Small intestine & ampulla
Inflammatory disorders
Autoimmune enteropathy

Editorial Board Member: Catherine E. Hagen, M.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Archana Shenoy, M.D.
Pierre A. Russo, M.D.

Topic Completed: 5 November 2020

Minor changes: 5 November 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Autoimmune enteropathy small intestine

Archana Shenoy, M.D.
Pierre A. Russo, M.D.
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Cite this page: Shenoy A, Russo PA. Autoimmune enteropathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/smallbowelautoimmuneenter.html. Accessed November 23rd, 2020.
Definition / general
  • Immune mediated disorder causing small intestinal atrophy and resulting in severe diarrhea
Essential features
  • Intractable diarrhea leading to malabsorption and electrolyte imbalances
  • Histologic findings include intestinal atrophy with variable inflammation (acute and chronic), crypt apoptosis and absence of goblet / Paneth cells
  • Indirect immunofluorescence on normal intestinal tissue using patient’s serum is useful in detecting circulating anti-enterocyte and antigoblet cell antibodies
  • Extraintestinal autoimmune manifestations are possible
  • Prognosis is much improved with immunomodulatory therapy
Terminology
  • Autoimmune enteropathy
  • Syndromic forms: immune dysregulation, polyendocrinopathy, enteropathy and X linked (IPEX) syndrome; autoimmune polyglandular syndrome (APS 1) also known as autoimmune phenomena, polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome
ICD coding
  • ICD-10: K63.9 - disease of intestine, unspecified
  • ICD-11: 4A01.21 - immune dysregulation syndromes presenting primarily with autoimmunity
Epidemiology
Sites
  • Small intestine, tubular gastrointestinal tract
  • Extraintestinal manifestations: diabetes mellitus, autoimmune hepatitis, alopecia, ectodermal dystrophy, candidiasis, hypothyroidism
Pathophysiology
  • Exact pathogenesis is unclear
  • Intestinal epithelial damage from anti-enterocyte antibodies and antigoblet cell antibodies
Etiology
  • Complex, multifactorial
  • IPEX syndrome: FOXP3 mutation leading to impaired function / number of regulatory T cells, X linked
  • APECED syndrome: AIRE mutation resulting in lack of suppression of autoreactive T cells, autosomal recessive
  • IPEX-like syndrome: mutations in genes related to regulatory T cell functions such as CD25, STAT5b, STAT1, LRBA and CTLA4 (Front Immunol 2018;9:2411)
Clinical features
Diagnosis
  • Combination of clinical presentation, histologic findings and laboratory studies
Laboratory
  • Anti-enterocyte and antigoblet cell antibodies demonstrable by indirect immunofluorescence; predominantly IgG, less commonly IgM and IgA
  • Sequencing for known mutations
Prognostic factors
  • Can be fatal if untreated; advances in treatment and aggressive nutritional care have improved outcomes
Case reports
Treatment
  • Supportive nutrition, enteral and parenteral
  • Immunosuppression (steroids, immunomodulatory chemotherapeutic agents, biologic medications)
  • Stem cell transplant (IPEX syndrome) (Dig Dis Sci 2019;64:643)
Microscopic (histologic) description
  • Villous architectural abnormalities
    • Villous blunting, severe villous atrophy and crypt hyperplasia
  • Absence of an epithelial cell subtype
  • Inflammation:
    • Increased intraepithelial lymphocytes
    • Active (acute) inflammation and cryptitis
  • Increased crypt apoptosis resembling graft versus host disease
  • Findings pronounced in duodenum / small bowel; variable findings can also be seen in the stomach and colon (Am J Surg Pathol 2014;38:1319)
  • Severity of histologic findings variable among individuals and reversible with therapy
Microscopic (histologic) images

Contributed by Archana Shenoy, M.D.
Duodenal biopsy Duodenal biopsy

Duodenal biopsy

Colon biopsy

Colon biopsy

Immunofluorescence description
  • Indirect immunofluorescence test performed using patient’s serum on normal frozen small intestinal tissue can assist in diagnosis; positive staining of apical and basolateral borders of enterocytes or goblet cell staining indicates the presence of anti-enterocyte and antigoblet cell antibodies (Pediatr Dev Pathol 1999;2:65)
Immunofluorescence images

Contributed by Pierre A. Russo, M.D.
Indirect immunofluorescence test

Indirect
immunofluorescence
test

Electron microscopy description
  • Not routinely used for diagnosis; if performed, helpful in eliminating congenital diarrheas that are in the differential diagnoses
Sample pathology report
  • Duodenum, biopsy:
    • Severe villous blunting with absence of goblet cells and Paneth cells, intraepithelial lymphocytosis and increased crypt apoptosis
  • Duodenum, biopsy:
    • Chronic active duodenitis with increased apoptosis (see comment)
    • Comment: The biopsies demonstrate histologic features that raise the possibility of autoimmune enteropathy, in the correct clinical context. If celiac disease is excluded, serologic or molecular testing for autoimmune enteropathy is recommended.
Differential diagnosis
  • Celiac disease:
    • Intact goblet and Paneth cells
    • Typically more pronounced intraepithelial lymphocytes
    • Typically responsive to gluten free diet
    • Positive serologic tests (antiendomysial antibodies and tissue transglutaminase) for celiac disease
  • Very early onset inflammatory bowel disease:
    • Intact goblet and Paneth cells
    • Granulomas (in Crohn’s disease)
  • Infections:
    • Stool polymerase chain reaction tests, cultures
    • Acute onset of symptoms responsive to antibiotic medications
  • Common variable immunodeficiency:
    • Paucity of lamina propria plasma cells
  • Congenital diarrheas:
  • Graft versus host disease
    • History of stem cell transplant
Additional references
Board review style question #1

Which of the following findings when present would distinguish autoimmune enteropathy from celiac disease?

  1. Absence of Paneth cells and goblet cells
  2. Cryptitis
  3. Intraepithelial lymphocytosis
  4. Villous blunting
Board review answer #1
A. Absence of Paneth cells and goblet cells

Comment Here

Reference: Autoimmune enteropathy
Board review style question #2
Mutation in which of the following genes is associated with IPEX syndrome?

  1. FOXO1
  2. FOXP3
  3. SS18
  4. TFE3
Board review answer #2
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