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

  • Author: Satyen M Gada, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Mar 25, 2014
 

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.[17, 18] 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.[19]

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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Contributor Information and Disclosures
Author

Satyen M Gada, MD Assistant Professor, Department of Pediatrics and Medicine, Uniformed Services University of the Health Sciences; Staff, Department of Allergy and Immunology, Walter Reed Army Medical Center, Bethesda, MD

Satyen M Gada, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Coauthor(s)

Cecilia P Mikita, MD, MPH Associate Program Director, Allergy-Immunology Fellowship, Associate Professor of Pediatrics and Medicine, Uniformed Services University of the Health Sciences; Staff Allergist/Immunologist, Walter Reed National Military Medical Center

Cecilia P Mikita, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Taylor Banks, MD Chief, Allergy/Immunology Clinic, Walter Reed National Military Medical Center; Assistant Professor of Pediatrics, Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Associate Program Director, NCC Allergy-Immunology Fellowship Program and NCC Transitional Year Internship Program

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

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.

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

C Lucy Park, MD Chief, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago College of Medicine

C Lucy Park, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, Chicago Medical Society, American Medical Association, Clinical Immunology Society, Illinois State Medical Society

Disclosure: Nothing to disclose.

References
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