Duodenal lymphocytosis

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Duodenal lymphocytosis
Other namesLymphocytic duodenitis, Lymphocytic duodenosis, Duodenal intraepithelial lymphocytosis
Specialty Gastroenterology
Causes Coeliac disease, environmental enteropathy and others
Diagnostic method Histological examination of duodenal biopsy
Frequency3–7% of people having duodenal biopsy

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. This form of lymphocytosis is often a feature of coeliac disease but may be found in other disorders.

Contents

Presentation

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]

Causes

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

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]

Management

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]

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-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]

Related Research Articles

<span class="mw-page-title-main">Coeliac disease</span> Autoimmune disorder that results in a reaction to gluten

Coeliac disease or celiac disease 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 barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body, or no obvious symptoms. Coeliac disease was first described in childhood; however, it may develop at any age. It is associated with other autoimmune diseases, such as Type 1 diabetes mellitus and Hashimoto's thyroiditis, among others.

Peptic ulcer disease is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating. With a gastric ulcer, the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of cases.

<i>Helicobacter pylori</i> Species of bacteria

Helicobacter pylori, previously known as Campylobacter pylori, is a gram-negative, flagellated, helical bacterium. Mutants can have a rod or curved rod shape, and are less effective. Its helical body is thought to have evolved in order to penetrate the mucous lining of the stomach, helped by its flagella, and thereby establish infection. The bacterium was first identified as the causal agent of gastric ulcers in 1983 by the Australian doctors Barry Marshall and Robin Warren.

Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier than expected when eating. Indigestion is relatively common, affecting 20% of people at some point during their life, and is frequently caused by gastroesophageal reflux disease (GERD) or gastritis.

<span class="mw-page-title-main">MALT lymphoma</span> Medical condition

MALT lymphoma is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zone of the MALT, and is also called extranodal marginal zone B cell lymphoma.

<span class="mw-page-title-main">HLA-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

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 chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

<span class="mw-page-title-main">Intraepithelial lymphocyte</span>

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).

<span class="mw-page-title-main">Duodenitis</span> Medical condition

Duodenitis is inflammation of the duodenum. It may persist acutely or chronically.

<span class="mw-page-title-main">Gluten-related disorders</span> Set of diseases caused by gluten exposure

Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.

Gluten-sensitive enteropathy–associated conditions are comorbidities or complications of gluten-related gastrointestinal distress. GSE has key symptoms typically restricted to the bowel and associated tissues; however, there are a wide variety of associated conditions. These include bowel disorders, eosinophilic gastroenteritis and increase with coeliac disease (CD) severity. With some early onset and a large percentage of late onset disease, other disorders appear prior to the coeliac diagnosis or allergic-like responses markedly increased in GSE. Many of these disorders persist on a strict gluten-free diet, and are thus independent of coeliac disease after triggering. For example, autoimmune thyroiditis is a common finding with GSE.

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 cells and substances can be foreign and also can be produced by the body. Antibodies against the body's own products are called autoantibodies. Autoantibodies can sometimes errantly be directed against healthy portions of the organism, causing autoimmune diseases.

<span class="mw-page-title-main">HLA-DQ2</span>

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">Enteropathy-associated T-cell lymphoma</span> Complication of coeliac disease

Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.

Oat sensitivity represents a sensitivity to the proteins found in oats, Avena sativa. Sensitivity to oats can manifest as a result of allergy to oat seed storage proteins either inhaled or ingested. A more complex condition affects individuals who have gluten-sensitive enteropathy in which there is an autoimmune response to avenin, the glutinous protein in oats similar to the gluten within wheat. Sensitivity to oat foods can also result from their frequent contamination by wheat, barley, or rye particles.

The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are four types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.

<span class="mw-page-title-main">Dermatitis herpetiformis</span> Chronic autoimmune disorder leading to blistering skin

Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not known. DH is neither related to nor caused by herpes virus; the name means that it is a skin inflammation having an appearance similar to herpes.

HLA A1-B8-DR3-DQ2 haplotype is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is a controversial disorder which can cause both gastrointestinal and other problems.

The gluten challenge test is a medical test in which gluten-containing foods are consumed and (re-)occurrence of symptoms is observed afterwards to determine whether and how much a person reacts to these foods. The test may be performed in people with suspected gluten-related disorders in very specific occasions and under medical supervision, for example in people who had started a gluten-free diet without performing duodenal biopsy.

Ludvig M. Sollid is a Norwegian physician-scientist whose laboratory has made discoveries in the pathogenesis of HLA associated human disorders, most notably celiac disease. He is currently a Professor of Medicine (immunology) at the University of Oslo and a Senior Consultant at Oslo University Hospital.

References

  1. 1 2 3 4 5 6 Lauwers, Gregory Y; Fasano, Alessio; Brown, Ian S (2015). "Duodenal lymphocytosis with no or minimal enteropathy: much ado about nothing?". Modern Pathology. 28 (S1): S22–S29. doi:10.1038/modpathol.2014.135. ISSN   0893-3952. PMID   25560597.
  2. 1 2 3 4 Hammer, Suntrea T. G.; Greenson, Joel K. (2013). "The Clinical Significance of Duodenal Lymphocytosis With Normal Villus Architecture". Archives of Pathology & Laboratory Medicine. 137 (9): 1216–1219. doi:10.5858/arpa.2013-0261-ra. ISSN   0003-9985. PMID   23991733.
  3. ↑ Shmidt, Eugenia; Smyrk, Thomas C.; Boswell, Christopher L.; Enders, Felicity T.; Oxentenko, Amy S. (2014). "Increasing duodenal intraepithelial lymphocytosis found at upper endoscopy: time trends and associations". Gastrointestinal Endoscopy. 80 (1): 105–111. doi:10.1016/j.gie.2014.01.008. ISSN   0016-5107. PMID   24565068.
  4. ↑ Marsh, Michael N. (1992). "Gluten, major histocompatibility complex, and the small intestine". Gastroenterology. 102 (1): 330–354. doi: 10.1016/0016-5085(92)91819-p . ISSN   0016-5085. PMID   1727768.
  5. 1 2 3 4 Aziz, Imran; Key, Tim; Goodwin, John G.; Sanders, David S. (2014). "Predictors for Celiac Disease in Adult Cases of Duodenal Intraepithelial Lymphocytosis". Journal of Clinical Gastroenterology. 49 (6): 477–82. doi:10.1097/mcg.0000000000000184. ISSN   0192-0790. PMID   25014240. S2CID   13090956.
  6. ↑ Guz-Mark, A.; Zevit, N.; Morgenstern, S.; Shamir, R. (2014-04-07). "Duodenal intraepithelial lymphocytosis is common in children without coeliac disease, and is not meaningfully influenced by Helicobacter pylori infection". Alimentary Pharmacology & Therapeutics. 39 (11): 1314–1320. doi: 10.1111/apt.12739 . ISSN   0269-2813. PMID   24702235. S2CID   22316105.
  7. ↑ Losurdo, Giuseppe; Piscitelli, Domenico; Giangaspero, Antonio; Principi, Mariabeatrice; Buffelli, Francesca; Giorgio, Floriana; Montenegro, Lucia; Sorrentino, Claudia; Amoruso, Annacinzia; Ierardi, Enzo; Leo, Alfredo Di (2015-06-28). "Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up". World Journal of Gastroenterology. 21 (24): 7545–52. doi: 10.3748/wjg.v21.i24.7545 . PMC   4481450 . PMID   26140001.
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