Pediatric Bruton Agammaglobulinemia Treatment & Management

  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Sep 28, 2010
 

Medical Care

Until gene therapy becomes developed,[29] the mainstay therapy for Bruton agammaglobulinemia, formally termed X-linked agammaglobulinemia (XLA), and other primary antibody deficiencies is IVIG administration, which has supplanted IMIG injections in most instances.[30] SCIG administration is also possible and offers the advantage of providing IgG levels that are relatively constant compared with the peaks and troughs observed with monthly intravenous therapy.

Numerous studies have shown that IVIG and SCIG given in equal doses provide equal infection prevention in patients with primary antibody deficiency syndromes.[31] A major advantage is that SCIG can be administered at home. However, subcutaneous administration causes frequent local discomfort in various sites in the abdomen, thighs, upper arms, and/or lateral hips. In addition, whether home health care is appropriate for each patient must be evaluated. Not only is compliance an issue, but the lack of close medical observation is also a concern because these patients no longer need to come to the hospital for monthly infusions.

FFP has been used in the past but has the obvious disadvantage of the potential transmission of infectious agents, both known and unknown, despite extensive screening in blood banks.

IVIG doses are usually 400-600 mg/kg/mo or more. The administration interval is usually every 3-4 weeks, based on the average IgG half-life of 21-28 days. The dose and interval are chosen based on the clinical response. Maintaining a trough serum IgG level of approximately 500-800 mg/dL is necessary.

Clinical situations in which higher IVIG doses are given include, but are not limited to, chronic pulmonary infection and chronic enteroviral infection. Therefore, patients with bronchiectasis may need higher doses (eg, 600 mg/kg).

For SCIG administration, 14 days of 200 mg/kg body weight resulted in serum IgG levels of more than 7 g/L and was tolerated well in adult patients with XLA and CVID.[32, 33]

Antibiotics are frequently required to manage the infectious complications of antibody deficiencies. Obtain appropriate cultures to identify causative microorganisms and to establish sensitivities; these results allow for optimal antibiotic therapy.

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 among S pneumoniae 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 XLA, 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.

Sinusitis is typically chronic in older patients and requires therapy with nasal steroids, saline sprays, and surgical intervention in some cases.

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 XLA, 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.

Next

Surgical Care

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.

GI disorders usually do not require surgical intervention and are managed by a gastroenterologist.

Previous
Next

Consultations

A pulmonologist, allergist/immunologist, infectious disease specialist, gastroenterologist, and/or hematologist may be consulted to manage specific complications.

Pulmonologists are particularly valuable in evaluating radiological findings, assisting with bronchodilator therapy, and interpreting detailed PFT results.

Allergy/immunology specialists are trained in the diagnosis and management of primary immunodeficiency disorders and are particularly valuable in diagnosing XLA and guiding IVIG therapy.

Infectious disease specialists are often consulted to determine the infectious etiologies, and they can recommend first-line antibiotics.

Gastroenterologists are essential in the diagnosis and management of inflammatory bowel disease.

Hematologists and clinical immunologists must collaborate to treat autoimmune cytopenias because immunosuppressive therapies for these hematologic disorders further compromise immune function in patients with XLA.

Previous
Next

Diet

Most children and adults with XLA should maintain a normal and nutritious diet.

Patients with inflammatory bowel disease may require a low-fat diet and vitamin supplementation.

Nutritional supplementation with products such as PediaSure, Ensure, or Vivonex is necessary for some patients with persistent malabsorption and malnutrition.

Previous
Next

Activity

Encourage patients with XLA to exercise actively, attend school, and maintain employment. Discourage patients from smoking, exposing themselves to smoke, and using illegal drugs. Instruct them to avoid unnecessary exposure to infectious agents. However, patients may generally benefit from outdoor activities. Considering the relatively good prognosis of XLA, the physician should encourage patients with this immunodeficiency disease to have a positive mental attitude.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Terry W Chin, MD, PhD  Associate Director, Pediatric Allergy/Immunology/Pulmonology, Miller Children's Hospital, Long Beach Memorial Medical Center; Associate Professor, Department of Pediatrics, University of California, Irvine, School of Medicine

Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Thoracic Society, California Thoracic Society, Clinical Immunology Society, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

James M Oleske, MD, MPH  François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, New Jersey Medical School

James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of HIV Medicine, American Academy of Hospice and Palliative Medicine, American Academy of Pain Management, American Academy of Pediatrics, American Association of Pediatrics, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, American Public Health Association, American Society for Microbiology, American Thoracic Society, Arab Board of Family Medicine, Association of Clinical Researchers and Educators (ACRE), Infectious Diseases Society of America, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, National Association of Pediatric Nurse Practitioners, Pediatric Infectious Diseases Society, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

John Wilson Georgitis, MD  Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Ann O'Neill Shigeoka, MD to the development and writing of this article.

References

  1. Bruton OC. Agammaglobulinemia. Pediatrics. Jun 1952;9(6):722-8. [Medline].

  2. Mohamed AJ, Yu L, Backesjo CM, et al. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. Mar 2009;228(1):58-73. [Medline].

  3. Sochorova K, Horvath R, Rozhova D et al. Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia. Blood. 2007;109:2553-6. [Medline].

  4. Doyle SL, Jefferies CA, Feighery C, O'Neill LA. Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. Dec 21 2007;282(51):36953-60. [Medline].

  5. Taneichi H, Kanegane H, Sira MM, et al. Toll-like receptor signaling is impaired in dendritic cells from patients with X-linked agammaglobulinemia. Clin Immunol. Feb 2008;126(2):148-54. [Medline].

  6. Hasan M, Lopez-Herrera G, Blomberg KE. Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice. Immunology. 2008;123:239-49. [Medline].

  7. Schmidt NW, Thieu VT, Mann BA et al. Bruton's tyrosine kinase in required for TLR-induced IL-10 production. J Immunol. 2006;117:7203-10. [Medline].

  8. Winkelstein JA, Marino MC, Lederman HM, et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore). Jul 2006;85(4):193-202. [Medline].

  9. Toth B, Volokha A, Mihas A, et al. Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study. Mol Immunol. Jun 2009;46(10):2140-6. [Medline].

  10. Chun JK, Lee TJ, Song JW, Linton JA, Kim DS. Analysis of clinical presentations of Bruton disease: a review of 20 years of accumulated data from pediatric patients at Severance Hospital. Yonsei Med J. Feb 29 2008;49(1):28-36. [Medline].

  11. De Silva R, Gunawardena S, Wickremesinghe G, Ranasinghe B, Namasivayam Y. Primary immune deficiency among patients with recurrent infections. Ceylon Med J. Sep 2007;52(3):83-6. [Medline].

  12. Aghamohammadi A, Fiorini M, Moin M, et al. Clinical, immunological and molecular characteristics of 37 Iranian patients with X-linked agammaglobulinemia. Int Arch Allergy Immunol. 2006;141(4):408-14. [Medline].

  13. Agarwal S, Mayer L. Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. J Allergy Clin Immunol. Oct 2009;124(4):658-64. [Medline].

  14. Freeman AF, Holland SM. Persistent bacterial infections and primary immune disorders. Curr Opin Microbiol. 2007;10:70-5. [Medline].

  15. Arai A, Kitano A, Sawabe E, et al. Miura ORelapsing Campylobacter coli bacteremia with reactive arthritis in a patient with X-linked agammaglobulinemia. Intern Med. 2007;46:605-9. [Medline].

  16. Mamishi S, Shahmahmoudi S, Tabatabaie H, et al. Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis. Eur J Pediatr. Mar 4 2008;[Medline].

  17. Katamura K, Hattori H, Kunishima T, et al. Non-progressive viral myelitis in X-linked agammaglobulinemia. Brain Dev. Mar 2002;24(2):109-11. [Medline].

  18. Bloom KA, Chung D, Cunningham-Rundles C. Osteoarticular infectious complications in patients with primary immunodeficiencies. Curr Opin Rheumatol. Jul 2008;20(4):480-5. [Medline].

  19. Sikora AG, Lee KC. Otolaryngologic manifestations of immunodeficiency. Otolaryngol Clin North Am. Aug 2003;36(4):647-72. [Medline].

  20. Stewart DM, Tian L, Notarangelo LD, Nelson DL. X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update. Immunol Res. 2007;38(1-3):391-9. [Medline].

  21. Stewart DM, Tian L, Notarangelo LD, Nelson DL. Update on X-linked hypogammaglobulinemia with isolated growth hormone deficiency. Curr Opin Allergy Clin Immunol. Dec 2005;5(6):510-2. [Medline].

  22. Shin DM, Jo EK, Kanegane H, et al. Transcriptional regulatory defects in the first intron of Bruton's tyrosine kinase. Pediatr Int. Dec 2008;50(6):801-5. [Medline].

  23. Lee PP, Chen TX, Jiang LP, et al. Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia. J Clin Immunol. Jan 2010;30(1):121-31. [Medline].

  24. Wang Y, Kanegane H, Wang X, et al. Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. J Clin Immunol. May 2009;29(3):352-6. [Medline].

  25. Teimourian S, Nasseri S, Pouladi N, Yeganeh M, Aghamohammadi A. Genotype-phenotype correlation in Bruton's tyrosine kinase deficiency. J Pediatr Hematol Oncol. Sep 2008;30(9):679-83. [Medline].

  26. Lopez-Granados E, Perez de Diego R, Ferreira Cerdan A, et al. A genotype-phenotype correlation study in a group of 54 patients with X-linked agammaglobulinemia. J Allergy Clin Immunol. Sep 2005;116(3):690-7. [Medline].

  27. Bondioni MP, Duse M, Plebani A, et al. Pulmonary and sinusal changes in 45 patients with primary immunodeficiencies: computed tomography evaluation. J Comput Assist Tomogr. Jul-Aug 2007;31(4):620-8. [Medline].

  28. Gharagozlou M, Ebrahimi FA, Farhoudi A, et al. Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan. Monaldi Arch Chest Dis. Jun 2006;65(2):69-74. [Medline].

  29. Moreau T, Calmels B, Barlogis V, et al. Potential application of gene therapy to X-linked agammaglobulinemia. Curr Gene Ther. Aug 2007;7(4):284-94. [Medline].

  30. Ballow M. Safety of IGIV therapy and infusion-related adverse events. Immunol Res. 2007;38(1-3):122-32. [Medline].

  31. Chinen J, Shearer WT. Subcutaneous immunoglobulins: alternative for the hypogammaglobulinemic patient?. J Allergy Clin Immunol. Oct 2004;114(4):934-5. [Medline].

  32. Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. May 2006;26(3):265-73. [Medline].

  33. Gustafson R, Gardulf A, Hansen S, et al. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies. Clin Exp Immunol. May 2008;152(2):274-9. [Medline].

  34. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. Apr 2006;117(4 Suppl):S525-53. [Medline].

  35. Moore ML, Quinn JM. Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency: advancements into the 21st century. Ann Allergy Asthma Immunol. Aug 2008;101(2):114-21; quiz 122-3, 178. [Medline].

  36. Beaute J, Levy P, Millet V, et al. Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies. Clin Exp Immunol. Dec 16 2009;[Medline].

  37. Howard V, Myers LA, Williams DA, et al. Stem cell transplants for patients with X-linked agammaglobulinemia. Clin Immunol. May 2003;107(2):98-102. [Medline].

  38. Leal RC, Bertelli EC, Soler ZA. Recurrent pneumonia caused by genetic immunodeficiency: a prophylactic and rehabililtative approach. Braz J Infect Dis. 2007;11:307-10. [Medline].

  39. Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5 Suppl A:S225-33. [Medline].

  40. Basile N, Danielian S, Oleastro M, et al. Clinical and molecular analysis of 49 patients with X-linked agammaglobulinemia from a single center in Argentina. J Clin Immunol. Jan 2009;29(1):123-9. [Medline].

  41. Aghamohammadi A, Allahverdi A, Abolhassani H, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia. Respirology. Feb 2010;15(2):289-95. [Medline].

  42. Ziegner UH, Kobayashi RH, Cunningham-Rundles C, et al. Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment. Clin Immunol. Jan 2002;102(1):19-24. [Medline].

  43. Papapetropoulos S, Friedman J, Blackstone C, Kleiner GI, Bowen BC, Singer C. A progressive, fatal dystonia-Parkinsonism syndrome in a patient with primary immunodeficiency receiving chronic IVIG therapy. Mov Disord. Aug 15 2007;22(11):1664-6. [Medline].

  44. Berlucchi M, Soresina A, Redaelli De Zinis LO, et al. Sensorineural hearing loss in primary antibody deficiency disorders. J Pediatr. Aug 2008;153(2):293-6. [Medline].

  45. Aghamohammadi A, Cheraghi T, Rezaei N, et al. Neutropenia associated with X-linked Agammaglobulinemia in an Iranian referral center. Iran J Allergy Asthma Immunol. Mar 2009;8(1):43-7. [Medline].

  46. Jacobs ZD, Guajardo JR, Anderson KM. XLA-associated neutropenia treatment: a case report and review of the literature. J Pediatr Hematol Oncol. Aug 2008;30(8):631-4. [Medline].

  47. Brosens LA, Tytgat KM, Morsink FH, et al. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin Gastroenterol Hepatol. Jan 2008;6(1):115-9. [Medline].

  48. Skull S, Kemp A. Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93. Arch Dis Child. Jun 1996;74(6):527-30. [Medline].

  49. Morwood K, Bourne H, Gold M, et al. Phenotypic variability: clinical presentation between the 6th year and the 60th year in a family with X-linked agammaglobulinemia. J Allergy Clin Immunol. Apr 2004;113(4):783-5. [Medline].

  50. Soresina A, Nacinovich R, Bomba M, et al. The quality of life of children and adolescents with X-linked agammaglobulinemia. J Clin Immunol. Jul 2009;29(4):501-7. [Medline].

  51. Sigmon JR, Kasasbeh E, Krishnaswamy G. X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature. Clin Mol Allergy. Jun 2 2008;6:5. [Medline].

  52. Aghamohammadi A, Moin M, Farhoudi A, et al. Efficacy of intravenous immunoglobulin on the prevention of pneumonia in patients with agammaglobulinemia. FEMS Immunol Med Microbiol. Mar 8 2004;40(2):113-8. [Medline].

  53. Black C, Zavod MB, Gosselin BJ. Haemophilus influenzae lymphadenopathy in a patient with agammaglobulinemia: clinical-histologic-microbiologic correlation and review of the literature. Arch Pathol Lab Med. Jan 2005;129(1):100-3. [Medline].

  54. Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. Feb 2005;203:216-34. [Medline].

  55. Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatrics. 2002;141:566-71. [Medline].

  56. Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med. Jul 13 2000;343(2):108-17. [Medline].

  57. Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. Aug 7 2001;135(3):165-74. [Medline].

  58. Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. Jan 1993;86(1):31-42. [Medline].

  59. Kornfeld SJ, Haire RN, Strong SJ, et al. A novel mutation (Cys145-->Stop) in Bruton's tyrosine kinase is associated with newly diagnosed X-linked agammaglobulinemia in a 51-year-old male. Mol Med. Sep 1996;2(5):619-23. [Medline].

  60. LeBien TW. Fates of human B-cell precursors. Blood. Jul 1 2000;96(1):9-23. [Medline].

  61. Lopez-Herrera G, Berron-Ruiz L, Mogica-Martinez D, Espinosa-Rosales F, Santos-Argumedo L. Characterization of Bruton's tyrosine kinase mutations in Mexican patients with X-linked agammaglobulinemia. Mol Immunol. Feb 2008;45(4):1094-8. [Medline].

  62. Macpherson AJ, Gatto D, Sainsbury E, et al. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. Jun 23 2000;288(5474):2222-6. [Medline].

  63. Minegishi Y, Coustan-Smith E, Rapalus L, et al. Mutations in Igalpha (CD79a) result in a complete block in B-cell development. J Clin Invest. Oct 1999;104(8):1115-21. [Medline].

  64. Morales P, Hernandez D, Vicente R, et al. Lung transplantation in patients with x-linked agammaglobulinemia. Transplant Proc. Aug 2003;35(5):1942-3. [Medline].

  65. Moschese V, Oralndi P, DiMatteo G, et al. Insight into B cell development and differentiation. Acta Paediatr Suppl. 2004;93:48-51. [Medline].

  66. Ochs HD, Smith CI. X-linked agammaglobulinemia. A clinical and molecular analysis. Medicine (Baltimore). Nov 1996;75(6):287-99. [Medline].

  67. Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. Sep 2002;104(3):221-30. [Medline].

  68. Quartier P, Debre M, De Blic J, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. May 1999;134(5):589-96. [Medline].

  69. Revy P, Busslinger M, Tashiro K, et al. A syndrome involving intrauterine growth retardation, microcephaly, cerebellar hypoplasia, B lymphocyte deficiency, and progressive pancytopenia. Pediatrics. Mar 2000;105(3):E39. [Medline].

  70. Smith CIE, Witte ON. X-linked agammaglobulinemia: a disease of Btk tyrosine kinase. In: Ochs HD, ed. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 1999;263-284.

  71. Yu PW, Tabuchi RS, Kato RM, et al. Sustained correction of B-cell development and function in a murine model of X-linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer. Blood. 2004;104:1281-90. [Medline]. [Full Text].

 
Previous
Next
 
This patient presented with recurrent otitis and areas of cellulitis in the diaper area. Pseudomonas aeruginosa and Staphylococcus aureus were isolated from the skin lesions. Autoimmune hemolytic anemia and autoimmune neutropenia were confirmed based on the presence of autoantibodies. The patient has a mutation on exon 15, A504T, which changed an asparagine residue to a valine residue.
Bruton agammaglobulinemia (ie, X-linked agammaglobulinemia [XLA]) in brothers. XLA was diagnosed in the less-robust younger brother when he presented with neutropenia and typhlitis. The older brother, with a history of 7 episodes of pneumonia, was then evaluated and diagnosed with XLA. In both brothers CD19- B cells were less than 1%; this finding is consistent with XLA.
Table 1. Immune Globulin, Intravenous
Brand(Manufacturer)Manufacturing ProcesspHAdditives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].) Parenteral Form and Final ConcentrationsIgA Content mcg/mL
Carimune NF



(ZLB Behring)



Kistler-Nitschmann fractionation, pH 4 incubation, nanofiltration6.4-6.86% solution: 10% sucrose, < 20 mg NaCl/g proteinLyophilized powder 3, 6, 9, 12%Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose free, contains 5% D-sorbitolLiquid 5%< 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25 M glycineReady-for-use liquid 10%37
Gammar-P IV



(ZLB Behring)



Cohn-Oncley fraction II/III, ultrafiltration, pasteurization6.4-7.25% solution: 5% sucrose, 3% albumin, 0.5% NaClLyophilized powder 5%< 20
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Contains no sugar, contains glycineLiquid 10%46
Gammaplex



(Bio Products)



Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation 4.8-5.1Contains sorbitol (40 mg/mL); do not administer if fructose intolerantReady-for-use solution 5%< 10
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III, ultrafiltration, pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized powder 5%< 10
Polygam S/D



Gammagard S/D



(Baxter Bioscience for the American Red Cross)



Cohn-Oncley cold ethanol fractionation followed by ultracentrafiltration and ion exchange chromatography, solvent detergent treated 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophilized powder 5%, 10%< 1.6 (5% solution)
Octagam



(Octapharma USA)



9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events



Cohn-Oncley fraction II/III, ultrafiltration, low pH incubation, S/D treatment pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation, pH 4 incubation, trace pepsin, nanofiltration6.6Per gram of IgG: 1.67 g sucrose,< 20 mg NaClLyophilized powder 3, 6, 9, 12%720
Privigen



(CSL Behring)



pH 4 incubation, octanoic acid fractionation, depth filtration, and virus filtration4.6-510% solution; Preservative-free and sucrose- and maltose-freeReady-to-use solution 10%25
Table 2. Immune Globulin, Subcutaneous
Brand(Manufacturer)Manufacturing ProcesspHAdditivesParenteral Form and Final ConcentrationsIgA Content mcg/mL
Vivaglobin



(ZLB Behring)



Cold ethanol fractionation, pasteurization6.4-7.22.25% glycine, 0.3% NaClLiquid 16% (160 mg/mL)< 50 mcg/mL
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.