From the Guidelines
Refractory celiac disease (RCD) is defined as persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten-free diet for at least 6-12 months, as stated in the most recent guidelines 1. This condition affects approximately 1% of celiac disease patients who fail to respond to dietary treatment. RCD is classified into two types based on immunophenotypic features:
- Type 1 RCD maintains a normal intraepithelial lymphocyte population with normal expression of surface CD3 and CD8.
- Type 2 RCD is characterized by abnormal intraepithelial lymphocytes lacking surface CD3, CD8, and T-cell receptors while expressing intracellular CD3. Three infectious causes of villous atrophy include:
- Giardia lamblia infection
- Small intestinal bacterial overgrowth (SIBO)
- Cryptosporidium infection Three medications that can cause villous atrophy include:
- Olmesartan (an angiotensin II receptor blocker)
- Mycophenolate mofetil (an immunosuppressant)
- Non-steroidal anti-inflammatory drugs (NSAIDs) Patients with suspected RCD should undergo comprehensive evaluation including repeat duodenal biopsies, HLA typing, serology testing, and flow cytometry to distinguish between the two types, as management approaches differ significantly, as recommended by recent studies 1.
From the Research
Definition of Refractory Celiac Disease
Refractory celiac disease (RCD) is defined by persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 6-12 months in the absence of other causes of non-responsive treated celiac disease and overt malignancy 2, 3, 4, 5, 6.
Types of Refractory Celiac Disease
- Type 1 RCD: characterized by a normal intraepithelial lymphocyte phenotype, and usually improves after treatment with a combination of aggressive nutritional support, adherence to a GFD, and alternative pharmacological therapies 2, 3, 4, 5, 6.
- Type 2 RCD: defined by the presence of abnormal (clonal) intraepithelial lymphocyte phenotype, and has a severe clinical presentation and a very poor prognosis 2, 3, 4, 5, 6.
Infectious Causes of Villous Atrophy
There are no specific infectious causes of villous atrophy mentioned in the provided studies. However, it is mentioned that other causes of chronic small intestinal inflammation and villous atrophy should be excluded in the diagnosis of RCD 2, 3, 4, 5, 6.
Drug Causes of Villous Atrophy
There are no specific drug causes of villous atrophy mentioned in the provided studies. However, it is mentioned that inadvertent intake of gluten should be excluded in the diagnosis of RCD 2, 3, 4, 5, 6.