T-Cell Disorders Clinical Presentation

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: May 16, 2011
 

History

Unusually severe common viral infections (eg, respiratory syncytial virus [RSV], enterovirus, rotavirus), mucocutaneous candidiasis, diarrhea, and eczematous or erythrodermatous rashes should prompt suspicion of a T-cell disorder. Failure to thrive and cachexia are late signs of a T-cell defect. Opportunistic infection develops more commonly in an infant who has become wasted, although it may be the presenting illness.

Late diagnosis of a partial T-cell defect may occur in patients with DiGeorge syndrome (DGS) when the facial anomalies are subtle and cardiac lesions are absent. These individuals have recurrent respiratory infections consisting of sinusitis and viral infections. In addition, patients have more extensive mucocutaneous candidiasis than anticipated in a healthy host taking antibiotics.

Engrafted maternal T cells rarely may persist, leading to partial constitution of immune function and delayed clinical presentation of SCID.[7]

In patients with ataxia telangiectasia (AT), late diagnosis is often based on the progressive loss of mobility and the appearance of telangiectasia in children aged approximately 4-5 years.

A diagnosis of Wiskott-Aldrich syndrome (WAS) may be delayed until recurrent sinopulmonary infections develop if petechiae and bloody diarrhea are minor and intermittent and if eczema is misinterpreted as severe atopic dermatitis. Additionally, more than 70% of patients with WAS have at least one autoimmune complication.

Patients with Chediak-Higashi syndrome (CHS) are often treated for recurrent otitis, sinusitis, and lymphadenitis caused by staphylococci and streptococci before the massive lymphadenopathy and hepatosplenomegaly make the diagnosis obvious in the accelerated phase.

Epstein-Barr virus (EBV) infection is the predominant lethal infection in X-linked lymphoproliferative disease (XLP), and EBV infection is usually associated with development of the accelerated phase of CHS.

The diagnosis of insulin-dependent diabetes mellitus (IDDM) and diarrhea in a male infant younger than 1 year raises the possibility of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. IDDM and enteropathy are also components of the clinical features in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

Lymphadenopathy and hepatosplenomegaly characterize mutations in the genes coding for CD3 complex and CD95/Fas.

Patients with WAS in whom the immune system is not reconstituted by hematopoietic stem cell transplantation usually die by the third-fourth decade of life from malignancies; lymphoid and CNS tumors are most common.

Patients with AT and Nijmegen breakage syndrome (NBS) are at a higher risk for malignancies, usually lymphoid, that increases with age.

Neurologic disorders are increasingly reported in patients with partial T-cell disorders. Progressive neurologic dysfunction is well known in patients with chromosomal breakage syndromes (CBSs), such as AT, NBS, and in CHS. Patients with DGS have learning and behavioral dysfunction that becomes more apparent at school age. Seizure disorders frequently accompany immune dysregulation/autoimmunity syndromes such as IPEX caused by FoxP3 gene mutation .

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Physical

The physical examination features of DGS, WAS, and AT are presented in detail in other respective articles.

Rash often occurs in infants with a T-cell disorder, commonly as a generalized eczema or erythroderma. Urticarial rashes and cutaneous vasculitis are present in CD95/Fas and Fas ligand deficiencies as well as caspase 10 defects. Ectodermal dystrophy characterizes APECED syndrome.

Patients with AT have telangiectasia of the conjunctiva and pinna; these features present after the diagnosis should already have been confirmed by the presence of ataxia and infections. See the images below.

This patient was diagnosed with ataxia telangiectaThis 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 ataA prominent site for telangiectasia in classic ataxia telangiectasia is the pinna. Malformation of the pinna Malformation of the pinna

Candidiasis is a common feature of partial and complete T-cell disorders. In partial T-cell disorders (eg, DGS, WAS, APECED syndrome, IPEX syndrome) dissemination is unlikely, even when the autoimmune disease is treated with immunosuppressive agents. Disseminated invasive candidiasis suggests severe combined immunodeficiency (SCID) or a phagocytic disorder.

Patients with the classic presentation have a complete absence of T cells (ie, SCID) and lack peripheral lymphoid tissue. However, patients with partial T-cell disorders often have palpable lymph nodes.

Lymphadenopathy and hepatosplenomegaly may be progressive in immune dysregulation/autoimmunity syndromes, such as Fas and Fas ligand deficiencies and mutations in the gene coding for CD3 complex. Lymphadenopathy suggests the possibility of lymphoma or leukemia in older patients with WAS and CBSs.

Neurologic deterioration with hypotonia and progressive ataxia may occur before infection, raising a suspicion of immunodeficiency in patients with AT and NBS.

Bleeding in patients with WAS is a result of impaired platelet aggregation with smaller platelet size and numbers of platelets.

In infants, the first sign of WAS is often bloody diarrhea that occurs before petechiae and epistaxis following introduction of solid food.

In the accelerated phase, CHS is accompanied by bleeding.

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Causes

Many of the exact functions of the gene products that are mutated in partial T-cell disorders have yet to be elucidated.

For a more complete discussion of the genes responsible for DGS, AT, WAS, and CHS, see Pathophysiology and the specific articles for each disorder.

CHS is caused by mutations in the gene encoding for the lysosomal-trafficking regulator. This mutation leads to abnormal distribution of lysosomal proteins in phagocytes (impairing bactericidal activity), in melanosomes (explaining partial albinism), and in neurologic function and to cytotoxicity by T cells and natural killer (NK) cells, predisposing patients to aberrant responses to EBV and leading to the accelerated phase.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and 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 and American Federation for Medical Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Terry W Chin, MD, PhD  Associate Director, Pediatric Allergy/Immunology/Pulmonology, Miller Children's Hospital, Long Beach Memorial Medical Center; Associate Professor, Department of Pediatrics, University of California, Irvine, School of Medicine

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 Thoracic Society, California Thoracic Society, Clinical Immunology Society, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

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  Consulting Staff, Hoffman La Roche Pharmaceuticals

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, and New York Academy of Sciences

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School

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 Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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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[16, 17, 18, 19]
Brand(Manufacturer)Manufacturing ProcesspHAdditives (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 ConcentrationsIgA Content mcg/mL
Carimune NF



(CSL Behring)



Kistler-Nitschmann fractionation; pH 4 nanofiltration6.4-6.86% solution: 10% sucrose, < 20 mg NaCl/g proteinLyophilized powder 3%, 6%, 9%, 12%720
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose free, contains 5% D-sorbitolLiquid 5%< 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25M glycineReady-for-use liquid 10%37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycineLiquid 10%46
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III; ultrafiltration; pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized 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 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophilized 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 pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation; pH 4 incubation; trace pepsin; nanofiltration6.6Per gram of IgG: 1.67 g sucrose, < 20 mg NaClLyophilized 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 filtration4.6-5L-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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