T-Cell Disorders Clinical Presentation

Updated: Jun 12, 2020
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Presentation

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. [14]

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 telangiecta 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 ata A 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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Physical Examination

Cutaneous granulomas are sometimes evident as non-infectious findings may precede the diagnosis of ataxia-telangiectasia, combined variable immunodeficiency, and severe combined immunodeficiency. [15, 16]

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