Adult-Onset Autoimmune Enteropathy in an European Tertiary Referral Center

Abstract

INTRODUCTION: Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center. METHODS: Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10). RESULTS: Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23–73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation. DISCUSSION: Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients.

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

“…According to the diagnostic criteria of 2022, antibodies against enterocytes are defined as the essential diagnostic criterion (Table 1 ), which still lacks validation. Due to the inconvenience of testing, only a small number of patients in our cohort tested for AE or AG antibodies, and all negative (0%), lower than the detection rates in other cohorts, with 52%-77% for AE[ 7 , 34 ] and 7% for AG[ 7 ]. It remains unclear whether AE and AG contribute pathogenically to the development of AIE, and some believe that these antibodies are only byproducts secondary to mucosal injury.…”

“…It remains unclear whether AE and AG contribute pathogenically to the development of AIE, and some believe that these antibodies are only byproducts secondary to mucosal injury. AEs can also be found in CD patients (4/52, 7.7%), refractory CD type 2 patients (3/18, 16.7%), and enteropathy-associated T-cell lymphoma patients (2/10, 20%)[ 34 ], and AG can be found in CD patients (up to 28%)[ 3 ]. In general, autoantibodies, especially AG, are supportive but cannot lead to a definite diagnosis of AIE[ 35 ].…”

“…However, how to predict and control diarrhea relapse with these medications remains challenging. Several studies have reported other unusual or unconventional treatment options for AIE[ 23 , 34 , 36 - 39 ]. Some patients died because of various causes, such as myocardial infarction[ 2 ], candidiasis and sepsis secondary to immunosuppression[ 11 ], and multiorgan dysfunction syndrome[ 40 ].…”

Beyond IBD: the genetics of other early-onset diarrhoeal disorders

“…Autoimmune enteropathy (AIE) is an immune-mediated multifaceted disorder presenting with intractable diarrhoea predominantly in early childhood (Ahmed et al 2019 ). Although initially thought to be a disease of childhood, an increasing number of adult onset cases have been reported (Akram et al 2007 ; van Wanrooij et al 2021 ). Unsworth and Walker-Smith proposed the initial diagnostic criteria in 1985 which included severe diarrhoea unresponsive to dietary changes, evidence of autoimmunity in the absence of a known immunodeficiency (Unsworth and Walker-Smith 1985 ).…”

Adult-Onset Autoimmune Enteropathy: A Case Report

“…Later recognised in adults [ 2 ], the first proposed diagnostic criteria were severe diarrhoea, small villous atrophy, no response to any dietary restrictions (especially gluten), anti-enterocyte antibodies, and/or a predisposition to autoimmunity and absence of immunodeficiency, e.g., hypogammaglobulinemia or common variable immunodeficiency disorder (CVID) [ 3 ]. Refined criteria have been proposed, implying characteristic histological findings (villous blunting, deep crypt lymphocytosis, abnormal apoptosis, and minimal intraepithelial lymphocytosis) and the absence of other causes for villous atrophy as additional major criteria for the diagnosis, while gut-specific antibodies are no longer required for the diagnosis [ 4 , 5 ]. Medications (olmesartan, non-steroidal anti-inflammatory drugs (NSAIDs), immune checkpoint blockade therapy, particularly CTLA-4 antibodies) have since been shown to give rise to a secondary form of AIE [ 6 ].…”