Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital

Table 1 Different criteria proposed for diagnosing autoimmune enteropathy

Unsworth and Walker-Smith[9] proposed in 1985	Akram et al[8], proposed in 2007	Sharma et al[7], proposed in 2018	Schiepatti et al[6], proposed in 2022
(1) Protracted diarrhea and severe enteropathy; (2) No response to exclusion diet or total parenteral nutrition; (3) Evidence of predisposition to autoimmune disease (presence of circulating autoantibodies and/or associated disease also thought to be autoimmune); and (4) No severe immunodeficiency	(1) Adult-onset chronic diarrhea (> 6 wk’ duration); (2) Malabsorption; (3) Specific small bowel histology, partial/complete villous blunting, deep crypt lymphocytosis, increased crypt apoptotic bodies, minimal intraepithelial lymphocytosis (IEL means > 40 per 100 epithelial cells); (4) Exclusion of other causes of villous atrophy including celiac disease, refractory sprue, and intestinal lymphoma; and (5) Anti-enterocyte (AE) and/or anti–goblet cell (AG) antibodies. Criteria 1-4 are required for a definite diagnosis of AIE. Presence of AE and/or AG antibodies is an important diagnostic support, but their absence does not exclude the diagnosis of AIE	(1) Adult-onset protracted diarrhea (> 6 wk) not responsive to any dietary exclusion; (2) Associated with specific small-bowel histology, villous atrophy, minimal IEL, increased crypt apoptotic bodies, absence of goblet or Paneth cells; and (3) Systematic exclusion of other causes of villous atrophy including CD or RCD (based on combination of celiac serology, HLA typing, histopathology features, and response to GFD), drug-induced enteropathy (based on history of starting medication and its correlation with symptoms, duration of treatment, histopathology and effect after discontinuation), common variable immunodeficiency-associated enteropathy (based on total immunoglobulin titers and histopathology [presence of plasma cells, lymphoid aggregates]), collagenous sprue and colitis (based on histopathology), and intestinal lymphoma	The following criteria must be satisfied for the diagnosis: (1) Severe malabsorption symptoms (chronic diarrhea, weight loss, nutritional deficiencies and electrolyte imbalance) unresponsive to any dietary restriction; (2) Frank villous atrophy unresponsive to any dietary restriction; (3) IgA/IgG positive enterocyte antibodies (indirect immunofluorescence on human/monkey jejunum); (4) Negative celiac serology; and (5) Exclusion of other causes of villous atrophy
			The following criteria were considered supportive for the diagnosis: (1) History of associated autoimmune conditions; (2) Clinical response to immunosuppressive treatments; (3) Deep crypt lymphocytosis and/or plasma cells infiltration, neutrophilic cryptitis ± crypt microabscesses and lack/decrease of Paneth cells on duodenal histology; (4) Positive serum anti-AIE 75 KD antibodies (ELISA) or nonorgan specific autoantibodies; and (5) Absence of severe immunodeficiencies, diagnostic role of serum antigoblet cells antibodies, involvement of other sites of the GI tract and some duodenal histopathological features (include intraepithelial lymphocytes count, crypt hyperplasia and crypt apoptotic bodies, lack of gamma-delta T cells and depletion of goblet cells)

IEL: Intraepithelial lymphocyte; CD: Celiac disease; RCD: Refractory celiac disease; HLA: Human leukocyte antigen; GFD: Gluten-free diet; ELISA: Enzyme-linked immuno sorbent assay.