The Other Causes of Severe Enteropathy with Villous Atrophy Non-Responsive to a Gluten-Free Diet

The first step in approaching someone with refractory celiac disease is to confirm the original diagnosis of celiac disease. This involves reviewing haplotype testing, prior serologies, histology, family history, and the response both clinically and histologically to a gluten-free diet. If the original diagnosis is called into question, alternative causes of severe enteropathy with villous atrophy need to be considered. In this chapter we will focus on these alternative causes, and particularly focus on those that lead to clinical symptoms and signs of malabsorption and diarrhea, in addition to villous atrophy. For this reason, we will not review causes of villous atrophy with no accompanying malabsorption, such as peptic duodenitis. We will also not review very uncommon causes such as macroglobulinemia, lipid storage disorders, diffuse signet cell carcinoma, tuberculosis, lymphangiectasia, abetalipoproteinemia, and amyloidosis. Crohn’s disease is another potential cause of villous atrophy that will not be discussed.