-4 wk) and who maintained IgG levels higher than 500 mg/dL had fewer hospitalizations and infections. Although the goal is to maintain a trough serum IgG level of at least 500 mg/dL, in practice, patients are treated so that they have fewer infections. This may involve higher doses, more frequent infusions, or both. Patients with bronchiectasis need higher doses (eg, 600 mg/kg). Because of the blood-brain barrier, patients with viral meningitis require 1000 mg/kg.

Intravenous access may be difficult to obtain in some patients. Although intramuscular injection of IgG immune serum globulin (ISG) can be performed (0.75 mL/kg), much lower levels result; thus, injections should be given more frequently. Subcutaneous IgG (SCIG) administration is now available with a different preparation. [70] Administration every 14 days of 200 mg/kg body weight resulted in serum IgG levels greater than 7 g/L and was tolerated well in adult patients with X-linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID). [71, 72] Its advantage is that SCIG can be administered in a patient's home without a visiting nurse. The disadvantages are the lack of medical supervision at home and questions of compliance. These considerations need to be addressed on an individual patient basis.

In patients with chronic upper or lower respiratory tract infections and subsequent structural changes, strategic long-term broad-spectrum antibiotics may be needed, in addition to chest physiotherapy and sinus surgery.

An intriguing report from Brazil showed clinical improvement in patients with XLA without IVIG replacement therapy but receiving aggressive respiratory physiotherapy. [14]

Antibiotics are frequently required to manage the infectious complications of antibody deficiencies. Specific antibiotic choices must cover the usual polysaccharide-encapsulated organisms. Higher doses and longer courses are commonly required.

Obtain appropriate cultures to identify causative microorganisms and to establish sensitivities; these results allow for optimal antibiotic therapy. In patients with chronic upper or lower respiratory tract infections and subsequent structural changes, strategic long-term broad-spectrum antibiotics may be needed, in addition to chest physiotherapy and sinus surgery.

Because most infections are sinopulmonary and involve encapsulated bacterial agents, first-line oral antibiotics include amoxicillin, amoxicillin/clavulanate, and cefuroxime axetil. Intravenous ceftriaxone may be required for chronic pulmonary infection, acute severe pneumonia, or sepsis.

As with other patient populations, the risk for penicillin-resistance in S pneumoniae infection is an increasing concern; ceftriaxone, cefotaxime, and vancomycin are used to treat penicillin-resistant organisms.

Less frequent, but significant, infectious agents include Mycoplasma and Ureaplasma species; these organisms are best treated with clarithromycin, which is generally better tolerated than erythromycin in terms of adverse GI effects. Clarithromycin is more effective than azithromycin.

Antibiotic therapy for antibody deficiencies is in the high end of the dose range for immunocompetent individuals, and the duration is the same or longer. Some clinicians advocate rotating the use of antibiotics in select patients with bronchiectasis and frequent exacerbations.

Opportunistic organisms are uncommon in antibody deficiencies, but the risk of infection is increased, particularly in the presence of chronic debilitating pulmonary disease or (more rarely) chronic colitis. Pneumocystis carinii and B cepacia can be etiologic agents in these settings. Trimethoprim-sulfamethoxazole is the first-line drug for both.

Recently released antibiotics such as linezolid for penicillin-resistant pneumococci are presumably effective, although results in primary immunodeficiency diseases are not yet published.

Many infections require interventions in addition to antibiotics. Recurrent or chronic pulmonary infections require annual PFTs. Children older than 5 years should be able to undergo these tests.

Bronchodilators, inhaled corticosteroids, and leukotriene modifiers are integral in the therapy of many patients.

Some patients develop chronic sinusitis despite regular IVIG replacement therapy every 3 weeks. These patients are challenging to treat because antibiotics, N -acetylcysteine, and topical intranasal corticosteroid and saline spray therapies fail to clear pathogens and do not decrease sinus inflammation.

Chronic eczema is treated with moisturizing creams and topical steroids, as in immunocompetent patients. Uncontrolled atopic dermatitis is associated with a greater risk for superinfection than that of topical steroid use.

Nutritional intervention or supplementation and the use of multivitamin and mineral preparations are usually unnecessary in antibody deficiencies, although some patients with autoimmune colitis occasionally require such therapy. Determining the etiology of the diarrhea (often infectious) is more important.

Liver function tests are recommended annually because autoimmune hepatitis and hepatitis C may progress subclinically.

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Surgical Care

Because of the possible development of chronic sinusitis, endoscopic procedures with irrigation may be invaluable in obtaining cultures for microbiological studies. In addition, further surgical intervention may be required to promote sinus drainage.

Patients with chronic sinusitis who may benefit from surgical drainage procedures usually require a consultation with an otolaryngologist, as do children with recurrent otitis media who may improve with the placement of tympanostomy tubes.

Surgical interventions for pulmonary infections include diagnostic and therapeutic thoracentesis, lung biopsy, and care for lung abscesses and bronchopleural fistulas. In addition, obtaining other samples for culture, such as lymph node samples in patients presenting with adenopathy or bronchoalveolar lavage fluid samples in patients with pneumonia who are unable to provide sputum specimen, will allow for a greater selection of appropriate antibiotics for treatment.

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Consultations

Because of the frequent infections and subsequent administrations of antibiotics, treatment requires close partnership with pediatric infectious-disease experts. Autoimmune disorders are treated similarly to diseases in patients with intact humoral immunity; patients may require the expertise of a pediatric rheumatologist. Despite aggressive antibiotic therapy, surgical intervention may be required for chronic sinusitis or for chronic lung disease with abscess, pleural effusion, or other conditions. Concomitant consultation with a pediatric pulmonologist and/or otolaryngologist may be needed. Finally, gastroenterologist may need to be involved because involvement may occur in the GI tract due to 4 processes: infectious, autoimmune, inflammation and malignancy.

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