Duodenal lymphocytosis

The condition is characterised by an increased proportion of lymphocytes in the epithelium of the duodenum, usually when this is greater than 20-25 per 100 enterocytes.[1] Intra-epithelial lymphocyte (IEL) are normally present in intestine and numbers are normally greater in the crypts and in the jejunum; these are distinct from those found in the lamina propria of the intestinal mucosa. IELs are mostly T cells.[1] Increased numbers of IELs are reported in around 3% of in duodenal biopsies, depending on case mix, but may be increasingly being found, in up to 7%.[2][3]

The list of possible causes is wide, including coeliac disease, environmental enteropathy (tropical sprue), autoimmune enteropathy, small intestinal bacterial overgrowth, NSAID damage, Helicobacter pylori, other infections and Crohn's disease.[1]

Diagnosis is made by accurate counting of intraepithelial lymphocytes during histological examination of the duodenum.[1] The definition of the condition includes the requirement that the duodenal histological appearances are otherwise unremarkable, specifically with normal villous architecture.[2]

In coeliac disease (also known as gluten-sensitive enteropathy), duodenal lymphocytosis is found in untreated or partially treated cases. This is the least severe type of change, known as the Marsh I stage, in the classification of histological changes in coeliac disease. Additional features including villous atrophy and crypt hyperplasia are the other findings in other Marsh stages of coeliac disease.[4][1]

Antibodies associated with coeliac disease were reported in around 11% of cases.[1] These IgA endomysial antibodies and anti-transglutaminase antibodies are very sensitive and specific for coeliac disease implying that this proportion of duodenal lymphocytosis cases has definite coeliac disease. Around 33% of cases have the HLA-DQ2 allele, which is found in over 90% of people with coeliac disease. Absence of HLA-DQ2 (and the rarer HLA-DQ8) makes coeliac disease most unlikely.[5] As antibody-negative coeliac disease is recognised, HLA status, persistence or progression of the duodenal IEL numbers following a gluten challenge, followed by symptomatic improvement on a gluten-free diet, has been used to be more certain about the diagnosis, which was made in 22% of one series of over 200 adult cases. [5]

Helicobacter infection is a common finding at endoscopy and although duodenal IEL counts were found to be slightly higher with this infection, this was not considered to be a meaningful cause in children.[6] Other infections, including Cryptosporidiosis and Giardiasis can also be associated with an increase in IELs.[2]

The management is that of any identified associated disorder such as a gluten free diet for cases with coeliac disease[5] or treatment of associated infections.[2]

When duodenal lymphocytosis is associated with other features of coeliac disease, in particular positive antibodies, or HLA-DQ2/8 and a family history, treatment with a gluten-free diet produces an improvement in IEL numbers.[5] Diarrhoea, thyroiditis, weakness and folate deficiency were other predictors of the development of gluten sensitivity and coeliac disease, which developed in 23 of 85 patients over 2 years in one series.[7]