Duodenal lymphocytosis, sometimes called lymphocytic duodenitis, lymphocytic duodenosis, or duodenal intraepithelial lymphocytosis, is a condition where an increased number of intra-epithelial

lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...

is seen in biopsies of the

duodenal The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

when these are examined microscopically. This form of

lymphocytosis Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the cond ...

is often a feature of

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

but may be found in other disorders.

Presentation

The condition is characterised by an increased proportion of lymphocytes in the

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

of the duodenum, usually when this is greater than 20–25 per 100

enterocytes Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its s ...

. Intra-epithelial lymphocyte (IEL) are normally present in intestine and numbers are normally greater in the

crypts A crypt (from Latin '' crypta'' "vault") is a stone chamber beneath the floor of a church or other building. It typically contains coffins, sarcophagi, or religious relics. Originally, crypts were typically found below the main apse of a chu ...

and in the

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previous ...

; these are distinct from those found in the

lamina propria The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenita ...

of the intestinal mucosa. IELs are mostly

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s. 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%.

Causes

The list of possible causes is wide, including coeliac disease,

environmental enteropathy Environmental enteropathy (EE or tropical enteropathy or environmental enteric dysfunction) is a disorder of chronic intestinal inflammation. EE is most common amongst children living in low-resource settings. Acute symptoms are typically minimal ...

(

tropical sprue Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a mor ...

), autoimmune enteropathy,

small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is r ...

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

damage, ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is though ...

'', other infections and

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

Diagnosis

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

villous Villus ( la, "shaggy hair", plural villi) may refer to: * Intestinal villus, refers to any one of the small, finger-shaped outgrowths of the epithelial lining of the wall of the intestine. Clusters of projections are referred as intestinal villi. ...

architecture. In

(also known as

gluten-sensitive enteropathy Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

), 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 A crypt (from Latin ''crypta'' "vault") is a stone chamber beneath the floor of a church or other building. It typically contains coffins, sarcophagi, or religious relics. Originally, crypts were typically found below the main apse of a chur ...

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...

are the other findings in other Marsh stages of coeliac disease. Antibodies associated with coeliac disease were reported in around 11% of cases. These IgA endomysial antibodies and

anti-transglutaminase antibodies Anti-transglutaminase antibodies (ATA) are autoantibodies against the transglutaminase protein. Antibodies serve an important role in the immune system by detecting cells and substances that the rest of the immune system then eliminates. These cel ...

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-DQ HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromos ...

2 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 An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...

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 Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by ''Cryptosporidium'', a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in ...

and

Giardiasis Giardiasis is a parasitic disease caused by ''Giardia duodenalis'' (also known as ''G. lamblia'' and ''G. intestinalis''). Infected individuals who experience symptoms (about 10% have no symptoms) may have diarrhea, abdominal pain, and weight los ...

can also be associated with an increase in IELs.

Management

The management is that of any identified associated disorder such as a

gluten free diet A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats. The inclu ...

for cases with coeliac disease or treatment of associated infections.

Prognosis

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 Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grain ...

-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.

References

{{reflist, 2 Gastrointestinal tract disorders Inflammations Pathology