Gluten Free Works: TREATMENT GUIDE Get well and stay healthy living gluten free
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IELs Appear as Dark Spots in this Small Bowel Biopsy Sample. Courtesy Danielle Daitch
What Is Intraepithelial Lymphocytosis In Normal Small Bowel Samples?
Intraepithelial lymphocytosis is characterized by an abnormal increase in the numbers of intraepithelial lymphocytes (IELs) that are present in the small intestinal mucosa.
Q: What are intraepithelial lymphocytes?
A: Intraepithelial lymphocytes are a unique T-lymphocyte (T-cell) population of white blood cells that are normally interspersed between epithelial cells that form the surface mucosa, or inner lining of the small intestinal tract. The cells present in a tissue sample taken by the gastroenterologist during a biopsy procedure are later counted under a microscope by a pathologist in the laboratory to aid diagnosis.
Lymphocytes are specialized cells that are responsible for our immune protection. While only 1% are present in circulating blood, the rest are present mainly in lymphatic tissue. They control the specificity (what will be attacked) and intensity of an immune response by our immune system.
The majority, or about 75%, of lymphocyes are T-lymphocytes (T-cells).
Increased IELs may be associated with autoimmune disorders and non-steroidal anti-inflammatory drugs (NSAID).1
What Is Intraepithelial Lymphocytosis In Normal Small Bowel Samples In Celiac Disease and/or Gluten Sensitivity?
- Intraepithelial lymphocytosis (increased number of intraepithelial lymphocytes) is a feature of celiac disease within the wide spectrum of histological abnormalities observed in celiac disease including a normal villous architecture viewed on biopsy in latent celiac disease.2
- An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies.
- In newly diagnosed celiac disease, some variability of histological lesions can be found, even within the same duodenal biopsy, in which areas of apparently normal mucosa with increased intraepithelial lymphocyte (IEL) number often exist. Previous findings were also confirmed that duodenal lesions may vary among different biopsies; lesion severity has a proximal-to-distal gradient, but no patient has entirely normal duodenal biopsies.3
- However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori-associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Since histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for celiac disease, there will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of celiac disease and lessen diagnostic confusion.4
How Prevalent Is Intraepithelial Lymphocytosis In Normal Small Bowel Samples In Celiac Disease and/or Gluten Sensitivity?
Intraepithelial lymphocytosis can be the initial presentation of celiac disease in 10% of cases.1
What Are The Symptoms Of Intraepithelial Lymphocytosis In Normal Small Bowel Samples?
- Intraepithelial lymphocytosis is asymptomatic by clinical examination, meaning it has no symptoms to alert an investigation.
How Does Intraepithelial Lymphocytosis In Normal Small Bowel Samples Develop In Celiac Disease and/or Gluten Sensitivity?
- Intraepithelial lymphocytosis results from an unclear etiology involving gluten.
Does Intraepithelial Lymphocytosis Respond To Gluten-Free Diet?
Yes. Intraepithelial lymphocytosis has a favorable response to gluten free diet.
6 Steps To Improve Intraepithelial Lymphocytosis In Celiac Disease and/or Gluten Sensitivity:
- 1Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:
- 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.5
- The intestinal lining may take up to a year to heal.
- 2 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).
- Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.6
- 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.6
- 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.6.
- 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.6
- 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.6
- Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.6
- Cocoa and Black Tea increase blood sugar.
- Rosemary. Increases blood sugar levels and should not be used by persons with insulin resistance or diabetes.
- 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.
- 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:
- 4 Manage Your Medications Safely:
Certain medications promote intraepithelial lymphocytosis. 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.
ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.
- NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) also deplete Folic acid.
- 5Nutritional Supplements To Help Correct Deficiencies:
The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.
- Multivitamin/mineral combination that provides 100% 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.
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.
- 6Manage Natural Remedies:
- 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.
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. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabete.
- 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.
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.
What Do Medical Research Studies Tell About Intraepithelial Lymphocytosis In Normal Small Bowel Samples In Celiac Disease and/or Gluten Sensitivity?
RESEARCH STUDY SUMMARIES
“How patchy is patchy villous atrophy?: distribution pattern of histological lesions in the duodenum of children with celiac disease.” This prospective study evaluated the degree, frequency, and distribution of histological lesions among different duodenal sites as well as within each duodenal biopsy. In newly diagnosed celiac disease, some variability of histological lesions can be found, even within the same duodenal biopsy, in which areas of apparently normal mucosa with increased intraepithelial lymphocyte (IEL) number often exist. Previous findings were also confirmed that duodenal lesions may vary among different biopsies; lesion severity has a proximal-to-distal gradient, but no patient has entirely normal duodenal biopsies.
Over the last 4 years, in each patient with suspected celiac disease (positive anti-transglutaminase antibodies), 4 to 5 endoscopic biopsies were taken from the duodeno-jejunal flexure/distal duodenum (D3), intermediate duodenum (D2), proximal duodenum (D1), and duodenal bulb (B). Biopsies were subjected to hematoxylin/eosin staining and immunostaining with anti-CD3 monoclonal antibodies for intraepithelial lymphocyte (IEL) count. Duodenal lesions were classified according to Marsh-Oberhuber, and CD was diagnosed according to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria.
Of 686 children with celiac disease, a degree of villous atrophy was found in 660/686 patients (96.2%), total villous atrophy was present in 550/686 (80.1%), and 320/686 (46.6%) had different lesions at different sites, but none of these patients had entirely normal biopsies. In all, 116 of 686 (16.9%) had variable lesions within the same biopsy, with grade 2+3A being the most frequent association (43%), followed by 2+3A+3B (27%) and 2+3A+3B+3C (22%). All these 116 patients also had histologically normal areas within the same biopsy, but anti-CD3 immunostaining showed that IELs were always increased in such areas. In all the cases, the severity of duodenal lesions significantly increased in an aborad manner (chi(2)=52.38 with alpha=0.01 and d.f.=12; P<0.0001). No correlation was found between type and distribution of histologic lesions and clinical presentation of celiac disease.3
“Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture.” This study investigating the specificity of increase in intraepithelial lymphocytes (IELs) for diagnosis of gluten sensitivity (GS) in an otherwise normal small bowel biopsy concluded it is somewhat non-specific for GS but, because of the prevalence of GS, all patients with this finding should be investigated for GS. Increased IELs may also be associated with autoimmune disorders and non-steroidal anti-inflammatory drugs (NSAID).1
“Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant?” This study investigatig the frequency of a raised intraepithelial lymphocyte (IEL) count with normal villous architecture in routine practice and to determine whether it is clinically relevant found that a raised IEL count with normal villous architecture is not uncommon. Six of the 14 patients may have had latent celiac disease. The cause in at least half of cases is not obvious at present. The finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be highlighted in routine duodenal biopsy reports.
Patients with subjectively increased IELs as the only abnormality were identified prospectively from a routine duodenal biopsy series over a 12 month period. The biopsy specimens in these index cases were re-examined together with two controls with normal histology for each case, and three counts of IEL/100 epithelial cells were made in all samples. The index cases were then contacted and interviewed to obtain clinical information, approximately 12 months from the initial biopsy. Further data were obtained from their clinical records. Fourteen of 626 (2.2%) patients who had duodenal biopsies over the 12 month period had a subjective increase in IELs with normal villous architecture. Fifteen patients with newly diagnosed gluten sensitive enteropathy were also identified during the study period.
Formal counting of the index cases and controls revealed a significant difference in IELs/100 epithelial cell counts between the two. Three of the 14 index cases tested had a positive celiac antibody test compared with 12 of 15 newly diagnosed patients with celiac disease and 10 of 93 patients with normal histology. The major clinical diagnostic categories in raised IEL cases were those with positive celiac serology (3), unexplained anemia (3), and chronic liver disease (3). Six of 10 patients who were interviewed had ongoing gastrointestinal symptoms one year later.7
- Kakar S, Nehra V, Murray JA, Dayharsh GA, Burgart LJ. Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. The American Journal of Gastroenterology. Sep 2003;98(9):2027-33. [↩] [↩] [↩]
- Mahadeva S, Wyatt JI, and Howdle PD. Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant? J Clin Pathol. 2002 June; 55(6): 424–428. PMCID: PMC1769667 [↩]
- Ravelli A, Villanacci V, Monfredini C, Martinazzi S, Grassi V, Manenti S. How patchy is patchy villous atrophy?: distribution pattern of histological lesions in the duodenum of children with celiac disease. Am J Gastroenterol. 2010 Sep;105(9):2103-10. doi: 10.1038/ajg.2010.153. [↩] [↩]
- Chang F, Mahadeva U, Deere H. Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa. APMIS. 2005 Jun;113(6):385-99. [↩]
- 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. [↩]
- 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. [↩] [↩] [↩] [↩] [↩] [↩]
- Mahadeva S, Wyatt JI, and Howdle PD. Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant? J Clin Pathol. 2002 June; 55(6): 424–428. PMCID: PMC1769667 [↩]
