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Combined B-Cell and T-Cell Disorders Follow-up

  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Apr 14, 2015
 

Further Outpatient Care

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  • Regularly monitor patients for the following parameters:
    • Growth and development
    • Chest radiographs
    • Pulmonary function
    • Immunoglobulin trough levels
      • levels greater than or equal to 400 mg/dL are considered satisfactory. Occasionally, levels greater than 500 mg/dL are required to clear certain viral infections, such as enterovirus meningoencephalitis.
      • Trough levels may need to be titrated in individual patients to determine the level that is needed to prevent recurrent infection.
  • Liver function tests should be performed. If abnormalities are identified, imaging studies of the liver and biliary tree are necessary to exclude malignancies or sclerosing cholangitis (the latter is observed in patients with XHM).
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Inpatient & Outpatient Medications

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  • Once initiated, IVIG therapy can be self-administered by the patient.
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Transfer

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  • Specialists in the diagnosis and treatment of these patients should be consulted for their initial evaluation and treatment.
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Deterrence/Prevention

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  • The liberal use of antibiotics helps to decrease the frequency of infections in these patients. Some experts use a rotating regimen of antibiotics on a monthly basis.
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Complications

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  • Bronchiectasis and cor pulmonale complicate chronic/recurrent lower respiratory tract infections.
  • Hearing loss due to chronic otitis media or meningoencephalitis may affect as many as one third of patients with XLA.
  • The risk of GVHD is high in patients with SCID because of their inability to reject foreign antigens.
  • EBV-associated smooth muscle tumors may occur in patients who are partially reconstituted after bone marrow transplantation for SCID and who may not require surgery or chemotherapy.[22]
  • Central nervous system viral infection is one of the most potentially devastating complications of immunodeficiency, but this is a rare presentation in patients with SCID.
  • Complications related to IVIG therapy include the following:
    • Increased serum viscosity and thromboembolic events, increased risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d postinfusion) can occur.
    • The most common adverse reactions are nonanaphylactic in nature and are characterized by back and abdominal pain, nausea, vomiting, chills, fever, and myalgias. Discontinue the infusion until the symptoms subside; then restart at a slower rate.
    • True anaphylactic reactions are rare and occur seconds to hours after the infusion is started. Typical symptoms consist of flushing, facial swelling, dyspnea, and hypotension. Stop the infusion, and administer epinephrine, steroids, and antihistamines together.
    • The risk of renal tubular necrosis is increased in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease.
    • Transmission of hepatitis C virus (HCV) is much less common now than in the past. Most patients who are HCV RNA–positive contracted their infection in the 1980s when serologic testing of blood donors for this infection was not available. Chronic liver disease in these patients is characterized by a severe clinical course, particularly in those with CVID.
      • Hepatitis B virus (HBV) and hepatitis G virus (HGV) seem to play minor roles in the pathogenesis of chronic liver disease in these patients.
      • A milder form of chronic liver disease with negative serology for HCV, HBV, and HGV infections has been described in these patients. This form occurs, on average, 36 months after the beginning of IVIG therapy, and it is thought to be related to immune phenomena or to a viral infection not yet described.
      • A few non-HCV, non-HBV, and non-HGV patients have a particularly severe course, and granulomatous disease of the liver has been identified in most of them.
      • Lymphoma, especially Burkitt lymphoma, has been reported in patients with ADA deficiency, including those who received prolonged PEG-ADA replacement therapy.
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Prognosis

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  • Without treatment, most of the patients with combined B-cell and T-cell disorders die within the first 6 months.
  • Patients who are well nourished, uninfected, and younger than 6 months before transplantation have the best outcomes.
  • Patients with SCID barely survive without stem cell reconstitution. However, gene therapy is an alternative for those cases in which donors are unavailable.
  • Patients with less severe mutations in the ADA gene have survived into adulthood.
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Patient Education

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  • Inform patients and their families about the risk of overwhelming infection and the need for immediate intervention.
  • Encourage the use of antibiotics in case symptoms of infection arise, along with immediate referral to the nearest medical facility for evaluation.
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Contributor Information and Disclosures
Author

Francisco J Hernandez-Ilizaliturri, MD Associate Professor of Medicine, Department of Medicine, Assistant Professor of Immunology, Department of Immunology, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

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, American Society of Hematology

Disclosure: Nothing to disclose.

David Claxton, MD Professor of Medicine, Department of Internal Medicine, Section of Hematology-Oncology, Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Mohammad Muhsin Chisti, MD, FACP Assistant Professor of Hematology and Oncology, Karmanos Cancer Institute, Michigan State University College of Human Medicine

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

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, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

James O Ballard, MD Kienle Chair for Humane Medicine, Professor, Departments of Humanities, Medicine, and Pathology, Division of Hematology/Oncology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

James O Ballard, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American Society of Hematology

Disclosure: Nothing to disclose.

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Table 1. Classification of SCID
PathophysiologyCells AffectedInheritanceGenes Involved
Premature cell deathT, B, NKARADA
Defective cytokine–dependent survival signalingT, NKAR



γ c type-XL



JAK3, IL7RA (T cells only), γ c
Defective V(D)J rearrangementT, BARRAG1, RAG2, Artemis
Defective pre-TCR and TCR signalingTARCD3 δ, CD3 ζ, CD3 ε,



CD45



AR = autosomal recessive; JAK3 =Janus tyrosine kinase 3; RAG1, RAG2 = recombinase activating gene 1 and 2, respectively; TCR = T-cell receptor; XL = X-linked; V(D)J = variable diversity joining.
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