Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX) Clinical Presentation

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

History

Immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome should be considered in young male patients with intractable diarrhea with accompanying villous atrophy or failure to thrive. Further support for the diagnosis is gained by the presence of the other 2 elements of the predominant triad: eczematous or psoriasiform dermatitis and early onset, insulin-dependent diabetes. [5, 12]

Failure to thrive, growth retardation, and/or cachexia in the setting of watery, secretory diarrhea are common historical elements. The diarrhea is occasionally present prior to feeding but generally appears or worsens after feeds. Enteric rest and gluten-free diet do little to alter the course of the enteropathy. [3]

Glucose intolerance can present at birth, but generally the patients manifest symptoms after 3-4 months of life. Anti-islet cell antibodies have been found in some patients. [5]

Thyroid disease, both hyperthyroidism and hypothyroidism, has been noted in as many as 30% of patients; hypothyroidism is more common. [12]

The forms of dermatitis vary, with many patients presenting with an eczematous rash; however, a diffuse erythematous rash, psoriasiform rashes, pemphigoid nodularis, and, rarely, alopecia universalis have been noted. [5, 14]

One third of patients develop renal disease, with proteinuria and hematuria representing the most common presenting symptoms. [5]

A history of thrombocytopenia or Coombs test–positive anemia may also be present. [2]

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Physical

Patients’ general appearance, growth, and development are important to note. Cachexia, small size, and poor weight gain related to failure to thrive are often present. [3]

Skin examination can detect the several possible forms of dermatitis, including eczematous, psoriasiform, and a more generalized erythematous rash and, rarely, alopecia universalis. [5, 14]

A joint examination may reveal signs of arthritis, such as edema, erythema, and limitation of range of motion, but joint involvement is not common. [12]

Lymphadenopathy and splenomegaly are variably present. [2]

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Causes

The FOXP3 gene at Xp11.23-Xq13.3 is the causative gene for IPEX syndrome. This gene is critical for the development of CD4+ CD25+ regulatory T cells (Treg). The absence of these cells has been linked to autoimmune disease and other forms of immune dysregulation.

Of patients with IPEX syndrome, 60% have identifiable mutations in the FOXP3 gene. Some patients with IPEX-like conditions may have mutations involving the regulatory sequences in the FOXP3 gene. [18, 19] A growing understanding of related, IPEX-like conditions now includes mutations in CD25, STAT5b, and ITCH syndrome. These conditions also impact Treg cells or signaling pathways in which FOXP3 also participates. [20]

It is an X-linked recessive disease process, and a male child of a female carrier has a 50% chance of being affected. A female child has a 50% probability of being an asymptomatic carrier.

The phenotypic manifestations of this disease vary, and their relationship to the monogenic origin is unclear.

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Complications

Complications include the following:

  • Infection

  • Malnutrition

  • Complications of the associated endocrine abnormalities

  • Complications of the associated hematologic abnormalities

  • Complications of hematopoietic stem cell transplantation (HSCT)

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