Lymphoma, Enteropathy-Associated T-Cell (EATL) 

What Is Enteropathy-Associated T-Cell Lymphoma?

[dropcap]E[/dropcap]nteropathy associated T-cell lymphoma (EATL), although rare, is a tumor of intraepithelial lymphocytes. It is the most common primary gastrointestinal T-cell lymphoma and is characterized by its aggressive course and poor prognosis.

Primary means this malignancy starts out in the intestinal wall rather than spreading to it from a tumor somewhere else in the  body.

EATL usually affects the jejunum and grossly (visible to the eye) appears as multiple ulcers causing circumferential thickening of affected bowel wall without the formation of definite tumor masses most commonly in the proximal small bowel. As such, patients may present with intestinal perforation, obstruction or hemorrhage.¹

Mesenteric lymph nodes in the abdomen are commonly involved.²

Q: How is EATL diagnosed?

A: Work-up of EATL must include immunohistology, T-cell flow cytometry, T-cell rearrangement and adequate imaging with CT and PET scanning.³

Management of EATL requires a combination of early diagnosis and treatment by surgical resection followed by chemotherapy to achieve treatment success. Overall however, the treatment completion rate remains at 50% and EATL carries a poor prognosis with a 5-year survival rate of <20%.⁴

What Is Enteropathy-Associated T-Cell Lymphoma In Celiac Disease and/or Gluten Sensitivity?

• Relationship between enteropathy-associated T cell lymphoma and celiac disease. Enteropathy-associated T cell lymphoma (EATL) is a severe complication of celiac disease. This is a clinically aggressive tumor that arises from the intraepithelial T-cell population increased in celiac disease.⁵,⁶

• Relationship between enteropathy-associated T cell lymphoma and type. EATL is a rare form of high grade T-cell non-Hodgkins lymphoma of the upper small intestine, specifically associated with celiac disease.⁷ EATL is often disseminated (spread widely) at diagnosis. EATLs can occur in 20% of patients as T-cell lymphomas outside of the small bowel such as panniculitis-like lymphoma.
• Relationship between enteropathy-associated T cell lymphoma and presentation. EATL can present in patients with undiagnosed silent celiac disease with usual symptoms of abdominal pain, diarrhea, malnutrition, and weight loss,⁸ or without the usual symptoms.⁹
• Relationship between enteropathy-associated T cell lymphoma and complications. EATL is often multifocal (more than one area affected) with ulcerative lesions, which explains the high perforation rate at presentation or during chemotherapy.¹⁰,¹¹
• Relationship between enteropathy-associated T cell lymphoma and development. Molecular, biological and immunohistochemical studies have shown that the intestinal mucosa distant from the tumor contains clonal populations of small T cells, often of the same clone as the high grade T-cell lymphoma. These findings suggest that EATL arises in the setting of celiac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high grade tumor, which is usually the cause of the presenting symptoms that bring the patient to the doctor.
• Relationship between enteropathy-associated T cell lymphoma and chronic ulcerative enteropathy. Most cases of chronic ulcerative enteropathy are probably part of the same disease. Patients have the celiac associated HLA DQA1*0501, DQB1*0201 phenotype.⁷ 
• Relationship between enteropathy-associated T cell lymphoma and persistent villous atrophy. A Swedish nationwide study investigating the association between mucosal healing in celiac disease and subsequent lymphoma found that  the risk for T-cell lymphoma was higher than that in the general population and was greater among patients with persistent villous atrophy than among those with mucosal healing. Among 7625 patients with celiac disease and follow-up biopsy, 3308 (43%) had persistent villous atrophy.¹²
• Relationship between enteropathy-associated T cell lymphoma and chorea. Chorea has been described as a paraneoplastic phenomenon in patients with non-Hodgkin’s lymphoma and has been described as associated with lymphoma arising from a background of refractory celiac disease. The finding of chorea in association with celiac disease should prompt a search for possible underlying intestinal T-cell lymphoma.¹³

How Prevalent is Enteropathy-Associated T Cell Lymphoma In Celiac Disease and/or Gluten Sensitivity?

Enteropathy-associated T cell lymphoma is the most common neoplasm in celiac disease,¹⁴  and the risk of EATL is markedly increased in celiac disease.¹⁵

What Are The Symptoms Of Enteropathy-Associated T Cell Lymphoma?

Enteropathy-associated T cell lymphoma is marked by these symptoms:

• Abdominal pain that becomes unbearable without narcotics.
• Diarrhea is common.
• Loss of appetite.
• Weight loss is a common symptom, but not always especially when celiac disease is not yet diagnosed.⁹
• Some patients may manifest with nonspecific symptoms for a period of years or an acute emergency of perforation, obstruction, or hemorrhage.¹⁶
• Complications are bowel hemorrhage, obstruction, and perforation.

How Does Enteropathy-Associated T Cell Lymphoma Develop In Celiac Disease and/or Gluten Sensitivity?

• EATL arises from malignant transformation of intra-epithelial T lymphocytes (IEL) due to chronic gluten exposure in celiac disease.¹
• Refractory celiac disease with abberant T cells carries a high risk of development of EATLs.¹⁷
• Multiple nutrient deficiencies may predispose which include omega-3 fatty acids, protein, selenium, vitamin A, and vitamin E.

Does Enteropathy-Associated T Cell Lymphoma Respond To Gluten-Free Diet?

Strict adherance to the gluten free diet seems to be the only possiblity of preventing this subset of rare, but very aggressive, form of cancer.¹⁸

6 Steps To Improve Enteropathy-Associated T Cell Lymphoma In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both EATL and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.¹⁹
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.²⁰
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.²⁰
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.²⁰.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.²⁰
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.²⁰
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.²⁰[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

 

• [dropcap]4[/dropcap] Manage Your Medications Safely:

[box type=”shadow” ]

Certain medications cause deficiencies of vitamin A, vitamin E, and selenium that predispose to refractory sprue. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete  Vitamin A.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®)  Vitamin A.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Selenium.

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Selenium.

CHOLESTEROL DRUGS

• Colestid® and Questran® deplete Vitamin A, Vitamin E.

FEMALE HORMONES disrupt intestinal permeability which complicate celiac disease.

• Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others) deplete Selenium.
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete.

[/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Vitamin E as prescribed.
• Vitamin A as prescribed following blood test for status.
• Selenium as prescribed following blood test for status.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Enteropathy-Associated T Cell Lymphoma In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study.” This nationwide population study investigating the association between mucosal healing in celiac disease and subsequent lymphoproliferative malignancy found increased risk for T-cell lymphoma, a lymphoproliferative malignancy (LPM), is associated with the follow-up biopsy results, with a higher risk among patients with persistent villous atrophy.

The risk for LPM was compared with that of the general population by using expected rates. The rate of LPM in patients with persistent villous atrophy was compared with that of those with mucosal healing by using Cox regression.

RESULTS: Among 7625 patients with celiac disease and follow-up biopsy, 3308 (43%) had persistent villous atrophy. The overall risk for LPM was higher than that in the general population and was greater among patients with persistent villous atrophy than among those with mucosal healing. Persistent villous atrophy compared with mucosal healing was associated with an increased risk for LPM). The risk for T-cell lymphoma was increased. Follow-up biopsy may effectively stratify patients with celiac disease by risk for subsequent LPM.²¹

“The incidence and clinical spectrum of refractory celiac disease in a north american referral center.” This study investigating medical records of 844 patients diagnosed with celiac disease at a celiac disease referral center in North America found that 4% (34 patients) had refractory celiac disease (RCD) compared to the general celiac disease population. Unintentional weight loss at diagnosis of RCD was found in 76.5% (26 patients) compared with 16.7% (141 patients) at diagnosis of celiac disease and diarrhea at diagnosis of RCD was found in 79.4% (27 patients) compared with 40.5% (342) at diagnosis of celiac disease.

Five patients (14.7%) were diagnosed with RCD type II and of these, two died of enteropathy-associated lymphoma within 24 months of diagnosis of celiac disease (observed mortality rate 5.9%).²²

“Celiac disease and malignancies.” This study investigating the prevalence of cancer in celiac disease found that compared with the general population, patients with celiac disease have an increased risk of developing enteropathy-associated T-cell lymphoma (EATCL), esophageal and pharyngeal squamous carcinomas and small intestinal adenocarcinomas.

At a mean of 13.5 years, mortality overall was 1.9-fold that of the general population (115 deaths observed. 61.8 expected; p < 0.0001). For both sexes the early mortality was much greater than expected, but the excess steadily diminished with time from diagnosis. Much of the increased mortality from malignant disease was accounted for by deaths from lymphoproliferative disease and esophageal cancer. Interim re-analysis after a further 9 years shows that the pattern of later deaths is consistent with these trends.²³

CASE REPORT SUMMARIES

“A rare but potentially fatal cause of diarrhoea and weight loss: enteropathy-associated T-cell lymphoma.“ This case report describes finding celiac disease and enteropathy-associated T-cell lymphoma (EATL) in a patient who presented to the physician with diarrhea and weight loss.  EATL commonly presents with abdominal pain, diarrhea and weight loss, but can also present with complications such as bowel obstruction and perforation. It is the most common neoplastic complication of celiac disease, but can occur with no prior diagnosis of celiac disease.

This case demonstrates the difficulties that can be faced in diagnosing this disorder, particularly when there is no preceding history of celiac disease. Early diagnosis is of utmost importance in order to start treatment before the effects of malnutrition increase the risk of complications from chemotherapy. Hence awareness of the condition among general medical physicians, to whom it will often present first, is essential. However, even with prompt diagnosis, outcomes for this condition remain poor.⁸

“Enteropathy-associated T cell lymphoma as a complication of silent celiac disease. “ This case report describes the unexpected finding of small intestinal lymphoma in a tissue specimen that also revealed villous atrophy in a 69-year old female presenting with complicated celiac disease. The patient was referred following the microscopic examination of an enterectomy specimen, which unexpectedly revealed an enteropathy-associated T cell lymphoma in a background of celiac disease.

The patient’s previous medical history comprised several abdominal surgical procedures without other prior symptoms suggestive of celiac disease. Indeed, the patient was obese and no signs of malabsortion were apparent. This case draws our attention to clinically silent celiac disease, which represents a diagnostic challenge. Thus, this should be kept in mind whenever a patient presents with abdominal relapsing complications, otherwise unexplained.⁹

“Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation.” This case report describes the diagnosis and treatment of a 60-year old male patient who presented with weight loss, rectal bleeding and night sweats. He underwent a CT and MRI scan, which showed circumferential thickening of the jejunum and mesenteric lymphadenopathy. A laparoscopic lymph node biopsy was performed but the histology was inconclusive. Endoscopy and push enteroscopy with biopsies showed multiple jejunal ulcers with histological evidence of celiac disease.

He represented 4 weeks later with massive rectal bleeding and hemodynamic instability and was taken to surgery. On table endoscopy and enteroscopy identified multiple bleeding ulcers in the mid–jejunum and so a jejunal resection and primary anastomosis was performed.
A week post-operatively he developed recurrent rectal bleeding. A colonoscopy, red blood cell (RBC) scan and CT angiography (CTA) were performed but failed to localize the site. Later that day he had further episodes of large volume rectal bleeding and a repeat CTA identified the jejunal anastomosis as the site of bleeding. The anastomosis was resected and the jejunum re-anastomosed. Post-operatively the bleeding settled and he was discharged home 2 weeks later.

Two weeks after discharge he commenced three agent chemotherapy (cyclophosphomide, vincristine, prednisolone). Approximately 10 h after this he developed severe abdominal pain and signs of peritonism. A CT scan showed free intra-peritoneal gas and a re-laparotomy was performed. Two spontaneous small bowel perforations were found proximal and distal to prior small bowel anastomosis and these were oversewn. On the fourth post-operative day he developed malena and rectal bleeding. A CTA showed bleeding from a branch of the superior mesenteric artery, which was embolized with three tornado coils and hemostasis was achieved. A day later however he had ongoing rectal bleeding at which stage a decision was made not to perform any further interventions due to the poor prognosis and he subsequently passed away 3 days later.²⁴

“A case of enteropathy-associated T-cell lymphoma presenting with recurrent hematochezia.”  This case report describes a 60 year old male diagnosed with EATL after segmental small bowel resection, who presented with recurrent bright red blood in his stool due to gastrointestinal bleeding. The clinical course of EATL is very unfavorable and the prognosis is poor. The risk of EATL is markedly increased in celiac disease.²⁵

“Refractory celiac disease, small-bowel lymphoma and chorea.” This case report describes the development of chorea associated with non-Hodgkin’s T-cell lymphoma in a 58 year old woman who was compliant with a gluten free diet since having been diagnosed with celiac disease eleven years earlier upon being investigated for symptomatic anemia and found to be iron and folate deficient. She had no abdominal symptoms. Distal duodenal biopsies showed subtotal villous atrophy, inflammatory infiltration of the lamina propria and an increase in intraepithelial lymphocytes. Celiac disease was diagnosed and she was started on a gluten-free diet. She gained weight and ceased to be anemic; however, repeat biopsies of her duodenal mucosa showed no improvement in the villous atrophy.

Eleven years later she complained of diarrhea, ankle edema and 7 kg weight loss. Endoscopic duodenal biopsies again showed features consistent with untreated celiac disease, and again a dietitian confirmed adherence to a strict gluten-free diet. A barium follow-through showed a rather featureless jejunal mucosa but no obstructive lesion of the small bowel; nothing abnormal was seen on an ultrasound scan of the abdomen. In view of her worsening symptoms despite a gluten-free diet, she was started on prednisolone, initially 30 mg daily, and over the next year her clinical condition improved, with resolution of her diarrhea and a weight gain of 5 kg.

At the time of discontinuation of prednisolone a year later she developed involuntary writhing movements of her left limbs. On examination she had choreo-athetoid movements involving the left limbs and persistent dysarthria. At that time she was taking digoxin, aspirin, ferrous sulphate and thyroxin; she had never received any neuroleptic medication. No underlying neurological disease to explain her chorea was found.
Her chorea continued and seven months later she developed acute abdominal pain. At emergency laparotomy she was found to have a perforated jejunal tumour, which was resected. It proved to be a non-Hodgkin’s T-cell lymphoma. She had intravenous chemotherapy but deteriorated three months postoperatively and died.

“Although her chorea may have been a neurological association of her refractory celiac disease, an alternative explanation is that it was a paraneoplastic complication of her impending T-cell lymphoma. Chorea has been described as a paraneoplastic phenomenon in patients with non-Hodgkin’s lymphoma, but to our knowledge this is the first case where it has been associated with lymphoma arising from a background of celiac disease. The finding of chorea in association with celiac disease should prompt a search for possible underlying intestinal T-cell lymphoma.”²⁶

Sources:

1. Pun AH, Kasmeridis H, Rieger N, Loganathan A. Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩] [↩]
2. Yang DH, Myung SJ, Chang HS, et al. A case of enteropathy-associated T-cell lymphoma presenting with recurrent hematochezia. Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Dec 2003;42(6):527-32. [↩]
3. Meijer JWR, Mulder CJJ, Goerres MG, Boot H, Schweizer JJ. Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment. Scandanavian Journal of Gastroenterology. Dec 2004;39(Suppl 241):78,7p. [↩]
4. Pun AH, Kasmeridis H, Rieger N, Loganathan  Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation.A. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]
5. Peter G. Isaacson. Gastrointestinal lymphoma. Human Pathology. 1994;25(10):1020–1029. [↩]
6. Pun AH, Kasmeridis H, Rieger N, Loganathan A. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]
7. Wright DH. The major complications of coeliac disease. Bailliere’s Clinical Gastroenterology. Jun 1995;9(2):351-69. [↩] [↩]
8. Wali GN, Tyrrell HE, Collins GP, Eagleton HJ. A rare but potentially fatal cause of diarrhoea and weight loss: enteropathy-associated T-cell lymphoma. BMJ Case Rep. 2015 Jan 7;2015. pii: bcr2014204125. doi: 10.1136/bcr-2014-204125. [↩] [↩]
9. Brito MD, Martins Â, Henrique R, Mariz J. Enteropathy-associated T cell lymphoma as a complication of silent celiac disease. Hematol Rep. 2014 Dec 9;6(4):5612. doi: 10.4081/hr.2014.5612. eCollection 2014. [↩] [↩] [↩]
10. Meijer JWR, Mulder CJJ, Goerres MG, Boot H, Schweizer JJ. Coeliac disease and (extra) intestinal T-cell lymphomas: definition, diagnosis and treatment. Scandanavian Journal of Gastroenterology. Dec 2004;39(Suppl 241):78,7p. [↩]
11. Pun AH, Kasmeridis H, R Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]
12. Lebwohl B, Granath F, Ekbom A, Smedby KE, Murray JA, Neugut AI, Green PH, Ludvigsson JF. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med. 2013 Aug 6;159(3):169-75. doi: 10.7326/0003-4819-159-3-201308060-00006. [↩]
13. Kitiyakara T, Jackson M, Gorard DA. Refractory coeliac disease, small-bowel lymphoma and chorea. J R Soc Med. 2002 Mar;95(3):133-4. [↩]
14. Ferguson A, Kingstone K. Celiac disease and malignancies. Acta Paediatr Suppl. 1996 May;412:78-81. [↩]
15. Smedby KE, Akerman N, Hildebrand H, Glimelius B, Ekbom A, Askling J. Malignant lymphomas in celiac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. Jan 2005;54(1):54-59. [↩]
16. Yang DH, Myung SJ, Chang HS, et al. A case of enteropathy-associated T-cell lymphoma presenting with recurrent hematochezia. Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Dec 2003;42(6):527-32. [↩]
17. Meijer JWR, Mulder CJJ, Goerres MG, Boot H, Schweizer JJ. Celiac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment. Scandanavian Journal of Gastroenterology. Dec 2004;39(Suppl 241):78,7p. [↩]
18. Catassi C, Bearzi I, Holmes GK. Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology. Apr 2005;128(4 Suppl 1):S79-86. [↩]
19. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
20. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
21. Lebwohl B, Granath F, Ekbom A, Smedby KE, Murray JA, Neugut AI, Green PH, Ludvigsson JF. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med. 2013 Aug 6;159(3):169-75. doi: 10.7326/0003-4819-159-3-201308060-00006. [↩]
22. Roshan B, Leffler DA, Jamma S, Dennis M, Sheth S, Falchuk K, Najarian R, Goldsmith J, Tariq S, Schuppan D, Kelly CP. The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol. 2011 May;106(5):923-8. doi: 10.1038/ajg.2011.104. [↩]
23. Ferguson A, Kingstone K. Coeliac disease and malignancies. Acta Paediatr Suppl. 1996 May;412:78-81. [↩]
24. Pun AH, Kasmeridis H, Rieger N, Loganathan A. Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation.  J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]
25. Yang DH, Myung SJ, Chang HS, et al. A case of enteropathy-associated T-cell lymphoma presenting with recurrent hematochezia. Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Dec 2003;42(6):527-32. [↩]
26. Kitiyakara T, Jackson M, Gorard DA. Refractory coeliac disease, small-bowel lymphoma and chorea. J R Soc Med. 2002 Mar;95(3):133-4. [↩]