Celiac Disease
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Celiac disease is also known as celiac sprue or gluten enteropathy.  It is caused by an autoimmune allergic reaction to gluten, a protein found in wheat, rye, and barley, in genetically susceptible individuals.  It is a common illness, present in 0.5% to 1.0% of Americans.  

While chronic diarrhea sometimes with weight loss are the most common symptoms leading to diagnosis, most celiac patients won't have diarrhea, so the diagnosis usually missed.  Chronic fatigue, infertility, mild abdominal symptoms, iron-deficiency anemia, or a family history may be the main symptom.  In fact, most CD patients are never diagnosed.  While these may have more mild consequences, their difficulties may still impair their lives.  The disease can start in childhood or later adulthood.  

Hair loss, osteopororsis, or increased red cell width (B-12 deficiency) may be uncommon presentations.  Iron-deficiency anemia and osteoporosis are higher in celiac disease patients due to malabsorption.  Carnitine and selenium levels also tend to be reduced.  The low carnitine levels may be a cause of the fatigue. In a study of 333 patients with iron or folate deficiencies, 11% tested positive for CD antibodies (J Clin Pathol. 2002 Oct;55(10):754-7).  An itchy, blistery rash call dermatitis herpetiformis sometimes accompanies CD.

The diagnosis is most easily made by testing for tissue antitransglutaminase (tTG) or IgA anti-endomysial antibodies.  Anti-tTG antibody testing is a very sensitive (96%), quite specific (99%), and inexpensive screening test for CD (Scand J Gastroenterol. 2002 Jun;37(6):679-84).  Since celiac disease is an auto-immune disease, it is sometimes accompanied by other auto-immune diseases, such as diabetes type 1 in childhood, autoimmune thyroiditis, scleroderma, lupus, autoimmune cholestasis, etc. Non-alcoholic fatty liver disease is also slightly elevated.

While iron-deficiency anemia can be caused by decreased iron absorption in celiac disease, bleeding into the bowel and positive fecal occult blood tests are no more common in CD than in the general population.  Psoriasis can be associated with celiac disease and sometimes resolves on the gluten-free diet.  Another rash called herpetiform dermatitis is associated with CD and usually resolves on the diet.  Autoimmune thyroiditis is also associated with CD.  CD can caused ataxia and peripheral neuropathy with the presence of anti-ganglioside antibodies.  CD is the most common cause of sporadic idiopathic ataxia.  Six of 26 had axonal dysfunction on needle EMGs (J Neurol Neurosurg Psychiatry. 2003 Apr;74(4):490-4).  This could be due to carnitine deficiency due to malabsorption.

Roughly 16% of people with chronic diarrhea or irritable bowel syndrome have CD.  In one study, four of 90 migraine patients tested positive for CD and improved on a gluten-free diet (Am J Gastroenterol. 2003 Mar;98(3):625-9).  Reflex esophagitis was present in 19% of new CD patients with 75% resolving on a gluten-free diet (Gut. 2003 Apr;52(4):514-7).  Screening first degree relatives of CD patients finds 8% positive, about 8 times the normal rate.  

Villous atrophy usually recovers fairly quickly on a gluten-free diet (Int J Surg Pathol. 2001 Oct;9(4):261-4), but at least half still have some damage, especially those not sticking closely to the diet.  In 7-year follow-up of 390 adult CD patients, intestinal damage was severe in 24%, primarily due to poor dietary compliance (Digestion. 2002;66(3):178-85).

Blood Tests: In a study of biopsy-confirmed 126 celiac patients and 106 controls, the sensitivity of serum antitissue transglutaminase IgA antibodies (IgA-TTG) was 94% and IgA antiendomysial antibodies (IgA-EMA) 89%, the specificity was 99% and 98%, respectively. Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study. Collin P, Kaukinen K, et al. University of Tampere, Finland. Eur J Gastroenterol Hepatol. 2005 Jan;17(1):85-91. Ed: These tests have replaced testing for IgA antigliadin antibodies.

Peripheral Neuropathy: Peripheral neuropathy (PN) is one of the most frequently reported neurologic manifestations associated with celiac disease (CD), a multigenetic, T-cell-mediated autoimmune disorder that results from a loss of tolerance to gluten. Sensory axonal and small fiber sensory polyneuropathies are the most frequently reported PN subtypes. Peripheral Neuropathy and Celiac Disease. Chin RL, Latov N. Cornell University. Curr Treat Options Neurol. 2005 Jan;7(1):43-48.

Carnitine Deficiency: Over 20% of celiac patients are deficient in carnitine. These authors studied 31 patients. Hozyasz K, Czerwinska B. Free and total carnitine levels in patients with celiac disease. Indian J Gastroenterol 2004;23:194-194. 

Neurological Problems More Common: Of 148 CD patients, 18 (12%) had 21 neurological disorders that could not be attributed to any other condition including muscle abnormality (3), epilepsy (3), psychiatric disease (4), peripheral neuropathy (3), cerebrovascular disease (1), myelopathy (1) and Down syndrome (2). J Neurol. 2004 Nov;251(11):1393-7. Ed: The levels of celiac disease in the mentally ill is no higher than in the population in general.  Therefore, unless there are specific symptoms of CD, it is not cost effective to screen for CD.

17% of Chronic Diarrhea were Celiac: In a study of 206 patients with chronic diarrhea, using biopsy and antibodies to alpha-gliadin of class A immunoglobulins (IgA) and tissue transglutaminase, morphologic celiac-specific symptoms were discovered in 17%. Symptoms of the total atrophy were discovered in 13.5%; those of subtotal one were found in 3.4%. The increase of antibody levels to IgA alpha-gliadin and tissue transglutaminase was discovered in all 35 patients. Typical celiac form  occurred in 11%; the latent form in 86%, and the refractory form in 3%.  Eksp Klin Gastroenterol. 2004;(3):31-4, 102-3.

Relatives with CD: Celiac disease occurs more frequently among first-degree relatives of diabetic patients than in the general population. In 240 siblings of diabetic children from 213 families using small bowel biopsy to confirm positive EMA, positive EMA were found in 3.8%, substantially higher than the rate in the healthy children population. High prevalence of coeliac disease in siblings of children with type 1 diabetes. Sumnik Z, Kolouskova S, et al. Prague, Czech Republic. Eur J Pediatr. 2005 Jan;164(1):9-12

Antibody Levels: Antibody levels fall sharply after one month on a gluten-free diet. J Intern Med. 2004 Dec;256(6):519-24. The anti-tTG antibody test can be used to test for dietary compliance, although interviewing patients is usually still better.

Dermatitis Herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a extensive papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet

Dietary Compliance: In 90 European and 40 South Asians studied, the Europeans' assessment of their own strictness to the gluten-free diet correlated with small bowel histological recovery (OR 10.00) and negative endomysial antibodies (OR 34.94). This was not seen in the South Asian patients. For Europeans, factors correlating with compliance with a gluten-free diet were: Coeliac Society membership, understanding food labelling, obtaining sufficient gluten-free products, explanation by a physician, and regular dietetic follow-up. Factors relating to compliance with a gluten-free diet in patients with coeliac disease: comparison of white Caucasian and South Asian patients. Butterworth JR, Banfield LM, et al. Birmingham, UK. Clin Nutr. 2004 Oct;23(5):1127-34.

Stroke 29% Higher in Celiac Disease: In a study of 3,790 adults with celiac disease and 17,925 controls, celiac patients were less likely to have had a diagnosis of hypertension [11% vs. 15%, odds ratio 0.68] or hypercholesterolaemia [3.0% vs. 4.8%, odds ration 0.58] but slightly more likely to have had atrial fibrillation [2.1% vs. 1.7%, odds ratio 1.26]. The hazard ratio for myocardial infarction was 0.85 (not significant), while the hazard ratio for stroke was 1.29 (95% confidence interval: 0.98-1.70), a strong trend almost reaching statistical significance. The effect of a gluten-free diet on cardiovascular risk factors should be determined before any screening programs for celiac disease are instituted. Risk of vascular disease in adults with diagnosed coeliac disease: a population-based study. West J, Logan RF, et al. University of Nottingham, UK. Aliment Pharmacol Ther. 2004 Jul 1;20(1):73-9.

Increased Risk of Death in First Year After Diagnosis: In a study of 4732 people with celiac disease and 23,620 matched controls, 2.8% of celiac patients had at least one malignancy and 5.0% died. The overall hazard ratios were: for any malignancy 1.29, for mortality 1.31, for gastrointestinal cancer 1.85, for breast cancer 0.35, for lung cancer 0.34, and for lymphoproliferative disease 4.80, all statistically significant. The increased risk was primarily in the first year after diagnosis, with the risk for only lymphoproliferative disease remaining raised thereafter. After excluding events in the year after diagnosis, the hazard ratio for malignancy was 1.10 and for mortality was 1.17, giving absolute excess rates of 6 and 17 per 10,000 person years, respectively. Malignancy and mortality in people with coeliac disease: population based cohort study. West J, Logan RF, et al. University of Nottingham, UK. BMJ. 2004 Sep 25;329(7468):716-9.

Cancer Deaths Increased in Adult Celiac Study: In a study of 653 patients with celiac disease, mortality overall was 1.9-fold that of the general population (115 deaths observed, 61.8 expected; p less than 0.0001). The increased mortality was greatest within 1 yr of diagnosis of celiac disease and steadily declined over time with the excess mortality being concentrated at ages 45-54 yr in men and 55-64 yr in women. Of 17 deaths from lymphoproliferative diseases (0.55 expected, p less than 0.001), 8 occurred within 2 yr of diagnosis of celiac disease compared with 8 (0.37 expected, p less than 0.001) occurring greater than 5 yr after diagnosis. Esophageal cancer was certified as the cause of four deaths (0.47 expected, p less than 0.01). In men mortality from all other malignant disease was also increased (15 deaths observed; 6.4 expected, p less than 0.01), but most of these deaths occurred within 5 yr of the diagnosis of celiac disease. There was no deficit in deaths from ischemic heart disease or stroke and the mortality rate in those diagnosed in childhood as having celiac disease was similar to the general population. Mortality in celiac disease. Logan RF, Rifkind EA, et al. University of Nottingham, United Kingdom. Gastroenterology. 1989 Aug;97(2):265-71.

Bread: Special Sourdough OK: Selected sourdough lactobacilli had specialized peptidases capable of hydrolyzing Pro-rich peptides, including the 33-mer peptide, the most potent inducer of gut-derived human T-cell lines in CS patients.  A sourdough made from a mixture of wheat (30%) and nontoxic oat, millet, and buckwheat flours was started with lactobacilli. After 24 h of fermentation, wheat gliadins and low-molecular-mass, alcohol-soluble polypeptides were hydrolyzed almost totally. In a DB test, 13 of the 17 patients showed a marked alteration of intestinal permeability after ingestion of baker's yeast bread. When fed the sourdough bread, the same 13 patients had values for excreted rhamnose and lactulose that did not differ significantly from the baseline values. The other 4 of the 17 CS patients did not respond to gluten after ingesting the baker's yeast or sourdough bread. Sourdough bread made from wheat and nontoxic flours and started with selected lactobacilli is tolerated in celiac sprue patients. Di Cagno R, De Angelis M, et al. University of Bari, Italy. Appl Environ Microbiol. 2004 Feb;70(2):1088-96.

Height in Children with Undiagnosed CD Definitely Impaired: Of 5470 children tested, 54 tested positive for IgA-EMA (1.0%). IgA-EMA were twice as common in girls (odds ratio 2.12). IgA-EMA positive children were shorter and weighed less than those who tested negative for tTG antibody (P < 0.0001 for all comparisons). The loss was equal to about 9 months of growth. 50% of IgA-EMA positive children reported diarrhea compared with 34% of tTG antibody negative (odds ratio 1.96). Only one IgA-EMA positive child had consulted a doctor about diarrhea. There was no overall difference in the number of episodes of diarrhea. Vomiting, abdominal pain, and constipation were not associated. P Bingley et al. BMJ 2/7/04. 5% of short children in a Brazilian study were positive for CS.

tTGA Good Screen, But EMA Still Valuable: Overall, 2,505 tTGA tests were performed: 8.6% were tTGA-positive of which 75% were EMA-negative (group 1) and 25% EMA-positive (group 2.) Of those biopsied, celiac disease was diagnosed in 12% in group 1 and 85% in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA. Positive tissue transglutaminase antibodies with negative endomysial antibodies: low rate of celiac disease. Weiss B, Bujanover Y, et al. Israel. Isr Med Assoc J. 2004 Jan;6(1):9-12.

Children CS Causes Irritability and Tiredness: When compared with children with normal intestinal biopsies, children with celiac disease more often had abdominal distension (odds ratio [OR] = 22.17), thin extremities (OR = 5.89), irritability (OR = 6.50), and tiredness (OR = 15.43). Sweden. J Pediatr Gastroenterol Nutr. 2004 Feb;38(2):181-6.

Refractory celiac disease (RCD) is a rare syndrome with a poor prognosis, defined by malabsorption due to gluten-related enteropathy after initial or subsequent failure of a strict gluten-free diet. Based on intraepithelial T-lymphocyte(IEL) phenotyping, 19 patients were recorded as having RCD type I with normal IELs, or RCD type II with phenotypically immature IELs defined by a lack of characteristic T-cell markers. Clinical improvement was seen in nearly all patients with azathioprine combined with prednisone for 1 year in both groups. Eight of 10 RCD type I patients responded histologically, and complete normalization of villi was seen in four patients. In RCD type II, 6/8 patients developed enteropathy-associated T-cell lymphoma (EATL) and 7/8 patients died. Azathioprine and prednisone combination therapy in refractory coeliac disease. Goerres MS, Meijer JW, et al. Arnhem, The Netherlands. Aliment Pharmacol Ther. 2003 Sep 1;18(5):487-94.

Non-Hodgkin's Lymphoma Risk Increased by CD: In a follow-up of 381 celiac disease patients, 11% had a diagnosis of cancer; 9 were after the diagnosis of celiac disease, 7 were simultaneous (during same month or admission), and 27 were before the diagnosis. Small bowel cancer (SMR 34), esphageal cancer (SMR 12), melanoma (SMR 5) and non-Hodgkin's lymphoma (standardized morbidity ratio (SMR) 9) were all markedly more common. Following the diagnosis of celiac disease, patients were at increased risk of non-Hodgkin's lymphoma only (SMR = 6.2), despite adherence to a gluten-free diet. Risk of malignancy in patients with celiac disease. Green PH, Fleischauer AT, et al. Columbia University. New York. Am J Med. 2003 Aug 15;115(3):191-5. Am J Med. 2003 Aug 15;115(3):191-5.

Fractures Slightly Increased: People with celiac disease are at risk of developing osteoporosis. In a study of 4732 people with celiac disease and 23,620 age- and sex-matched control subjects, the mean age at CD diagnosis was 44 years, and 67% were women. The overall hazard ratio for any fracture was 1.30, for hip fracture was 1.90, and for ulna or radius fracture was 1.77. The absolute difference in the overall fracture rate was 3.20 per 1000 person-years and for hip fracture it was 0.97 per 1000 person-years in those older than 45 years. Fracture risk in people with celiac disease: a population-based cohort study. West J, Logan RF, et al. Queen's Medical Centre, Nottingham, UK. Gastroenterology. 2003 Aug;125(2):429-36.

Osteoporosis May be Risk Factor: In a relatively small study of 266 adults with osteoporosis  and 574 without, celiac disease occurred in 3.4% of people with osteoporosis versus 0.2% without osteoporosis. The authors suggest screening all with osteoporosis for CD. Archives of Internal Medicine 2/05.

Mortality Rate Doubled in Hospitalized CD: Nationwide data on 10,032 Swedish patients hospitalized with celiac disease and surviving at least 12 months were linked with the national mortality register. For all causes of death combined, mortality risks were significantly elevated: 2.0-fold among all patients with celiac disease and 1.4-fold among patients with celiac disease with no other discharge diagnoses at initial hospitalization. Mortality risks were elevated for a wide array of diseases, including non-Hodgkin lymphoma (SMR, 11.4), cancer of the small intestine (SMR, 17.3), autoimmune diseases (including rheumatoid arthritis [SMR, 7.3] and diffuse diseases of connective tissue [SMR, 17.0]), allergic disorders (such as asthma [SMR, 2.8]), inflammatory bowel diseases (including ulcerative colitis and Crohn disease [SMR, 70.9]), diabetes mellitus (SMR, 3.0), disorders of immune deficiency (SMR, 20.9), tuberculosis (SMR, 5.9), pneumonia (SMR, 2.9), and nephritis (SMR, 5.4). Causes of death in patients with celiac disease in a population-based Swedish cohort. Peters U, Askling J, et al. NIH, Bethesda, MD. Arch Intern Med. 2003 Jul 14;163(13):1566-72.

Ancient Wheat May Be Safe: Wheat, rye and barley are toxic in CD from proteins such as gliadins, secalins and hordeins. Agglutination of in vitro cultured human myelogenous leukemia K 562 (S) cells proved to be a suitable model for detection of toxic components of proteins. Five toxic peptides derived from an A-gliadin protein have been found to agglutinate the K 565 (S) cells. Triticum monococcum is a diploid wheat species widely grown during the Bronze Age. Proteins from monococcum are unable to agglutinate the K 562 (S) cells. Genetic improvement of plant for coeliac disease. Pogna NE. Institute for Cereal Research, Rome, Italy. Dig Liver Dis. 2002 Sep;34 Suppl 2:S154-9.

Transglutaminases: Nature's Biological Glues: Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. Deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. Griffin M, Casadio R, Bergamini CM.Nottingham Trent University, U.K. Biochem J. 2002 Dec 1;368(Pt 2):377-96.

Underutilized cereals: The following can be milled into safe flours: amaranth, buckwheat (or kasha), chickpeas (garbanzos), Job's tears (Hato Mugi, Juno's Tears, River Grain), lentils, millet, peas, quinoa, ragi, sorghum, soy, tapioca, teff, corn starch, corn meal, rice, arrowroot, potato, tapioca, and wild rice. To improve the texture of gluten-free baked goods, most cooks use one or more of the following: xanthan gum, guar gum (though this sometimes has a laxative effect), methylcellulose, or a new product called Clear Gel.

Refractory DC: Of the 49 patients referred with non-responsive celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue. Only nine had refractory CD. Mayo Clinic. Am J Gastroenterol. 2002 Aug;97(8):2016-21.

Long-treated adult celiac disease patients in a 10-year Swedish study showed no difference in psychological well-being to population controls, suggesting that signs of depressed mood is no feature of well-treated celiac disease. Dig Liver Dis 2006 Feb 3

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Things to avoid unless certain of their source: Caramel color (infrequently made from barley), Dextrin (usually corn, but may be derived from wheat), Malt or malt flavoring (usually made from barley. Okay if made from corn), Malt vinegar, Modified food starch or modified starch (from unspecified or forbidden source). Avoid beer and malt beverages. When hydrolysed plant protein is clearly indentified in the ingredient list as being from soy, corn or peanut protein (e.g. hyrolysed soy protein) it is safe for people with Celiac Disease. However, when hydrolysed plant protein is made from wheat protein people with celiac disease cannot eat it because they cannot guarantee that it has been completely hydrolysed. So remember, if hydrolysed plant protein is made from wheat, or if the plant source is not identified, don't eat it.