B-Cell and T-Cell Combined Disorders Treatment & Management

  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Aug 26, 2014
 

Medical Care

As with other immunodeficiencies, aggressive antibiotic administration and supportive care may prolong the patient's survival, though no current therapy cures ataxia-telangiectasia (AT). Careful observation for the early development of AT is indicated because patients with T-cell deficiency have an increased susceptibility to develop malignancies. Likewise, regular determination of serum autoantibody level and constant clinical evaluation for endocrinopathy (eg, hypoparathyroidism, hypoadrenalism, diabetes) is needed in patients with chronic mucocutaneous candidiasis (CMC).

Unlike other combined immunodeficiency syndromes, AT and CMC do not generally warrant gamma-globulin replacement therapy because of the marked variation in humoral immunodeficiency with the concomitant variable susceptibility to infections. On the other hand, an individual patient may benefit from such treatment. If a trial of intravenous immunoglobulin (IVIG) is considered in these patients, the dosage is 400-600 mg/kg every 2-4 weeks for 6 months. A high dosage is indicated in those with bronchiectasis. Monitor the patient's clinical response rather than specific serum immunoglobulin G (IgG) levels.

Bone marrow transplantation is difficult to justify because of potential adverse effects of cellular radiosensitivity in patients with AT. Transplantation is also unlikely to alter the progressive neurologic symptoms of the disease. The present authors know of no report of successful bone marrow transplantation in a patient with CMC.

The Primary Immune Deficiency Treatment Consortium analyzed the results of hematopoietic stem cell transplantation in children with SCID. Researchers collected data from 240 infants who had received transplants at 25 centers from 2000-2009 and concluded that transplants from donors other than matched siblings resulted in high survival rates if the infants were identified before infection developed. Asymptomatic infants responded well to all graft sources.[15]

Use of thymic hormones (eg, thymosin) offers promise, but, to the author's knowledge, no clinical studies have been conducted.

Irradiation of cellular blood products is indicated in patients with AT and CMC to prevent transfusion-associated graft versus host disease.

Treatment of patients with AT who also have malignancies requires extremely careful planning and caution in the use of chemotherapy because of their increased chemosensitivity.

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Consultations

Because patients with AT and Nijmegen breakage syndrome (NBS) have an increased risk of developing malignancy, careful monitoring is required by a hematologist-oncologist. Because patients with CMC may be at risk of developing various endocrinopathies, careful monitoring is required by an endocrinologist. Thymoma may also develop in adulthood. Regular screening by a gastroenterologist has been suggested for patients with CMC with a history of recurrent candidal esophagus or a family history positive for esophageal or oral carcinoma.

Primary care physicians who are less experienced in interpreting results of immune function tests should refer patients to an immunologist.

Refer parents of children with AT and CMC to a genetic counselor because they are at risk for affected additional offspring.

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Diet

The poor growth in patients with AT and NBS has not been shown to respond to nutritional intervention.

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Activity

Because of the increased sensitivity to radiation in patients with AT or NBS, advise these patients to avoid excessive sun exposure and to use sunscreens when outdoors.

The typical patient with AT usually requires a wheelchair for mobility by early teenage years.

For patients with CMC, good oral hygiene and aggressive treatment of oral and esophageal candidiasis are needed.

Avoidance of additional risk factors for oral and esophageal cancer such as cigarette smoking and excessive alcohol consumption may also be warranted.

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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.

Coauthor(s)

Noufa Alonazi, MD, MBBS Allergy and Immunology Postdoctoral Fellow, Department of Pediatrics, Loma Linda University and Medical Center

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.

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.

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Telangiectasia.
Radiograph shows an 8-month-old boy who required ventilatory support for bilateral pneumonia and who received intravenous antibiotics. The patient recovered and returned home.
Chest radiograph in an 8-month-old boy 2 weeks after he was treated for bilateral pneumonia. The patient returned to the emergency department with a fever and breathing problems.
Chest radiograph in a 9-month-old boy. The patient developed breathing problems 1 month after recovering from a second hospitalization for pneumonia. By this time, serum immunoglobulin levels from the second hospitalization were in the patient's record and showed an immunoglobulin G level of 156 mg/dL and undetectable immunoglobulin A and immunoglobulin M levels. Subsequent bronchoscopy showed the presence of Pneumocystis carinii and cytomegalovirus.
Telangiectasia of conjunctivae.
A 5-year-old boy with thrush.
Table. Intravenous Immunoglobulin Therapy [17, 18, 19, 20]
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, 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 ultra centrafiltration 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, trace pepsin, nanofiltration 6.6 Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl Lyophilized powder 3%, 6%, 9%, 12% 720
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