Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX) Workup

Updated: Aug 06, 2019
  • Author: Taylor Banks, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Workup

Laboratory Studies

Molecular genetic testing for immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome can be performed by DNA sequencing of the FOXP3 gene and mutation analysis. [21] Sixty percent of patients with IPEX syndrome have an identifiable mutation in FOXP3. Patients with IPEX-like conditions with no identifiable mutation in FOXP3 may have mutations in the regulatory sequences in the FOXP3 gene or in pathways related to regulatory T-cell development or function. [19, 20]

While genetic testing modalities remain the criterion standard, one paper does highlight autoantibody markers to harmonin and villin as a possible diagnostic tool for IPEX syndrome; however, more research is needed. [22, 23]

Although not diagnostic, other laboratory tests may support the diagnosis of IPEX syndrome.

Thyroid-stimulating hormone (TSH), FT4, and thyroid antibodies are used to evaluate for autoimmune thyroid disease.

Serum glucose test, oral glucose tolerance test, and anti-islet cell antibodies testing are used to assess insulin-dependent diabetes. Anti–glutamic acid decarboxylase (GAD) antibodies and anti-insulin antibodies have also been reported in patients with IPEX syndrome. [7]

CBC count with differential is used to evaluate for autoimmune hemolytic anemia, thrombocytopenia, and/or neutropenia. Marked eosinophilia has been described. If anemia is present, evaluation for autoantibody production with Coombs testing may be performed. Patients with IPEX syndrome usually have intermittent eosinophilia. [12, 24]

BUN and creatinine level measurement and urinalysis with microscopy is used to assess evidence of autoimmune renal disease.

Liver function tests assess for evidence of autoimmune liver disease.

Serum immunoglobulin E (IgE) and immunoglobulin A (IgA) levels are usually elevated in patients with IPEX syndrome. [12]

Flow cytometry of peripheral blood CD4+ CD25+ FOXP3+ usually reveals decreased T cells in patients with IPEX syndrome. [25]

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Imaging Studies

Imaging studies are not routinely required for the diagnosis and management of IPEX syndrome.

Consider targeting imaging studies to evaluate for sinus disease and potential bronchiectasis.

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Other Tests

Quantitative immunoglobulins (immunoglobulin G [IgG], immunoglobulin M [IgM], immunoglobulin A [IgA]), antibody response to protein and polysaccharide antigens, and B-cell subsets are normal. Low immunoglobulin levels in a patient with IPEX syndrome is suggestive of a significant protein-losing enteropathy. [12]

T-cell subsets, in vitro lymphocyte proliferative response to mitogens, and delayed-type hypersensitivity are normal. Increased TH-2 cytokine (interleukin [IL]-4, IL-5, IL-13) and decreased TH-1 cytokine (interferon [INF]-γ) expression has been reported in patients with IPEX syndrome. [14]

Although autoimmune neutropenia is commonly found in IPEX syndrome, neutrophil function is preserved.

Patients with IPEX syndrome have normal serum complement levels. [12]

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Procedures

Endoscopy (upper and lower) with biopsy is used to evaluate for enteropathy. Skin biopsy is used to characterize dermatitis.

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Histologic Findings

All 3 of the histologic findings below are associated with various degrees of villous atrophy and cellular inflammatory infiltrate. [13]

Enteropathy with complete depletion of goblet cells was also associated with IPEX syndrome. [13]

Lymphocytic infiltrate with destruction of exocrine tissue and loss of islet cells is observed. [12]

Dermatologic findings include the following: [26]

  • Eczematous dermatitis

  • Psoriaform lesions

  • Lymphocytic dermal infiltrate

Thyroid findings include the following:

  • Lymphocytic infiltrate [12]

  • Thymus

  • Depletion of lymphocytes and Hassall corpuscles with cellular atrophy or dysplasia [12]

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Staging

See the list below:

  • No current staging classification has been established for IPEX syndrome. However, emerging research may provide a basis for development of a staging system. [27]

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