Gluten Sensitive Enteropathy (Active Celiac Disease)

What Is Gluten Sensitive Enteropathy?

Gluten sensitive enteropathy is active celiac disease characterized by inflammation of the small intestinal mucosa that results from an inherited immunologic intolerance to ingested gluten.

Q: What does the inflammation do to the mucosa in the small intestine?

A: Inflammation is a cell level immune response to gluten that has these effects on the mucosa:

• Damages the barely visible villi (multitudinous finger-like structures) by causing atrophy or loss.
• Likely affects the structural support and microcirculation of the villus, leading to collapse of the villus.
• Elongates the crypts between villi. The thickening of the crypt is not so much a response to loss of surface enterocytes but represents inflammation of the mucosa.¹
• Increases round cells in the lamina propria and surface epithelial cells leaving few, irregular microvilli (brush border) on the surface of villi.
• Damage is most intense in the duodenum and decreases toward the large intestine.
• The extent of the damage to the intestine determines the malabsorptive consequences of the disease. Both gastric and small intestinal permeability are disrupted in patients with celiac disease.²

• Relationship between active celiac disease and intestinal permeability: There is a clear association between degree of mucosal damage and the intestinal-permeability ratio, and a normal ratio generally implies near-normal small intestinal structure. A raised intestinal permeability of the mucosal lining (leaky gut) could predispose to a high absorption of gluten and exacerbate an existing lesion and hence convert a latent to an overt enteropathy.³
• Relationship between active celiac disease and tight junction proteins: A study of intestinal permeability showed that the expression of all junction proteins of the small intestinal lining (occludin, claudin 3, zonula occludens 1, and E-cadherin) was already decreased in early stage celiac disease when compared with non-celiac controls, showing leaky gut and confirming the above earlier study by Johnston et al. Junction protein expression correlated positively with mucosal villus structure and negatively with the number of intraepithelial lymphocytes (IELs), the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score.⁴
• Relationship between active celiac disease and inflammation. In celiac disease there is an over production of inflammatory interleukin-15 (IL-15) which inhibits the correct removal of damaged intraepithelial lymphocytes caused by the reaction to gluten. Serum levels of IL-15 are directly correlated with the seriousness of tissue damage.⁵

• Relationship between active celiac disease and gut microbiota. Results of a study investigating intestinal microbiota (normal bacterial residents) in patients with celiac disease suggest that with lower levels of the genus bifidobacteria, celiac patients have an imbalance in the intestinal microbiota even while on a gluten-free diet. This fact could favor the pathological process of the disorder. The concentration of bifidobacteria per gram of feces was significantly higher in healthy subjects (2.5 ± 1.5 x107 CFU/g) when compared to celiac patients (1.5 ± 0.63 x108 CFU/g).⁶

• Relationship between active celiac disease and endoscopy technique. The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o’clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o’clock position biopsy and the 3-o’clock position biopsy in detecting the most severe villous atrophy was 92% (24/26 patients) versus 65% (17/26 patients).⁷
• Relationship between active celiac disease and diet adherence. Patients with consistent gluten free diet adherence experience symptomatic responses to dietary gluten (SRDG) faster and more severe in comparison to their prior gluten exposure possibly demonstrating an adept immunological response. Anxiety and depression also enhance the speed of symptom onset and co-existing visceral hypersensitivity is a risk factor for severe reactions to dietary gluten.⁸
• Relationship between active celiac disease and atrial fibrillation: Patients with celiac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation.⁹

How Prevalent Is Gluten Sensitive Enteropathy?

• Gluten sensitive enteropathy is present in all patients with active celiac disease.²
• Prevalence of celiac disease among children with abdominal pain-related functional gastrointestinal disorders classified according to the Rome criteria as IBS  is 4.4%. Prevalence is 4 times higher than among the general pediatric population.¹⁰

What Are The Symptoms Of Gluten Sensitive Enteropathy?

Gluten sensitive enteropathy is usually, but not always, marked by gastrointestinal distress including these symptoms:

• Abdominal pain – 70.0% in classic CD; 76.9% in atypical CD children.
• Abdominal distention.
• Diarrhea – 90.0% in classic CD children.
• Constipation – 25% in atypical CD children.
• Steatorrhea.
• Weight loss in a third.
• Failure to thrive in children – 10% in classic CD; 38.4% in atypical CD children.
• Weight gain or obesity in a third.
• Anemia – 15.3% in atypical CD children.
• Hypocholesterolemia – 35.0% in classic CD children.
• hypercholesterolemia – 33.3% in silent CD children.
• Hypertransaminasemia – 11.5% atypical CD children.
• Food allergy – 19.2% in atypical CD children.
• Vomiting – 39.6 % in atypical CD children.
• Deficiencies of carbohydrate, protein, fat and fat-soluble vitamins D,E,A, and K, iron, zinc, folic acid, and calcium are common.
• A wide spectrum of both pathophysiologic changes in the intestines and clinical syndromes may develop.¹¹

How Does Gluten Sensitive Enteropathy Develop?

• Gluten sensitive enteropathy results from an active immune response to dietary gluten exposure in the small intestinal mucosa .

Does Gluten Sensitive Enteropathy Respond To A Gluten-Free Diet?

Functional recovery occurs early on a gluten free diet and precedes small intestinal tissue recovery which is often incomplete.¹²

6 Steps To Improve Gluten Sensitive Enteropathy:

• [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 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.¹³
• 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.¹⁴
• 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.¹⁴
• 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.¹⁴.
• 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.¹⁴
• 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.¹⁴
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹⁴
• Cocoa and Black Tea increase blood sugar.
• Rosemary. Increases blood sugar levels and should not be used by persons with insulin resistance or diabetes. [/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:

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Certain medications aggravate gluten sensitive enteritis and/or deplete nutrients which worsens malnutrition.  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 Calcium, Chromium, Coenzyme Q10, Folic Acid, Iron, Vitamin A, Vitamin B12, Vitamin D, Zinc, Magnesium, Copper, Potassium.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Calcium, Chromium, Folic Acid, Iron, Vitamin A, Vitamin B12, Vitamin D, Zinc, Magnesium, Copper, Potassium, Phosphorus.
• Prevacid®, Prilosec® deplete Coenzyme Q10,Vitamin B12.
• Alka Seltzer®, Baking Soda deplete Coenzyme Q10, Folic Acid, Magnesium, Proteins, Potassium.

ANTI-DEPRESSANTS

• Adapin®, Aventyl®, Elavil®, Pamelor®, Paxil®, Zoloft®, and others deplete Coenzyme Q10, Vitamin B12, Riboflavin.

ANTIBIOTICS disrupt intestinal permeability which complicates celiac disease.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete B Vitamins, Vitamin K, Probiotics, Vitamin C.
•  Tetracyclines deplete Coenzyme Q10, Calcium, Magnesium, Iron, Vitamin B6, Zinc, Probiotics, Riboflavin.
• Cipro depletes Coenzyme Q10, Zinc.
• Dapsone depletes vitamin K.
• Penicillins deplete Vitamin B2, Folic Acid, Vitamin B12, Biotin, Vitamin K, Probiotics.¹⁵
• Erythromycin depletes Vitamin B2, Folic Acid, Vitamin B12, Biotin, Vitamin K, Probiotics.¹⁶

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Calcium, Vitamin D, Magnesium, Zinc, Vitamin C, Vitamin B6, Vitamin B12, Folic Acid, Selenium, Chromium, Phosphorus.
• NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.
• Aspirin and Salicylates deplete Calcium, Folic acid, Vitamin C, Iron, Pantothenate (vitamin B5).

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Calcium, Vitamin D, Folic Acid, Biotin, Carnitine, Vitamin B12, Vitamin B1, Vitamin K, Copper, Selenium, Zinc.

ANTIVIRAL AGENTS

• Zidovudine (Retrovir®, AZT and other related drugs) deplete Carnitine, Copper, Zinc, Vitamin B12.
• Foscanet depletes Calcium, Magnesium, Potassium. 

BRONCHODILATORS

• Inhaled corticosteroid inhalers (Flovent, Pulmicort and others) that are breathed in on a daily basis as a long term therapy to reduce inflammation in airways deplete Potassium, Calcium, Vitamin D, and B vitamins.
• Albuterol inhalers that are breathed in on a daily basis as a long term therapy and also for quick relief as rescue inhalers to open airways depletes Potassium, Magnesium, Calcium.
• Theophylline by mouth as a long term therapy to open airways depletes Potassium.

CARDIOVASCULAR DRUGS

• Antihypertensives (Catapres®, Aldomet) deplete Coenzyme Q10, Vitamin B6, Vitamin B1 Zinc.
• ACE Inhibitors (Capoten®, Vasotec®, Monopril® and others) deplete Zinc.
• Beta blockers (Inderol®, Lopressor®, Corgard®, Atenolol®) deplete Coenzyme Q10, Melatonin.

CHOLESTEROL DRUGS

• Lipitor®, Crestor®, Zocor®, and others deplete Coenzyme Q10, Phosphorus.
• Colestid® and Questran® deplete Vitamin A, Vitamin B12, Vitamin D, Vitamin E, Vitamin K, Beta-carotene, Folic Acid, Iron.

DIABETIC DRUGS 

• Metformin® depletes Coenzyme Q10, Folic acid, Vitamin B12.

DIURETICS

• Thiazide Diuretics (Hydrochlorothiazide, Enduron®, Diuril®, Lozol®, Zaroxolyn®, Hygroton® and others) deplete Coenzyme Q10, Magnesium, Potassium, , Zinc, Phosphorus.
• Loop Diuretics (Lasix®, Bumex®, Edecrin®) deplete Calcium, Magnesium, Vitamin B1, Vitamin B6, Vitamin C, Coenzyme Q10, Potassium, Sodium, Zinc, Phosphorus.
• Potassium Sparing Diuretics (Midamor®, Aldactone®, Dyrenium® and others) deplete Calcium, Folic Acid, Zinc.

FEMALE HORMONES disrupt intestinal permeability which complicate celiac disease.

• Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others) deplete Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B12, Vitamin C, Folic Acid, Magnesium, Selenium, Zinc.
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Folic Acid, Magnesium, Zinc.

LAXATIVES

• Metamucil, FiberCon, Citrucel, Colace, Glycolax, Milk of magnesia, Dulcolax deplete: Vitamins A, Vitamin D, Vitamin E, Calcium, Sodium, Potassium.

MAJOR TRANQUILIZERS  

• Thorazine®, Mellaril®, Prolixin®, Serentil® and others deplete Coenzyme Q10, Vitamin B2.

WEIGHT LOSS DRUGS THAT BIND FAT also interfere with absorption of some nutrients.

• Zenicol (Orlistat®) depletes Vitamin A, Vitamin D, Vitamin E, Vitamin K, Beta-carotene.

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

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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.
• Calcium citrate is the best absorbed of calcium supplements. Calcium carbonate is a poor choice.
• Vitamin D3 as prescribed following blood test for status.
• Chelated magnesium  as prescribed but do not take at same time as calcium because they compete for absorption.
• Others as needed.

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. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabetes.
• 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 Gluten Sensitive Enteropathy?

RESEARCH STUDY SUMMARIES

“Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease.” This study investigating whether alterations in epithelial junction protein expression of the small intestinal lining occur already in early stage celiac disease with normal mucosal morphology, and whether this correlates with inflammation indicators and clinical symptoms demonstrated that the mucosal epithelial integrity is disrupted already in early stage celiac disease before the disorder progresses to full-blown enteropathy.

The study involved 10 patients with early stage and 10 patients with overt villus atrophy that were followed yearly according to the study protocol. As controls, 20 non-celiac subjects were included. The expression of junction proteins (occludin, claudin 3, zonula occludens 1, and E-cadherin) was studied in small-intestinal biopsies using immunohistochemistry and Western blot. The correlation between junctional proteins and mucosal morphology, autoantibodies, the number of intraepithelial lymphocytes (IELs), and gastrointestinal symptoms was assessed.

The expression of all junction proteins was already decreased in early stage celiac disease when compared with non-celiac controls. Junction protein expression correlated positively with mucosal villus morphology and negatively with the number of IELs, the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score (R = -0.314, P = 0.04).⁴

“Lower bifidobacteria counts in adult patients with celiac disease on a gluten-free diet.” This study investigated the concentration of fecal bifidobacteria (normal gut bacteria) and pH (acid/alkaline level) of patients with celiac disease on gluten-free diet and control subjects in order to identify if the imbalance on fecal microbiota still remain during the treatment of celiac disease and identify the necessity of dietary supplementation with pre- or probiotics. Results suggest that with lower levels of bifidobacteria, celiac patients have an imbalance in the intestinal microbiota, regardless of pH, even while on a gluten-free diet. This fact could favor the pathological process of the disorder.

Feces of 42 healthy subjects and 14 celiac patients were analyzed. The bifidobacteria count in feces was done in selective medium BIM-25. Microscopic analysis of the colonies was performed by Gram stain. The identification of the genus Bifidobacterium was performed by determination of fructose-6-phosphate phosphoketolase. Fecal pH was measured using a pH meter.

The concentration of bifidobacteria per gram of feces was significantly higher in healthy subjects (controls) (2.5 ± 1.5 x107 CFU/g) when compared to celiac patients (1.5 ± 0.63 x108 CFU/g). The fecal pH was not different between celiac patients (7.19 ± 0.521) and controls (7.18 ± 0.522).⁶

“Increased prevalence of celiac disease among pediatric patients with irritable bowel syndrome: a 6-year prospective cohort study.” This study investigating the prevalence of celiac disease among children with abdominal pain-related functional gastrointestinal disorders classified according to the Rome criteria found that the prevalence of celiac disease among children with IBS is 4 times higher than among the general pediatric population. Rome III classification of abdominal pain-related functional gastrointestinal disorders might help to select children who deserve screening for celiac disease.

This was a six-year (2006-2012) prospective cohort study conducted in a tertiary referral center (hospital) for the diagnosis and follow-up of gastrointestinal disorders in southern Italy (i.e., Bari, Italy). A total of 992 children (42.8% male; median age, 6.8 years) consecutively referred for recurrent abdominal pain by their primary care physicians without previous investigation were evaluated.

Patients were classified according to Rome III criteria as having IBS, functional dyspepsia, functional abdominal pain, or abdominal migraine. Prevalence of celiac disease in each category of abdominal pain-related functional gastrointestinal disorder was evaluated. Concentrations of IgA, IgA antitissue transglutaminase, and endomysial antibodies were measured, and a duodenal biopsy was performed in case of antibody positivity.

Of 992 children who were evaluated: 270 were classified as having IBS, 201 as having functional dyspepsia, and 311 as having functional abdominal pain, and 210 children were excluded from the study because they had an organic disorder or some other functional gastrointestinal disorder (not related to abdominal pain). Serologic testing was performed for all 782 children included in the study, and 15 patients tested positive for celiac disease (12 of 270 patients with IBS [4.4%], 2 of 201 patients with functional dyspepsia [1%], and 1 of 311 patients with functional abdominal pain [0.3%]).¹⁰

“Differentiating coeliac disease from irritable bowel syndrome by urinary volatile organic compound analysis – a pilot study.” This study investigated if celiac disease, which causes altered gut fermentation patterns recognizable by volatile organic compounds (VOC) in urine, breath and feces, can be distinguished from irritable bowel disease (IBS) by a new test called Field Asymmetric Ion Mobility Spectrometry (FAIMS). This test analyzes the urinary (VOC) pattern. This study suggests that FAIMS offers a novel, non-invasive approach to identify those with possible celiac disease, and distinguishes from D-IBS. It offers the potential for monitoring compliance with a gluten-free diet at home.

Recruited were 47 patients: 27 with established celiac disease, on gluten free diets, and 20 with diarrhoea-predominant IBS (D-IBS). Collected urine was stored frozen in 10 ml aliquots. For assay, the specimens were heated to 40±0.1°C and the headspace analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Machine learning algorithms were used for statistical evaluation. Samples were also analysed using Gas chromatography and mass spectroscopy (GC-MS).

Sparse logistic regression showed that FAIMS distinguishes VOCs in celiac disease vs D-IBS with ROC curve AUC of 0.91 (0.83-0.99), sensitivity and specificity of 85% respectively. GCMS showed a unique peak at 4’67 found only in celiac disease, not D-IBS, which correlated with the compound 1,3,5,7 cyclooctatetraene. The presence of cyclooctatetraene in celiac disease specimens will need further validation.¹⁷

“Clinical picture of classical, atypical and silent celiac disease in children and adolescents.” This study investigating clinical findings, selected laboratory features and coexisting diseases in 78 children aged 8 months – 13 years with celiac disease found that classical celiac disease was diagnosed in 40 children (51.3%), atypical celiac disease in 26 children (33.3%) and silent celiac disease in 12 children (15.4%).

The most frequent clinical symptoms of classical form of celiac disease were chronic diarrhea (90.0%), recurrent abdominal pain (70.0%), development retardation (65%), hypocholesterolemia (35.0%) and IgA deficiency (22.5%).

In atypical form of the disease dominated the following symptoms: recurrent abdominal pain (76.9%), failure to thrive (38.4%), short stature (42.3%), anemia (15.3%), hypertransaminasemia (11.5%), food allergy (19.2%) and thyroid diseases (11.5%). In silent celiac disease hypercholesterolemia was present in 33.3%, hypertriglycerydemia in 16.6%, type 1 diabetes in 50%, and celiac disease in parents or siblings in 33.3%.¹⁸

“Factors influencing the type, timing and severity of symptomatic responses to dietary gluten in patients with biopsy-proven coeliac disease.” This study investigating the type, timing and severity of symptomatic responses (SRDG) to dietary gluten with reference to a range of disease-related factors found that patients with consistent gluten free diet adherence experience a SRDG faster and more severe in comparison to prior gluten exposure possibly demonstrating an adept immunological response. Anxiety and depression also enhance the speed of symptom onset and co-existing visceral hypersensitivity is a risk factor for severe reactions to dietary gluten.

Method of study: Postal survey of 224 biopsy-proven patients including gluten-free diet adherence, symptom checklist, ROME II criteria and The Hospital Anxiety & Depression Scale. Case-note review was also conducted.

26% of respondents were male. Full gluten free diet adherence numbered 159 (70%). Irritable bowel syndrome (IBS) numbered 50 (22%). Anxiety numbered 30 (13%); Depression numbered 33 (14%); Anxiety & Depression numbered 72 (32%). Pruritus, fatigue and bloating were a more common SRDG in the partial/none gluten free diet adherent group. Co-existing IBS was associated with a greater prevalence of nausea and fatigue in response to gluten.

Fully gluten free diet adherent patients are more likely to have SRDG less than 1hr than partial/none adherent as are a third of patients with co-existing IBS and those patients at risk of both anxiety and depression. Inadvertent exposure to dietary gluten in the fully gluten free diet adherent group is more likely to result in a severe SRDG in comparison to symptoms arising prior to consistent gluten free diet adherence. IBS sufferers are also more likely to rate their SRDG as severe in nature.⁸

“Interprovider variation of celiac disease testing in childhood chronic abdominal pain.” This study investigating interprovider variation among 16 pediatric gastroenterologists and one nurse practitioner for celiac disease testing in 160 children with chronic abdominal pain found that a large number of these children were not evaluated for celiac disease. Celiac disease was ultimately diagnosed in 4 (4.9%) of the 82 tested with all 4 having Marsh grade 3 histo-pathologic findings.

Lack of uniform testing among the providers for the children evaluated suggests these providers are selective in their approach; therefore, recommendations regarding uniform celiac testing in this population are not currently being followed. There was a trend toward increased frequency of serologic testing in those children with diarrhea, bloating, and flatus. Interestingly, flatus was found to occur significantly more frequently in those with celiac disease.¹⁹

“Presentation of celiac disease.” The mode of presentation of patients with celiac disease has changed dramatically over the recent decades, with diarrheal or classic presentations becoming less common. This trend is most markedly seen in children, whose main presentations include recurrent abdominal pain, growth issues, and screening groups at risk. Among adults, presentations include diarrhea, anemia, osteoporosis, and recognition at endoscopy performed for gastroesophageal reflux disease, as well as screening. The groups most commonly screened include family members of patients with celiac disease, Down syndrome, and autoimmune diseases.²⁰

“Age-related patterns in clinical presentations and gluten-related issues among children and adolescents with celiac disease.” This study performed as a structured medical record review of biopsy-proven celiac disease patients, aged 0-19 years, between 2000 and 2010 at a large Boston teaching hospital showed that children and adolescents with celiac disease have age-related patterns in both the clinical presentations and gluten-related issues.

Patients were divided into three age groups for comparisons of characteristics: infant-preschool group (0-5 years), school-aged group (6-11 years), and adolescence group (12-19 years). Among 411 children with biopsy-proven celiac disease and positive celiac disease-specific serology, most children presented with either abdominal complaints or bowel movement changes. More pronounced gastrointestinal presentations such as abdominal distention, vomiting, bowel movement changes, or weight issues (weight loss or poor weight gain) were in the younger age group.

Whereas two-thirds of the school-aged group had complaints of subjective abdominal complaints (pain, discomfort, gas, and bloating) at the initial presentation, which was more common than the other two groups.  Conversely, the adolescents were most likely to present without any gastrointestinal symptoms, but not when this was combined with absence of weight issues.²¹

“Celiac disease presentation in a tertiary referral centre in India: current scenario.” This facility-based retrospective observational study compared the clinical spectrum of nondiarrheal celiac disease  (NDCD) with that of diarrheal/classical celiac disease (CCD) included consecutive patients diagnosed with celiac disease (as per modified ESPGHAN criteria) from October 2009 to August 2011. A total of 381 patients were diagnosed with celiac disesse during the study period. NDCD was present in 192 (51.8 %). NDCD had higher mean age at presentation (5.8 years vs. 6.9 years respectively) and longer duration of symptoms prior to diagnosis (2.9 years vs. 3.6 years; as compared to CCD.

In the NDCD group, the most frequent gastrointestinal symptoms were recurrent abdominal pain in 122 patients (63.5%) and abdominal distension in102 (53.1 %) followed by constipation in 48 (25 %), vomiting in 76 (39.6 %) and recurrent oral ulcers in 89 (46.4 %). Vomiting and constipation were more frequently seen in NDCD as compared to CCD .  The number of patients with a Marsh score IIIb and above of duodenal biopsy was significantly more in the CCD group. NDCD is not uncommon in India. Long-term follow up is needed to evaluate the impact of the disease and of treatment in these children.²²

“Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site?” This prospective cohort study at a tertiary-care referral center (hospital) investigating whether a targeted duodenal bulb biopsy in addition to distal duodenal biopsies is the optimal strategy to identify villous atrophy demonstrated the patchy appearance of villous atrophy that occurs within the duodenum. “A targeted duodenal bulb biopsy from either the 9- or 12-o’clock position in addition to distal duodenal biopsies may improve diagnostic yields by detecting the most severe villous atrophy within the duodenum.”

Seventy-seven patients undergoing clinically indicated endoscopy (EGD) with duodenal biopsies were recruited. Of these, 28 had newly diagnosed celiac disease and 49 were controls. At endoscopy, 8 duodenal biopsy specimens were taken: 4 from the second part of the duodenum and 4 quadrantically from the bulb (at the 3-, 6-, 9-, and 12-o’clock positions).

The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o’clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o’clock position biopsy and the 3-o’clock position biopsy in detecting the most severe villous atrophy was 92% (24/26) versus 65% (17/26) (P = .02).⁷

“Prevalence of celiac disease in Iranian children with recurrent abdominal pain referred to a pediatric referral center.” The aim of this study was to determine prevalence of celiac disease in Iranian children presenting with functional abdominal pain (FAP). In this cross-sectional study, 301 children affected by FAP were screened for celiac disease by anti-tissue transglutaminase antibody (tTG IgA). IgA antibody was also measured to exclude IgA deficiency.

The antibodies were measured by enzyme linked immunosorbent assay. Diagnosis of celiac disease was confirmed by duodenal biopsy that was scored according to the Marsh classification in cases with abnormal titer of tTG antibody. Two out of 301 cases were IgA deficient and celiac disease was suspected for one of them based on histological findings. Four out of 299 patients with normal IgA had abnormal tTG titer; intermediate ranges (16-23 U/ml) were detected in 1 and positive ranges (24 U/ml) in 3 cases. Celiac disease was suggested in all patients with abnormal titer of tTG (1.33%) based on histological findings. The prevalence of celiac disease in children with FAP is estimated 1.3% (nearly 2 times higher than in normal population) in Iran.²³

“Increased risk of atrial fibrillation in patients with celiac disease: a nationwide cohort study.” This study investigating the association between celiac disease and atrial fibrillation in a large cohort of patients with biopsy-verified celiac disease showed that atrial fibrillation is more common both before and after diagnosis in patients with celiac disease though the excess risk is small. Potential explanations for the increased risk of atrial fibrillation in celiac disease include chronic inflammation and shared risk factors.

Study identified 28,637 patients with celiac disease through biopsy reports (defined as Marsh 3: villous atrophy) from all 28 pathology departments in Sweden. Age- and sex-matched reference individuals (n = 141,731) were identified from the Swedish Total Population Register. Data on atrial fibrillation were obtained from the Swedish Hospital Discharge Register, the Hospital Outpatient Register, and the Cause of Death Register. Hazard ratios (HRs) for atrial fibrillation were estimated using Cox regression. In the celia desease cohort, 941 individuals developed atrial fibrillation during a median follow-up of 9 years. The corresponding adjusted HR for AF was 1.34. The absolute risk of atrial fibrillation in celiac disease was 321 of 100,000 person-years, with an excess risk of 81 of 100,000. A prior atrial fibrillation diagnosis was also associated with an increased risk of subsequent celiac disease.

“Our results indicate that patients with celiac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation. Additional studies are needed to clarify the mechanistic link between atrial fibrillation and autoimmune diseases such as coeliac disease.”⁹

“Celiac disease: clinical features in adult populations.” This retrospective study investigating the incidence and clinical manifestations of celiac disease in adults in Spain who were diagnosed with celiac disease between January 1990 and December 2008 found that celiac disease can appear at any age and with a wide manifestation spectrum, which can be atypical in some cases. Sixty eight adult patients were diagnosed of celiac disease in this period. Mean age was 33 (18-65) years and 50 (74%) were women. The clinical manifestations were diarrhea in 38 (55%), abdominal pain in 27 (40%), loss of weight in 15 (22%), dyspepsia in 13 (19%). Analytical results showed a slight increase of transaminases in 26 (38%), ferropenic (low iron) anemia in 33 (48.5%) cases, sub-clinical hypothyroidism in 3 (4.5%) patients, and folic acid deficiency in 16 (23.5%) cases. Population-based incidence of celiac disease in adults had increased from 0.7-2/100,000 per year in the nineties to 3.5-10.3/100,000 in the last years.²⁴

“Celiac Disease: Presentation of 109 Children.” In this study, clinical and laboratory features of 109 patients with celiac disease were retrospectively evaluated (reveiwed) to determine presentation and manifestations. Of 109 patients with celiac disease, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 ± 4.63 years (range 1.5-17 years) and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and 40.4% with abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings.²⁵

CASE REPORT SUMMARIES

“Pericardial effusion in celiac disease.” This case report describes diagnosis of celiac disease in a 40-year-old woman with progressive fatigue and pitting edema in her lower extremities. Iron deficiency anemia and celiac disease were diagnosed on the basis of low serum ferritin, elevated serum level of IgA endomysial and tissue transglutaminase anti-bodies and histologic findings in small bowel biopsies. Pericardial effusion in her evaluation was detected incidentally. Asymptomatic pericardial effusion in this patient was only detectable with imaging.

After starting of gluten free diet and iron supplement fatigue, peripheral edema and pericardial effusion on echocardiography decreased. It should be noted that asymptomatic pericardial effusion may be seen in adults with celiac disease.²⁶

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