Duodenal lymphocytosis, sometimes called lymphocytic duodenitis, lymphocytic duodenosis, or duodenal intraepithelial lymphocytosis, is a condition where an increased number of intra-epithelial lymphocytes is seen in biopsies of the duodenal mucosa when these are examined microscopically. It is often a feature of coeliac disease but may be found in other disorders.
The condition is diagnosed when the proportion of lymphocytes in the epithelium of the duodenum is greater than 20-25 per 100 enterocytes. Intra-epithelial lymphocyte (IEL) 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 which recognise antigens and regulate the immune response.
The definition of the condition includes the requirement that the duodenal histological appearances are otherwise unremarkable, specifically with normal villous architecture. 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.
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%. The differential diagnosis of possible causes is wide, especially suggesting coeliac disease, but also includes environmental enteropathy (tropical sprue), autoimmune enteropathy, small intestinal bacterial overgrowth, NSAID damage, Helicobacter pylori and other infections and Crohn's disease.
Antibodies associated with coeliac disease were reported in around 11% of cases. 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. 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. 
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. Other infections, including Cryptosporidiosis and Giardiasis can also be associated with an increase in IELs.
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. 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.
- Lauwers GY, Fasano A, Brown IS (2015). "Duodenal lymphocytosis with no or minimal enteropathy: much ado about nothing?". Mod. Pathol. 28 Suppl 1: S22–9. doi:10.1038/modpathol.2014.135. PMID 25560597.
- Hammer ST, Greenson JK (2013). "The clinical significance of duodenal lymphocytosis with normal villus architecture". Arch. Pathol. Lab. Med. 137 (9): 1216–9. doi:10.5858/arpa.2013-0261-RA. PMID 23991733.
- Marsh MN (1992). "Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue')". Gastroenterology. 102 (1): 330–54. doi:10.1016/0016-5085(92)91819-p. PMID 1727768.
- Shmidt E, Smyrk TC, Boswell CL, Enders FT, Oxentenko AS (2014). "Increasing duodenal intraepithelial lymphocytosis found at upper endoscopy: time trends and associations". Gastrointest. Endosc. 80 (1): 105–11. doi:10.1016/j.gie.2014.01.008. PMID 24565068.
- Aziz I, Key T, Goodwin JG, Sanders DS (2015). "Predictors for Celiac Disease in Adult Cases of Duodenal Intraepithelial Lymphocytosis". J. Clin. Gastroenterol. 49 (6): 477–82. doi:10.1097/MCG.0000000000000184. PMID 25014240.
- Guz-Mark A, Zevit N, Morgenstern S, Shamir R (2014). "Duodenal intraepithelial lymphocytosis is common in children without coeliac disease, and is not meaningfully influenced by Helicobacter pylori infection". Aliment. Pharmacol. Ther. 39 (11): 1314–20. doi:10.1111/apt.12739. PMID 24702235.
- Losurdo G, Piscitelli D, Giangaspero A, Principi M, Buffelli F, Giorgio F, Montenegro L, Sorrentino C, Amoruso A, Ierardi E, Di Leo A (2015). "Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up". World J. Gastroenterol. 21 (24): 7545–52. doi:10.3748/wjg.v21.i24.7545. PMC . PMID 26140001.