eMedicine Specialties > Hematology > Disorders of Lymphocytic Function

Pure B-Cell Disorders: Treatment & Medication

Author: Issam Makhoul, MD, Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences
Coauthor(s): David Claxton, MD, Assistant Professor, Department of Internal Medicine, Section of Hematology-Oncology, Hershey Medical Center, Pennsylvania State University; Witold Rybka, MD, Professor of Medicine and Pathology, Penn State Hershey College of Medicine, Director, Bone Marrow Transplant Program, Penn State Hershey Medical Center; Hanan Makhoul, MD, Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Contributor Information and Disclosures

Updated: Nov 4, 2009

Treatment

Medical Care

  • IVIG replacement therapy is the treatment of choice for most primary B-cell disorders with hypogammaglobulinemia, including XLA, CVID, immunodeficiency with thymoma, and most of the combined immunodeficiencies. Do not administer IVIG to patients with IgG subclass deficiency unless they do not produce antibodies and do not respond to prophylactic antibiotics.
    • Quartier et al reported on 31 XLA patients treated early in life with IVIG.9 The higher the trough level of immunoglobulin, the lower the incidence of acute bacterial infections requiring hospitalization, with the best results obtained with levels of more than 800 mg/dL and the worst results with levels of less than 500 mg/dL. However, chronic bronchitis and sinusitis were not prevented by this treatment.
    • IVIG is not indicated in persons with selective THI.
    • IVIG is not indicated for IgG subclass deficiency unless a broader deficiency of antibody production is present.
    • For selective IgA deficiency, IVIG therapy is not indicated. Oral administration of immunoglobulin may improve chronic diarrhea. Immunoglobulin preparations containing low levels of IgA and washed blood products should be used in cases of concomitant IgG deficiency.
    • High doses of IVIG or intrathecal immunoglobulin may be beneficial in enteroviral meningoencephalitis.
  • Do not immunize these patients with live attenuated vaccines.
  • Focus efforts on the treatment of infections, allergic reactions, and autoimmune and GI diseases. Aggressive and prolonged antibiotic therapy covering S pneumoniae and H influenzae is indicated. Prophylactic antibiotic therapy has been recommended for patients with frequent infections. A course of metronidazole may result in dramatic improvement of the diarrhea and, to a certain extent, of malabsorption syndrome. Prophylactic antibiotic therapy may significantly decrease the incidence of infections.
  • Interleukin-2 may improve in vitro lymphocyte function in persons with CVID. However, because of limited use in humans, no final conclusions can be made regarding its efficacy.
  • Parenteral vitamin B-12 is used in persons with pernicious anemia.

Activity

Encourage physical activity.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Immunoglobulins

Provide immediate passive immunity. Replacement therapy in antibody deficiency states.


Immune globulin, intravenous (Gamimune, Gammagard, Sandoglobulin, Gammar-P)

Induces elevated antiviral or antibacterial antibody titers for 1 mo. May increase CSF IgG (10%).

Adult

200-400 mg/kg IV q3-4wk to achieve a trough level of >400 mg/dL; trough levels >500 mg/dL do not necessarily improve infection control (except in certain chronic infections) but may significantly increase cost

Pediatric

Not established

Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine

Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies

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 an 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 (2-5 d postinfusion to 30 d); most common adverse reactions are nonanaphylactic and are characterized by back and abdominal pain, nausea, vomiting, chills, fever, and myalgias; stop infusion until symptoms subside, then restart at a slower rate; true anaphylactic reactions are rare and occur seconds to hours after infusion is started; typical symptoms consist of flushing, facial swelling, dyspnea, and hypotension; stop infusion and administer epinephrine, steroids, and antihistamines together; increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include 6-fold increase in ESR for 2-3 wk and apparent hyponatremia

More on Pure B-Cell Disorders

Overview: Pure B-Cell Disorders
Differential Diagnoses & Workup: Pure B-Cell Disorders
Treatment & Medication: Pure B-Cell Disorders
Follow-up: Pure B-Cell Disorders
References
Further Reading
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References

  1. O'Gorman MR. Measurement of CD40 ligand (CD154) expression on resting and in vitro-activated T cells. Curr Protoc Cytom. May 2001;Chapter 6:Unit 6.7. [Medline].

  2. Van Hoeyveld E, Zhang PX, De Boeck K, Fuleihan R, Bossuyt X. Hyper-immunoglobulin M syndrome caused by a mutation in the promotor for CD40L. Immunology. Apr 2007;120(4):497-501. [Medline].

  3. Bussone G, Mouthon L. Autoimmune manifestations in primary immune deficiencies. Autoimmun Rev. Feb 2009;8(4):332-6. [Medline].

  4. Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol. May 2008;28 Suppl 1:S62-6. [Medline].

  5. Levy J, Espanol-Boren T, Thomas C, et al. Clinical spectrum of X-linked hyper-IgM syndrome. J Pediatr. Jul 1997;131(1 Pt 1):47-54. [Medline].

  6. Poliani PL, Facchetti F, Ravanini M, Gennery AR, Villa A, Roifman CM, et al. Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. Blood. Jul 2 2009;114(1):105-8. [Medline].

  7. McCusker C, Hotte S, Le Deist F, Hirschfeld AF, Mitchell D, Nguyen VH, et al. Relative CD4 lymphopenia and a skewed memory phenotype are the main immunologic abnormalities in a child with Omenn syndrome due to homozygous RAG1-C2633T hypomorphic mutation. Clin Immunol. Jun 2009;131(3):447-55. [Medline].

  8. Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. Mar 4 1999;340(9):692-702. [Medline].

  9. 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].

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

  11. Kainulainen L, Varpula M, Liippo K, et al. Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. Nov 1999;104(5):1031-6. [Medline].

  12. Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med. Oct 15 1997;127(8 Pt 1):613-7. [Medline].

  13. Ballow M, O'Neil KM. Approach to the Patient With Recurrent Infections. In: Middleton E Jr, Reed CM, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles & Practice. 5th ed. St. Louis, Mo: Mosby-Year Book; 1998:. 735-59.

  14. Behrman RE, Kliegman RM, Jenson HB, eds. Primary B-Cell diseases. In: Nelson's Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders; 2000:. 596-606.

  15. Berger M. Goals of therapy in antibody deficiency syndromes. J Allergy Clin Immunol. Nov 1999;104(5):911-3. [Medline].

  16. Bezrodnik L, Samara R, Krasovec S, et al. Progressive multifocal leukoencephalopathy in a patient with hypogammaglobulinemia. Clin Infect Dis. Jul 1998;27(1):181-4. [Medline].

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  19. Dreskin SC, Goldsmith PK, Gallin JI. Immunoglobulins in the hyperimmunoglobulin E and recurrent infection (Job''s) syndrome. Deficiency of anti-Staphylococcus aureus immunoglobulin A. J Clin Invest. Jan 1985;75(1):26-34. [Medline].

  20. Hadzic N, Pagliuca A, Rela M, et al. Correction of the hyper-IgM syndrome after liver and bone marrow transplantation. N Engl J Med. Feb 3 2000;342(5):320-4. [Medline].

  21. Jones AM, Gaspar HB. Immunogenetics: changing the face of immunodeficiency. J Clin Pathol. Jan 2000;53(1):60-5. [Medline].

  22. Kohn DB. Gene therapy for genetic haematological disorders and immunodeficiencies. J Intern Med. Apr 2001;249(4):379-90. [Medline].

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

  24. Sanna PP, Burton DR. Role of antibodies in controlling viral disease: lessons from experiments of nature and gene knockouts. J Virol. Nov 2000;74(21):9813-7. [Medline].

  25. Satterthwaite AB, Witte ON. The role of Bruton''s tyrosine kinase in B-cell development and function: a genetic perspective. Immunol Rev. Jun 2000;175:120-7. [Medline].

  26. Scholl PR, O''Gorman MR, Pachman LM, et al. Correction of neutropenia and hypogammaglobulinemia in X-linked hyper- IgM syndrome by allogeneic bone marrow transplantation. Bone Marrow Transplant. Dec 1998;22(12):1215-8. [Medline].

  27. Smith JK, Krishnaswamy GH, Dykes R, et al. Clinical manifestations of IgE hypogammaglobulinemia. Ann Allergy Asthma Immunol. Mar 1997;78(3):313-8. [Medline].

  28. Sneller MC. Common variable immunodeficiency. Am J Med Sci. Jan 2001;321(1):42-8. [Medline].

  29. Tarr PE, Sneller MC, Mechanic LJ, et al. Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore). Mar 2001;80(2):123-33. [Medline].

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Further Reading

Related eMedicine topics
 Combined B-Cell and T-Cell Disorders
Pure Red Cell Aplasia
X-linked Immunodeficiency With Hyper IgM
Omenn Syndrome
Bruton Agammaglobulinemia

Clinical guidelines
 Practice parameter for the diagnosis and management of primary immunodeficiency.
American Academy of Allergy, Asthma and Immunology - Medical Specialty Society
American College of Allergy, Asthma and Immunology - Medical Specialty Society
Joint Council of Allergy, Asthma and Immunology - Medical Specialty Society. 1995 Aug 31 (revised 2005 May). 63 pages. NGC:004445

Clinical trials
 Epigenetic Markers of B-Cell Function in Low Birth Weight Infants

Genetic Basis of Immunodeficiency

Molecular and Clinical Studies of Primary Immunodeficiency Diseases

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Keywords

pure B-cell disorders, immunodeficiency, immune deficiency disorder, hyper-IgM, lymphopoiesis, immunodeficiencies, lymphoma, leukemia, B-cell immunodeficiency, B-cell immunodeficiencies, primary lymphopoiesis, secondary lymphopoiesis, IgA deficiency, immunoglobulin A deficiency, selective immunoglobulin M deficiency, selective IgM deficiency, Wiskott-Aldrich syndrome

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Contributor Information and Disclosures

Author

Issam Makhoul, MD, Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences
Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

David Claxton, MD, Assistant Professor, Department of Internal Medicine, Section of Hematology-Oncology, Hershey Medical Center, Pennsylvania State University
Disclosure: Nothing to disclose.

Witold Rybka, MD, Professor of Medicine and Pathology, Penn State Hershey College of Medicine, Director, Bone Marrow Transplant Program, Penn State Hershey Medical Center
Witold Rybka, MD is a member of the following medical societies: American Society of Hematology and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Hanan Makhoul, MD, Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Charles S Greenberg, MD, Director of Thrombosis and Transglutaminase Research Laboratory, Professor, Departments of Pathology and Medicine, Division of Hematology/Oncology, Duke University Medical Center
Charles S Greenberg, MD is a member of the following medical societies: American Society of Hematology and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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