IPEX Syndrome (Immune Dysregulation, Polyendocrinopathy, Autoimmune Enteropathy, X-linked)
Definition
- Hereditary autoimmune enteritis with associated autoimmune disorders due to mutation in FOXP3 gene
See also for non-X linked form of disease:
Diagnostic Criteria
- Autoimmune enteropathy associated with any of several autoimmune disorders and mutation in FOXP3 gene
- A wide variety of organ systems may be involved with variability between patients
- Autoimmune enteropathy usually presents in first six months of life
- Principally involves small intestine
- May also involve stomach and large intestine
- Nearly all show partial or complete villous atrophy
- Nearly all show an increase in lamina propria lymphocytes
- Infiltrate predominantly composed of CD3+ CD4+ alpha beta T cells
- Mild to marked increase in intra-epithelial lymphocytes
- Variable reports in the literature
- Infiltrate predominantly composed of CD3+ CD4+ alpha beta T cells
- Inconspicuous to prominent apoptosis in crypts
- Crypts may be hyperplastic or destroyed
- Goblet cells may be absent
- Anti-enterocyte brush border antibodies demonstrable by indirect immunofluorescence
- Anti-goblet cell antibodies may be present but less specific
- Polyendocrinopathy - frequently multiple systems involved
- Most frequent is insulin dependent diabetes mellitus
- Due to autoimmune destruction of islets
- Thyroiditis, adrenal insufficiency
- Immune dysregulation frequently occurs in addition to the above
- Coombs positive hemolytic anemia
- Autoimmune thrombocytopenia
- Neutropenia
- Interstitial nephropathy and/or glomerulonephritis
- Eczema
- Elevated IgE
- X-linked heredity
- Mutations in FOXP3 gene (Xp11.23) identifiable by sequencing
- Rare cases have the same constellation of findings but are not X-linked
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/updates : 11/20/11
