Five criteria for diagnosing autoimmune enteropathy are now available thanks to a compilation of 15 patients at the Mayo Clinic, which has more than doubled the number of cases in the published literature.
The researchers found that only about half of the patients had histology results that fit the typical pattern previously reported, but 80% had a predisposition to autoimmune disease, as indicated by their history or levels of circulating antibodies.
Based on the cohort, the investigators also proposed criteria that could be used for definitive diagnosis.
The first reported case of autoimmune enteropathy was that of a child in 1982, said Dr. Salma Akram, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn. More recently, a total of 11 adult-onset cases have been reported in the literature.
The Mayo cases were all patients who had protracted diarrhea leading to weight loss and malnutrition. In 13 of the 15 cases, the patients' physicians ruled out celiac disease because the patient did not respond to a gluten-free diet and did not have an HLA genotype indicative of celiac disease susceptibility.
The other two cases fulfilled diagnostic criteria for refractory sprue. However, those 2 patients were among the 13 who tested positive for antienterocyte and/or antigoblet cell antibodies; a total of 14 of the 15 patients received such testing.
The median length of time between the onset of symptoms and diagnosis was 1.5 years. Abdominal CT was unremarkable in the cohort, except for a finding of prominent mesenteric lymph nodes in six of the patients.
Dr. Akram and colleagues found that only eight patients had small-bowel biopsy histology with the features that are considered characteristic of autoimmune enteropathy—features such as minimal intraepithelial lymphocytes and dense lamina propria inflammation.
The other seven individuals had spruelike histology, and it may be that the two conditions can coexist, the investigators suggested. This theory was bolstered by the finding that five of the seven patients had elevated IgA tissue transglutaminase antibodies.
Based on the Mayo cohort, the authors suggested that the following five criteria should be considered for establishing the diagnosis of adult autoimmune enteropathy, with the first four criteria being absolutely necessary for reaching a definitive diagnosis:
▸ Adult-onset chronic diarrhea lasting longer than 6 weeks in duration.
▸ Malabsorption.
▸ Specific small-bowel histology of partial/complete villous blunting, deep crypt lymphocytosis, increased crypt apoptotic bodies, and minimal intraepithelial lymphocytosis.
▸ Exclusion of other causes of villous atrophy, including celiac disease, refractory sprue, and intestinal lymphoma.
▸ Antienterocyte and/or antigoblet cell antibodies.
Treatments for autoimmune enteropathy that have been reported in the past have included corticosteroids, cyclophosphamide, tacrolimus, and infliximab.
Most of the Mayo Clinic patients (14 of 15) were treated with immunosuppressive therapy. Four received prednisone alone, and most of the others received prednisone followed by budesonide, azathioprine, and/or 6-mercaptopurine.
Two patients received treatment with prednisone followed by either 6-mercaptopurine or azathioprine with infliximab. One patient received metronidazole for 4 weeks as well as diphenoxylate, but did not respond. Nine of the patients responded to their treatment with complete resolution of their diarrhea, and three patients had a partial response.
High-dose steroids (greater than 40 mg/day) produced a rapid clinical response in two patients, but both needed additional therapy to maintain remission within 3–11 months.
One patient responded to prednisone 10 mg/day, and remained in remission on 5 mg/day for 14 months. Five of the responders went into remission with prednisone at doses of 20–60 mg/day in 4–8 weeks, then were maintained with budesonide. Infliximab was used in two patients and produced a rapid response, the investigators said.