Introduction: Ongoing symptoms as well as villous atrophy are required for a diagnosis of ‘refractory’ coeliac disease (RCD), differentiated as type 1 or type 2 based on the presence of an abnormal population of cytoplasmic CD3+, surface CD3- lymphocytes in the intestinal epithelium (IELs). Just as patients with (responsive) coeliac disease and villous atrophy may be asymptomatic, patients with persistent duodenal inflammation may also lack symptoms – ‘histologically refractory type 1’ coeliac disease1. Such patients may be detected by routine re-biopsy on a gluten free diet, as has been a part of our coeliac pathway since 2003.
Method and patients: Patients with a diagnosis of coeliac disease with ongoing villous atrophy despite strict dietary adherence but without symptoms and not receiving immunomodulatory therapy were followed up by annual surveillance duodenal biopsies between 2015 and 2025. All underwent IEL flow cytometry on at least one occasion.
Results: n=15 (11 females (av age 65 yrs), 4 males (av age 63 yrs)). Average follow up was 5.5 yrs (2-11); average of 3.5 gastroscopies (2-8). Average time since diagnosis was 16.7 yrs (2-38). 12 DQ2 +, 2 DQ8+. Sub-total villous atrophy was persistent in 13, partial villous atrophy in 2 patients. Three patients had microscopic colitis. Two showed cavitating mesenteric lymph nodes. One male progressed to RCD2 on flow cytometry after 3 years at the age of 76 years. Resolution of changes was seen in three patients after 4, 7 and 8 years.
Discussion: ‘Asymptomatic’ RCD1 may remain stable for years, resolve after time or progress to RCD2. We initially demonstrated progression from RCD1 to RCD2 retrospectively by dual immunohistochemistry in 20102. Here we demonstrate progression to RCD2 prospectively by flow cytometry for the first time. Patients with asymptomatic RCD1 are at risk and should be identified and followed up.