Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pediatric Bruton Agammaglobulinemia Follow-up

  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: May 07, 2014
 

Further Outpatient Care

New infections can usually be medically managed on an outpatient basis, and appropriate cultures, if indicated, can usually be obtained in the clinical setting. Extensive diagnostic tests including CSF analyses with polymerase chain reaction (PCR) for viral genomes, neuroimaging, and electrophysiologic studies need to be pursued to evaluate for infectious or autoimmune complications.

If indicated, blood samples should be obtained to detect viral RNA or DNA, and liver function tests should be performed to evaluate and to monitor hepatitis. Other infections require follow-up on an outpatient basis.

Frequent monitoring of the patient's pulmonary status is important because the main long-term complication continues to be chronic lung disease. Pulmonary lung function should be assessed regularly, and high-resolution CT scans of the lungs should be performed since bronchiectasis can develop (even in patients on chronic IVIG therapy). If end-stage lung disease develops, lung transplantation has been performed in patients with agammaglobulinemia using intensive IVIG administration (every 48 h during the first 10 d after transplant).

The medical provider is responsible for withholding live viral vaccines. The administration of the live-attenuated oral poliovirus vaccine can cause progressive and fatal meningoencephalitis, as can wild-type enteroviruses. Other live-attenuated vaccines are also contraindicated, although they have not caused such devastating infection.

Avoid live viral vaccines for patients with agammaglobulinemia and any siblings or other children in the household because the attenuated virus is excreted and poses a threat to immunodeficient patients. If the patient has been exposed to a live viral vaccine, or if the live poliovirus has been given, obtain a stool culture to determine if the patient has the attenuated virus. Although most laboratories can determine the presence of an enterovirus, poliovirus identification requires sending the viral specimen to a state referral laboratory. Administer intravenous immunoglobulin (IVIG) and maintain serum immunoglobulin (Ig)G levels higher than 500 mg/dL.

Next

Further Inpatient Care

Hospitalization has become unusual for patients with Bruton agammaglobulinemia, formally termed X-linked agammaglobulinemia (XLA), because home health organizations can provide intravenous antibiotics, pulmonary care, and nutritional interventions on an outpatient basis. Ig replacement therapy with either IVIG administered in outpatient clinics or SCIG at home to minimize interruptions of daily living is the mainstay of medical treatment.

The rationale for hospitalizing patients with XLA who are receiving IVIG replacement is usually to provide an adequate workup of a puzzling infection, to manage severe gastrointestinal issues, to address acute pulmonary decompensation in the presence of chronic pulmonary disease, or to assess and treat severe autoimmune disorders.

Compared with others, patients who are treated have fewer acute overwhelming infections that require hospitalization.

Successful cure has been reported using stem cells from either cord blood or bone marrow from histocompatibility leukocyte antigen (HLA)–matched siblings.[55]

Previous
Next

Inpatient & Outpatient Medications

Administer IVIG to every patient with agammaglobulinemia. In rare circumstances (eg, temporary lack of venous access), IMIG can be given. Subcutaneous administration of IVIG is an option depending on individual preferences. A survey revealed that 90% of 1243 (1119) patients with primary immunodeficiencies in 16 countries receive IVIG in an inpatient setting, whereas 7% (87) are treated with subcutaneous Ig (SCIG), mainly at home.[56] However, this survey was performed before the SCIG preparation was available in the US.

Because these patients risk developing unusual infections, attempt to identify any pathogens in either the respiratory or gastrointestinal tracts. More modern techniques using polymerase chain reaction (PCR) helped diagnose Mycoplasma pneumoniae osteomyelitis in a patient with hypogammaglobulinemia with repeatedly sterile pus cultures.

For patients to have refractory Campylobacter jejuni infection longer than 2 years is not unusual, despite therapy with various antibiotics and IVIG preparations.

In patients with respiratory symptoms, analyzing bronchial samples obtained during bronchoscopy using traditional culture as well as PCR may help determine the various viruses and bacteria present.

See Medical Care and Medication.

Previous
Next

Transfer

Most clinical immunologists believe that they should usually manage clinical illnesses related to XLA and other primary immunodeficiency diseases because these illnesses are rare and their complications are rarer still.

Generally, primary care physicians who treat patients with XLA and other primary immunodeficiency diseases must have a special interest in immunology and adequate experience in managing these complex problems.

Previous
Next

Deterrence/Prevention

Prenatal diagnosis in families known to carry a mutated gene may allow better preparation for the infant's care by the family and the physician.

In families in which a male is diagnosed with XLA, females may wish to undergo evaluation to determine if they are carriers; if they are, genetic counseling regarding future pregnancies can be very beneficial.

Certainly, assessment of B and T cells with flow cytometry is important for an infant at risk before infections develop.

Gene therapy is not yet available for XLA. However, encouraging results using retroviral-mediated gene transfer have been recently reported in a murine model of XLA.

Because patients continue to have improved outcomes, stem cell transplantation is not considered appropriate because of its risk and need for aggressive immunosuppression.

Previous
Next

Complications

Major complications are caused by frequent or recurrent infections that result in chronic pulmonary disease and/or chronic enteroviral infection of the CNS.

All of the complications (such as pneumonia, otitis media, and diarrhea) before immunoglobulin replacement therapy was started were reduced, except sinusitis and conjunctivitis. Although most children with XLA develop recurrent bacterial respiratory tract infections during infancy, 20% are diagnosed in children aged 3-5 years, reflecting the widespread use of antibiotics. Unfortunately, permanent damage to the lungs with bronchiectasis may have already occurred.[57] This could be reflected in continued decline in pulmonary function testing.[58] However, increasing the dose may blunt this decline.

The presence of bronchiectasis has also been found to correlate with continued risk for developing pneumonia despite immunoglobulin replacement therapy.[59] A recent report indicates that the development of chronic lung disease was significantly related to age at diagnosis and inappropriate treatment.[60] However, even with immunoglobulin replacement therapy, 38.4% of XLA patients continued to experienced pneumonia and respiratory problems.[61, 62]

Recurrent infections may eventually cause either obstructive disease or combined obstructive and restrictive lung disease. IVIG treatment, aerosol treatments with bronchodilators, and chest physiotherapy, such as postural drainage, may prevent further damage in these patients. No good studies have examined the effectiveness of aerosol treatments in these patients, although one may speculate that mobilization of secretions should help. Similarly, no good studies have examined the usefulness of prophylactic antibiotics, either systemically or topically (ie, aerosolized).

Chronic sinusitis may also result from repeated infections and subsequent structural changes. Chronic ear infections may result in hearing loss.

Autoimmune diseases (eg, inflammatory bowel disease, atrophic gastritis, pernicious anemia) are also observed in patients. Other noninfectious complications that are particularly prevalent include autoimmune disorders such as arthritis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, and autoimmune neutropenia. One center reported that 26.7% of XLA patients have developed neutropenia.[63] There have been attempts to treat with granulocyte colony-stimulating factor (filgrastim).[64] Treatment may also consist of increasing the dose of immunoglobulin replacement and/or steroids or rituximab.[65] A dermatomyositis syndrome has been frequently reported in boys whose past treatments did not include IgG at the high doses currently administered. See section on History.

Reports that showed progressive neurodegeneration in patients with primary immunodeficiency on IVIG treatment are concerning.[66, 67] Extensive diagnostic tests including CSF analyses with PCR for viral genomes, neuroimaging, and electrophysiologic studies need to be pursued to evaluate for infectious or autoimmune complications.

Sensorineural hearing loss may be increased in patients with antibody deficiency (both XLA and CVID) and suggest regular audiologic evaluation.[68]

Eczema and asthma are more frequent in these patients than in immunocompetent individuals.

Patients with low or absent immunoglobulin levels have increased risk of malignancy, especially in the lymphoreticular and GI organs, which may be the result of altered immune surveillance. However, the risk for XLA appears to be much less than the other immunodeficiency syndromes. There has been a report on multiple neoplasms in the GI tract[33] and gastric adenocarcinomas.[69]

Attempts to correlate clinical outcome with severity of various mutations have not been successful.[70] Early diagnosis and treatment continue to result in the best outcome.

Previous
Next

Prognosis

IVIG treatment has increased the survival rates of patients with XLA. Interestingly, patients with XLA who receive early and adequate IgG replacement seem to do better than patients with other causes of hypogammaglobulinemia and CVID. Comparisons of XLA and CVID have shown that patients with XLA incur less severe chronic pulmonary disease, less devastating hepatitis C infection (acquired through intravenous immunoglobulin and other blood products), and little risk for malignancy.

The development of chronic lung disease is significantly related to age at diagnosis and inappropriate treatment.[60] However, even with immunoglobulin replacement therapy, 38.4% of patients may continue to experienced pneumonia.[62] Although patients continue to die from chronic pulmonary disease, some now survive into the fifth and sixth decades of life. The development of bronchiectasis despite immunoglobulin replacement therapy in XLA has been well documented.[59, 71]

Patients who begin IVIG replacement therapy when they are younger than 5 years have had prolonged survival and decreased morbidity and mortality rates.

Men with XLA have survived into the fifth decade of life despite suboptimal immunoglobulin replacement because IVIG did not become available until the mid 1980s. The oldest reported patients with XLA are in the sixth decade of life.[72]

Other causes of mortality include complications of colitis and liver disease.

Predominant serious viral infections are enteroviral and may involve the attenuated vaccine strains of poliovirus. Chronic enteroviral CNS infection is the major factor in severe outcomes. Patients with XLA adequately manage other viruses such as measles and varicella. Herpes simplex infections are more likely to be recurrent, and the common wart can be difficult to control.

A theoretical concern is that the frequency of malignancies may increase as the population of patients with XLA ages because the incidence of malignancies increases in older patients with other primary immunodeficiencies. Examples include X-linked hyper-IgM disease, CVID, and Wiskott-Aldrich syndrome, all of which involve antibody deficiencies. However, whether the risk of malignancy is due to the deficiency of antibody or due to other immune dysregulation that accompanies these disorders is not clearly known. Case reports of certain neoplasms, such as colorectal neoplasms,[33] suggest the need for colorectal screening in patients with XLA. GI adenocarcinomas are not unusual.[69]

Despite these health concerns, measurement of quality of life indicates that these patients perceive a higher quality than those with rheumatological disorders, although both groups were lower than healthy controls.[73]

Previous
Next

Patient Education

Patients and families must understand the need to recognize and treat infections early.

Recognition of the disease can be difficult because of the subtle presentation of infections caused by the poor inflammatory response compared with that of an immunocompetent host. IVIG replacement may also lull patients into delaying medical care because of both their emotional reliance on IVIG and because of the slowly progressive manifestation of infection, compared with the acute overwhelming presentation in an individual with XLA who does not receive treatment.

Physicians can overcome the tedious nature of chronic pulmonary care and the difficulty in using inhalers by repeating patient education every 6 months, or even more often, as in patients with asthma. Persuading adolescents to maintain these therapies is particularly difficult because they may believe that the compliance activities may cause them to lose the acceptance of their peers.

The Immune Deficiency Foundation is an important resource for education and support for patients and families with any primary immunodeficiency disease. For consultation, the foundation can be reached at 1-877-666-0866. The foundation's mailing address is 25 W Chesapeake Ave, Suite 206, Towson, MD 21204. Some states have local chapters.

The Jeffrey Modell Foundation at 747 3rd Ave, New York, NY 10017, also provides educational support and raises funds for research. The foundation can be reached at 1-800-JEFF-855.

For additional information on related diseases and conditions, see the articles Agammaglobulinemia and B-Cell and T-Cell Combined Disorders.

Previous
 
Contributor Information and Disclosures
Author

Terry W Chin, MD, PhD Associate Clinical Professor, Department of Pediatrics, University of California, Irvine, School of Medicine; Associate Director, Cystic Fibrosis Center, Attending Staff Physician, Department of Pediatric Pulmonology, Allergy, and Immunology, Memorial Miller Children's Hospital

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 Federation for Clinical Research, American Thoracic Society, California Society of Allergy, Asthma and Immunology, California Thoracic Society, Clinical Immunology Society, Los Angeles Pediatric Society, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

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 Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

James M Oleske, MD, MPH François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, Rutgers New Jersey Medical School; Professor, Department of Quantitative Methods, Rutgers 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 Hospice and Palliative Medicine, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, Pediatric Infectious Diseases Society, Arab Board of Family Medicine, American Academy of Pain Management, National Association of Pediatric Nurse Practitioners, Association of Clinical Researchers and Educators, American Academy of HIV Medicine, American Thoracic Society, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

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.

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

  2. Khan WN. Colonel Bruton's kinase defined the molecular basis of X-linked agammaglobulinemia, the first primary immunodeficiency. J Immunol. 2012 Apr 1. 188(7):2933-5. [Medline].

  3. York NR, de la Morena MT. 50 years ago in the journal of pediatrics: a decade with agammaglobulinemia. J Pediatr. 2012 May. 160:756.

  4. 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. 2009 Mar. 228(1):58-73. [Medline].

  5. 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].

  6. 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. 2007 Dec 21. 282(51):36953-60. [Medline].

  7. 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. 2008 Feb. 126(2):148-54. [Medline].

  8. 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].

  9. 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].

  10. Nasseri S, Sorouri R, Pourpak Z, Yeganeh M, Aghamohammadi A, Fiorini M, et al. Molecular characterization of Bruton's tyrosine kinase deficiency in 12 Iranian patients with presumed X-linked agammaglobulinemia. J Investig Allergol Clin Immunol. 2011. 21:572-4. [Medline].

  11. Vijayan V, Baumgart-Vogt E, Naidu S, Qian G, Immenschuh S. Bruton's tyrosine kinase is required for TLR-dependent heme oxygenase-1 gene activation via Nrf2 in macrophages. J Immunol. 2011 Jul 15. 187(2):817-27. [Medline].

  12. Abbott JK1, Ochs HD, Gelfand EW. Coding-region alterations in BTK do not universally cause X-linked agammaglobulinemia. J Allergy Clin Immunol. Nov 2013. 132:1246-8.

  13. 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. 2009 Jun. 46(10):2140-6. [Medline].

  14. 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. 2008 Feb. 45(4):1094-8. [Medline].

  15. Ramalho VD, Oliveira Júnior EB, Tani SM, Roxo Júnior P, Vilela MM. Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia. Braz J Med Biol Res. 2010 Sep. 43(9):910-3. [Medline].

  16. Qin X1, Jiang LP, Tang XM, Wang M, Liu EM, Zhao XD. Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients. World J Pediatr. Aug 2013. 9:273-7. [Medline].

  17. Merchant RH, Parekh D, Ahmad N, Madkaikar M, Ahmed J. X linked agammaglobulinemia: a single centre experience from India. Indian J Pediatr. Jan 2014. 81:92-94.

  18. 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. 2008 Feb 29. 49(1):28-36. [Medline].

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

  20. 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].

  21. Mohiuddin MS, Abbott JK, Hubbard N, Torgerson TR, Ochs HD, Gelfand EW. Diagnosis and evaluation of primary panhypogammaglobulinemia: a molecular and genetic challenge. J Allergy Clin Immunol. Jun 2013. 131:1717-8. [Medline].

  22. Jongco AM, Gough JD, Sarnataro K, Rosenthal DW, Moreau J, Ponda P, et al. X-linked agammaglobulinemia presenting as polymicrobial pneumonia, including Pneumocystis jirovecii. Ann Allergy Asthma Immunol. Jan 2014. 112:74-75. [Medline].

  23. Ariganello P1, Angelino G, Scarselli A, Salfa I, Della Corte M, De Matteis A, et al. Relapsing Campylobacter jejuni Systemic Infections in a Child with X-Linked Agammaglobulinemia. Case Rep Pediatr. 2013. 2013:735108.

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

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

  26. 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].

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

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

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

  30. Sukumaran S, Marzan K, Shaham B, Church JA. A child with x-linked agammaglobulinemia and enthesitis-related arthritis. Int J Rheumatol. 2011. 2011:175973. [Medline]. [Full Text].

  31. Behniafard N1, Aghamohammadi A, Abolhassani H, Pourjabbar S, Sabouni F, Rezaei N. Autoimmunity in X-linked agammaglobulinemia: Kawasaki disease and review of the literature. Expert Rev Clin Immunol. Feb 2012. 8:155-9. [Medline].

  32. Zhu Z1, Kang Y, Lin Z, Huang Y, Lv H, Li Y. X-linked agammaglobulinemia combined with juvenile idiopathic arthritis and invasive Klebsiella pneumoniae polyarticular septic arthritis. Clin Rheumatol. Feb 2014. Epub. [Medline].

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

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

  35. 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].

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

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

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

  39. 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. 2009 May. 29(3):352-6. [Medline].

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

  41. 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. 2007 Jul-Aug. 31(4):620-8. [Medline].

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

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

  44. Liu Y, Wu Y, Lam KT, Lee PP, Tu W, Lau YL. Dendritic and T cell response to influenza is normal in the patients with X-linked agammaglobulinemia. J Clin Immunol. 2012 Jun. 32(3):421-9. [Medline]. [Full Text].

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

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

  47. 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. 2006 May. 26(3):265-73. [Medline].

  48. 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. 2008 May. 152(2):274-9. [Medline].

  49. 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].

  50. 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. 2006 Apr. 117(4 Suppl):S525-53. [Medline].

  51. Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Clin Immunol. 2010 Oct. 137(1):21-30. [Medline].

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

  53. Berger M. Incidence of infection is inversely related to steady-state (trough) serum IgG level in studies of subcutaneous IgG in PIDD. J Clin Immunol. 2011 Oct. 31(5):924-6. [Medline].

  54. Beaute J, Levy P, Millet V, et al. Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies. Clin Exp Immunol. May/2010. 160:240-5. [Medline]. [Full Text].

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

  56. Quinti I, Pierdominici M, Marziali M, Giovannetti A, Donnanno S, Chapel H. European surveillance of immunoglobulin safety--results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol. 2002 Sep. 104(3):231-6. [Medline].

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

  58. Chen Y, Stirling RG, Paul E, Hore-Lacy F, Thompson BR, Douglass JA. Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies. J Allergy Clin Immunol. 2011 Jun. 127(6):1414-7. [Medline].

  59. Quinti I, Soresina A, Guerra A, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011 Jun. 31(3):315-22. [Medline].

  60. 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. 2009 Jan. 29(1):123-9. [Medline].

  61. 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. 1999 May. 134(5):589-96. [Medline].

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

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

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

  65. Cunningham-Rundles C. Autoimmunity in primary immune deficiency: taking lessons from our patients. Clin Exp Immunol. 2011 Jun. 164 Suppl 2:6-11. [Medline]. [Full Text].

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

  67. 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. 2007 Aug 15. 22(11):1664-6. [Medline].

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

  69. Staines Boone AT, Torres Martínez MG, López Herrera G, de Leija Portilla JO, Espinosa Padilla SE, Espinosa Rosales FJ, et al. Gastric Adenocarcinoma in the Context of X-linked Agammaglobulinemia : Case Report and Review of the Literature. J Clin Immunol. 34. Feb 2014:134-7. [Medline].

  70. 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. 2005 Sep. 116(3):690-7. [Medline].

  71. Gonzalo-Garijo MA, Sánchez-Vega S, Pérez-Calderón R, Pérez-Rangel I, Corrales-Vargas S, Fernández de Mera JJ, et al. Renal Amyloidosis in a Patient with X-linked Agammaglobulinemia (Bruton's Disease) and Bronchiectasis. J Clin Immunol. Jan 2014. 34:119-22. [Medline].

  72. 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. 2004 Apr. 113(4):783-5. [Medline].

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

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

  75. 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. 2004 Mar 8. 40(2):113-8. [Medline].

  76. 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. 2005 Jan. 129(1):100-3. [Medline].

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

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

  79. 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. 2001 Aug 7. 135(3):165-74. [Medline].

  80. Merchant RH, Parekh D, Ahmad N, Madkaikar M, Ahmed J. X linked agammaglobulinemia: a single centre experience from India. Indian J Pediatr. Jan 2014. 81:92-94.

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

  82. Ní Gabhann J, Spence S, Wynne C, Smith S, Byrne JC, Coffey B, et al. Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-? production by natural killer cells. Clin Immunol. 2012 Mar. 142(3):373-82. [Medline].

  83. 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. 2002 Sep. 104(3):221-30. [Medline].

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

  85. Staines Boone AT1, Torres Martínez MG, López Herrera G, de Leija Portilla JO, Espinosa Padilla SE, Espinosa Rosales FJ, et al. Gastric Adenocarcinoma in the Context of X-linked Agammaglobulinemia : Case Report and Review of the Literature. J Clin Immunol. Feb 2014. 34:134-7. [Medline].

  86. 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 Process pH Additives (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 Concentrations IgA Content mcg/mL
Carimune NF



(ZLB Behring)



Kistler-Nitschmann fractionation, pH 4 incubation, nanofiltration 6.4-6.8 6% solution: 10% sucrose, < 20 mg NaCl/g protein Lyophilized powder 3, 6, 9, 12% Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization 5.1-6 Sucrose free, contains 5% D-sorbitol Liquid 5% < 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.1 0.25 M glycine Ready-for-use liquid 10% 37
Gammar-P IV



(ZLB Behring)



Cohn-Oncley fraction II/III, ultrafiltration, pasteurization 6.4-7.2 5% solution: 5% sucrose, 3% albumin, 0.5% NaCl Lyophilized powder 5% < 20
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation 4-4.5 Contains no sugar, contains glycine Liquid 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 4.8-5.1 Contains sorbitol (40 mg/mL); do not administer if fructose intolerant Ready-for-use solution 5% < 10
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III, ultrafiltration, pasteurization 6.4-7.2 5% solution: 5% glucose, 0.3% NaCl Lyophilized 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 6.4-7.2 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose Lyophilized 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 pasteurization 5.1-6 10% maltose Liquid 5% 200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation, pH 4 incubation, trace pepsin, nanofiltration 6.6 Per gram of IgG: 1.67 g sucrose,< 20 mg NaCl Lyophilized powder 3, 6, 9, 12% 720
Privigen



(CSL Behring)



pH 4 incubation, octanoic acid fractionation, depth filtration, and virus filtration 4.6-5 10% solution; Preservative-free and sucrose- and maltose-free Ready-to-use solution 10% 25
Table 2. Immune Globulin, Subcutaneous
Brand(Manufacturer) Manufacturing Process pH Additives Parenteral Form and Final Concentrations IgA Content mcg/mL
Vivaglobin



(ZLB Behring)



Cold ethanol fractionation, pasteurization 6.4-7.2 2.25% glycine, 0.3% NaCl Liquid 16% (160 mg/mL) < 50 mcg/mL
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.