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T-Cell Disorders Treatment & Management

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Jan 12, 2016
 

Approach Considerations

Exploration of mutations and analysis of cellular changes related to lymphocyte defects and immune dysregulation has fueled the development of novel treatment options for some primary T-cell disorders that might otherwise by fatal.[16]

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Medical Care

Sinopulmonary infections with common viral and bacterial agents are characteristic of partial T-cell disorders. Conventional therapy appropriate for the immunologically healthy host is administered, although patients with T-cell defects characteristically have more prolonged and severe clinical courses. Prophylaxis against infection by respiratory syncytial virus (RSV) using RSV-polyclonal immunoglobulin or the humanized monoclonal antibody, palivizumab, is specifically indicated in patients with T-cell disorders. Mucocutaneous candidiasis is more frequent but is conventionally treated in patients, and the disease uncommonly disseminates.

Bone marrow transplantation must be offered early in infancy to patients with Wiskott-Aldrich syndrome (WAS) to ensure better outcome. In addition, transplantation is the only effective treatment in most patients with Chediak-Higashi syndrome (CHS) and is indicated prior to development of the accelerated phase. Patients with DiGeorge syndrome (DGS) rarely have complete absence of T-cell function; these few patients require stem cell reconstitution, usually via bone marrow transplantation.

Routine childhood immunizations are usually indicated because patients with partial T-cell defects, even those with abnormalities in immunoglobulin levels, often respond with adequate specific antibody titers, although the levels may be lower than normal. However, administration of the oral live-attenuated poliovirus vaccine is contraindicated and should be replaced with the inactivated poliovirus vaccine. As a result of the frequency of bacterial sinopulmonary infections, administration of the conjugated pneumococcal vaccine (Prevnar) is particularly important.

Usually, treatment in persons with autoimmune disorders mirrors that for hosts who are immunocompetent. However, infectious complications pose a greater risk in patients with T-cell disorders who receive systemic steroids and other immunosuppressive drugs.

Overproduction of cytokines by T cells and other effector cells of the immune system can be controlled through use of anticytokine monoclonal antibodies, such as anti–tumor necrosis factor (TNF)–α (infliximab), for inflammatory bowel disease.

Insulin-dependent diabetes mellitus (IDDM), hypoadrenalism, hypothyroidism, glomerulonephritis, and autoimmune enteropathy present in patients at unusually young ages, typically in patients younger than 1 year who have immune dysregulation/autoimmunity disorders.

Patients with WAS and older patients who have chromosomal breakage syndromes (CBSs) have a high risk of malignancy. Chemotherapy in patients with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) is not usually tolerated at conventional doses because of DNA instability. Thus, lower doses and longer intervals between doses are usually used.

Gene therapy is being studied as a possible alternative to allogeneic hematopoietic stem cell transplantation for the treatment of severe combined immunodeficiency (SCID),[17] as well as a treatment for WAS.[18, 19]

Several drugs that block the lymphocyte voltage-gated potassium channel, kv1.3, as well as biologic therapies, are being explored as autoimmune disease treatments.[20, 21]

Graft versus host disease (GVHD) has been prevented successfully in mice through ex vivo selection and expansion of CD4(+)CD25(+) immunoregulatory T cells, specific for recipient alloantigens.[22]

Mesenchymal stem cells have shown some promise in enhancing engraftment and both preventing and treating GVHD in bone marrow transplant recipients.[23]

Antithymocyte globulin has been shown to reduce acute and chronic GVHD in randomized trials.[24]

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Surgical Care

With the exception of cardiac procedures in patients with DGS, surgery is not usually required for patients with partial T-cell disorders.

Splenectomy has been used to control autoimmune hemolytic anemia and thrombocytopenia in patients with WAS and immune dysregulation/autoimmunity syndromes. In patients with WAS and Fas and Fas ligand deficiencies, overwhelming postsplenectomy sepsis has occurred despite immunization and antibiotic prophylaxis directed against Streptococcus pneumoniae.

Tumor-stage vulvar mycosis fungoides responded to local low-dose radiotherapy (Bakar et al, 2014).

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Consultations

Clinical immunologists and geneticists are integral to the evaluation and treatment in patients with partial T-cell disorders.

Intervention performed by neurologists is important in patients with CBSs and CHS.

Physical therapists and rehabilitation specialists are critical to achieving optimal functioning in patients with CBSs and CHS.

Autoimmune disorders are best controlled with the help of collaboration by hematologists, endocrinologists, and gastroenterologists.

The malignancies in CBSs may require alteration of chemotherapeutic regimens because of the increased DNA instability of host cells.

When a T-cell disorder is suspected, the Immune Deficiency Foundation offers a consultation service for physicians. Laboratories in Seattle (the University of Washington), Boston (Children's Hospital Boston), and New York City (The Jeffrey Modell Foundation) are funded to provide molecular analysis or can assist in contacting other research facilities.

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Diet

As with other primary immunodeficiencies, supplemental nutrition can be an essential component of care for the patient with chronic enteropathy or chronic infection.

Unfortunately, many patients remain thin with short stature or become wasted.

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Activity

The goal of care is to optimize daily functioning. Care to minimize exposure to certain viruses (eg, RSV, varicella) is important, but complete isolation is not recommended for patients with partial T-cell disorders.

Patients with WAS and CHS who have increased bleeding tendencies must be educated to avoid trauma and, especially, to wear helmets during certain activities.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Robert Y Lin, MD Professor, Department of Medicine, New York Medical College; Chief, Allergy and Immunology, and Director of Utilization Review, Department Medicine, New York Downtown Hospital

Robert Y Lin, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, New York Allergy & Asthma Society

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.

David J Valacer, MD 

David J Valacer, 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 Thoracic Society, New York Academy of Sciences

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

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.

Acknowledgements

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

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This patient was diagnosed with ataxia telangiectasia (AT) when she presented at age 6 years. The family was concerned about the increased frequency of sinusitis during the past winter, and she was noted to have poor balance. Findings in her eyes had been explained as conjunctivitis since age 4 years.
A prominent site for telangiectasia in classic ataxia telangiectasia is the pinna.
Malformation of the pinna
Giant lysosomes.
Table. Immune Globulin, Intravenous [25, 26, 27, 28]
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



(CSL 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% 720
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 0.25M glycine Ready-for-use liquid 10% 37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation 4-4.5 Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine Liquid 10% 46
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 Liquid 10%



(CSL Behring)



Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration 4.6-5 L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) Ready-for use liquid 10% < 25
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