34 Jeffrey Dach MD on Celiac Disease, Gluten Intolerance, the Unsuspected Epidemic

All About Celiac Disease, and Gluten by Jeffrey Dach MD

Fifty three year old Sally McCann came to my office with menopausal symptoms of hot flashes and night sweats.  Sally has trouble sleeping, chronic fatigue, and patchy hair loss.  She has taken anti-anxiety medication (Buspar) for daily anxiety attacks, and Ambien for sleep, both for the past nine years.  Sally is from West Ireland, and has typical features with red hair, green eyes and a fair complexion.  She mentions GI symptoms of “irritable bowel”, i.e. bloating, gas, alternating constipation and diarrhea.  She mentions neurological symptoms of tingling and numbness in her hands and feet.   Sally has been to many doctors over the years and has tried many different treatments, and so far nothing has helped her. Left Image courtesy of Eve Garrison Art Collection.

Examination

Upon examination Sally had a small bald spot on her scalp, loss of outer third of the eyebrows, and brittle cracking nails.  Image at right shows a typical bald spot, called Alopecia Areata caused by Celiac Disease (different patient). Image courtesy of Wikimedia Commons.

Laboratory Findings

Sally’s lab studies showed a microcytic anemia.  Her blood cells were smaller and fewer than normal. This usually indicates Iron deficiency anemia.  Her serum Iron, however was not too low because she has been taking Iron supplements.  Sally informs me that her blood count has always been low and she has been taking Iron supplements for years. 

Sally's blood test also showed Hashimoto's thyroiditis with elevated thyroglobulin and peroxidase antibody levels.

Sally’s blood tests for Celiac Disease were negative (these are antibodies called IgA TTG and EMA).  However, here stool test thorugh EnteroLabs was positive for the TTG antibody in the stool, and she also was positive for the genetic test.  These findings indicated that Sally has intolerance of wheat gluten, also called celiac disease.

I explained that many of her symptoms of peripheral neuropathy (tingling sensations), hair loss, anemia, and anxiety are caused by her inability to tolerate wheat gluten in her diet.  And that all of her symptoms would be resolved on a gluten free diet.
Sally was also started on bioidentical hormones for her menopausal  symptoms, and natural thyroid for her low thyroid Hashimoto's Disease.  Other family members should have genetic screening for celiac as well. 

Treatment Program

The major treatment for Celiac Disease is a Gluten Free Diet.

Sally’s Salivary Cortisol test showed a reversed pattern with low cortisol in the morning and high cortisol at night, explaining her morning fatigue and inability to sleep. The treatment for this is a nutritional supplement called Seriphos, (phosphorylated serine ) which resets the biological cortisol clock and the pattern returns to normal in about 6 weeks.
 
To address adrenal fatigue, an adrenal vitamin program was also started which includes Vitamin C, B5, biotin, and adrenal herbs such as ashwaganda and licorice.

For sleep, Sally was started on melatonin and 5-HTP which replaces the Ambien.  And to increase morning energy, Sally was started on D-ribose, L-L-Carnitine and Co-enzyme Q-10.

For the peripheral neuropathy, Sally is given B12, R-Alpha Lipoic Acid and  and Benfotiamine, a lipid soluble form of thiamine.

A Successful Outcome
 
Six weeks after starting a Gluten free diet, Sally says she is much better.  The neuropathy symptoms of tingling and numbness in the hands and feet have improved, she has more energy, sleeping better, and her hot flashes and night sweats are gone.  The hair loss is better as well. In short she is a happy camper.

Celiac Disease is commonly associated with Hashimoto's Thyroid Disease, Adrenal disorders, Osteoporosis, Alopecia areata, chronic abdominal pain, Skin disorder called Dermatifromis Herpetica, Vitamin K and B12 deficiency, Iron deficiency Anemia, Peripheral Neuropathy, and other neurological disorders.  It tends to run in families and has a genetic component.

Celiac Disease Testing

We do not use blood testing for celiac disease, finding it rarely useful.  Instead, we have found the stool TTG antibody tests offered by EnteroLabs to be more useful.

Jeffrey Dach  MD
http://www.drdach.com
www.jeffreydachmd.com
www.naturalmedicine101.com
www.truemedmd.com

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The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician -- patient relationship.  Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur Finally, the material produced by myself may be reproduced for personal use, provided that appropriate credit is given; but this material may not be reprinted or reproduced in any format for any other purpose.

References:

Video on Celiac Disease

http://thenewsroom.com/details/1872868
Video from Mayo Clinic on Celiac Disease, Gluten Free Diet

Review Articles

http://www.aafp.org/afp/980301ap/pruessn.html
Detecting Celiac Disease in Your Patients. HAROLD T. PRUESSNER, M.D., University of Texas Medical School at Houston Am Fam Physician Mar 1998. excellent review in American Academy of Family Physicians.

Celiac disease may be greatly underdiagnosed and is relatively common in this country. Approximately 95 percent of patients with celiac disease have a particular type of HLA DQ alpha and beta chain encoded by two genes, HLA-DQA1 0501 and HLA-DQB1 0201
Viral exposures may trigger an immunologic response in persons genetically susceptible to celiac disease; this occurs with adenovirus type 12, which shares a sequence of eight to 12 amino acids with the toxic gliadin fraction.

Causes of Delay in Diagnosis

Recognizing celiac disease on the basis of the various manifestations of the disorder is difficult. In a study20 of 228 patients with adult-onset celiac disease, it was found that 42 were diagnosed at age 60 or later. Seven patients with dermatitis herpetiformis were excluded, leaving 35 patients in the analysis. Fifteen of the 35 patients had been seen--with unexplained symptoms and abnormal blood tests--for an average of 28 years by their family physicians or in hospital outpatient departments before the diagnosis of celiac disease was made.

Symptoms and Prevalence of Celiac Disease

http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/
NIH. How common is celiac disease? Data on the prevalence of celiac disease is spotty.
In Italy about 1 in 250 people, and in Ireland about 1 in 300 people, have celiac disease. Recent studies have shown that it may be more common in Africa, South America, and Asia than previously believed.  Until recently, celiac disease was thought to be uncommon in the United States. However, studies have shown that celiac disease is very common. Recent findings estimate about 2 million people in the
United States have celiac disease, or about 1 in 133 people.  Among people who have a first-degree relative diagnosed with celiac disease, as many as 1 in 22 people may have the disease.

Symptoms of celiac disease may include one or more of the following:

• gas
• recurring abdominal bloating and pain
• chronic diarrhea
• constipation
• pale, foul-smelling, or fatty stool
• weight loss/weight gain
• fatigue
• unexplained anemia (a low count of red blood cells causing fatigue)
• bone or joint pain
• osteoporosis, osteopenia
• behavioral changes
• tingling numbness in the legs (from nerve damage)
• muscle cramps
• seizures
• missed menstrual periods (often because of excessive weight loss)
• infertility, recurrent miscarriage
• delayed growth
• failure to thrive in infants
• pale sores inside the mouth, called aphthous ulcers
• tooth discoloration or loss of enamel
• itchy skin rash called dermatitis herpetiformis

http://www.ncbi.nlm.nih.gov/pubmed/16772832
Eur J Gastroenterol Hepatol. 2006 Jul;18(7):747-54. Links
Health-related quality of life in adult coeliac disease in Germany: results of a national survey.

Even while on a diet, health-related quality of life (HRQOL) may be decreased in people with coeliac disease. Some have persisting digestive symptoms or dermatitis herpetiformis, mouth ulcers, osteoporosis and fractures. Symptoms suggestive of irritable bowel syndrome may be present, and there is an increased rate of anxiety, fatigue, dyspepsia and musculoskeletal pain.[55]

Screening for Celiac Disease, In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends screening for coeliac disease in patients with newly diagnosed

1) chronic fatigue syndrome
2) irritable bowel syndrome
3 ) autoimmune thyroid disease. Hashimotos

http://www.celiacdisease.net/assets/pdf/CDCFactSheetsAntibodyScreening3.pdf
University of Chicago CeliacDisease Center 773.702.7593 www.CeliacDisease.net.

Screening Test:  anti-tissue transglutaminase (tTG-IgA)A screening test is commonly used when an individual is in a risk group for celiac disease, whether or not he/she has symptoms. This test is usually the one offered for celiac screening events, as it is the most sensitive test available.

Other Tests: • Total Serum IgA to test for IgA deficiency (this health condition can affect accuracy of antibody test)• Anti-endomysial antibody test (EMA-IgA) EMA-IgA are very specific for celiac disease but they are not as sensitive as the tTG-IgA.•

HLA-DQ2 and HLA-DQ8 gene tests for celiac disease The “gene tests” are not antibodies: they can be used to exclude celiac disease (if negative) in doubtful cases NOTE: Anti-gliadin Antibodies (AGA-IgG and AGA-IgA) are no longer used to test for celiac disease due to a low level of accuracy http://www.celiaccenter.org/faq.asp

What are the recommended blood tests to diagnose CD?  There is a particular series of blood tests called the ‘Celiac Panel”. These tests measure your immune system’s response to gluten in the food you eat.

tTG-IgA or tissue transglutaminase-IgA
AGA-IgG or Antigliadin IgG
AGA-IgA or Antigliadin IGA
Total IGA

The presence of tTG antibodies is highly suggestive of CD, while AGA can be elevated also in cases of wheat allergy. 

How accurate are the celiac blood tests?

The current diagnostic tests for CD are very accurate, particularly when tTG and anti-endomysial antibodies are elevated. The isolated presence of anti-gliadin antibodies does not necessarily imply that the subject is affected by CD, with the exception of children under the age 2 in which tTG and EMA may not be present.

Are the villi permanently damaged in a patient with Celiac Disease and how long does it take for the villi to return to normal?

The villi are not permanently damaged. The intestine is an organ, which renews itself every three days. Therefore, if the damage is exclusively due to CD, the villi will be reformed once on a gluten-free diet. The time for the villa to return to normal varies between individuals.

What is the meaning of HLA DQ2/DQ8?

As an autoimmune disease, CD is the consequence of the interplay between genes and the environment (gluten). We don’t know all the necessary genes to develop CD; however, HLA DQ2 and/or DQ8 are absolutely necessary to develop the disease. Since 1/3 of the general population also have these genes, the presence of DQ2 or DQ8 does not imply that the person will develop CD, rather, that they have a genetic compatibility with CD. Conversely, the absence of DQ2/DQ8 almost certainly rules out CD.
Fat soluble vitamins malabsorbed : panel A, D, E and K

Pattern of Presentation of Celiac Disease

http://adc.bmj.com/cgi/content/abstract/91/12/969
The changing clinical presentation of coeliac disease  M Ravikumara, D P Tuthill, H R Jenkins Department of Paediatric Gastroenterology, University Hospital of Wales, Cardiff, UK

Methods: A 21-year review of prospectively recorded data on the mode of presentation of biopsy confirmed coeliac disease in a single regional centre. Presenting features over the past 5 years were compared with those of the previous 16 years. Between 1983 and 1989 (inclusive), no serological testing was undertaken; between 1990 and 1998, antigliadin antibody was used with occasional use of antiendomysial antibody and antireticulin antibody. From 1999 onwards, anti-tissue transglutaminase was used.

http://www.nutritionj.com/content/5/1/24
Patterns of clinical presentation of adult coeliac disease in a rural setting. Sián Jones , Charles D'Souza  and Nadim Y Haboubi Nutrition Journal 2006, 5:24doi:10.1186/1475-2891-5-24

Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia.

With the introduction of serologic tests for coeliac disease, disease variants have been recognised which present with atypical features such as fatigue, asymptomatic iron deficiency, decreased bone density and dyspepsia without the classic malabsorption syndrome. Other presentations could include isolated hypoalbuminaemia, elevated aminotransferase levels (transaminitis), microscopic colitis, symptoms of irritable bowel syndrome, recurrent aphthous stomatitis, infertility, neurologic symptoms such as peripheral neuropathy, ataxia and epilepsy with posterior cerebral calcification. The findings of this study suggest that patients presenting to their general practitioner with unexplained iron deficiency anaemia, unexplained fatigue or generalised abdominal pain should undergo serological testing for coeliac disease.

Celiac Disease Gluten Free Diets

Gluten Free Diets

http://www.healthsystem.virginia.edu/internet/digestive-health/nutritionarticles/dennisarticleapril.pdf
Going Gluten-Free: A Primer for Clinicians PRACTICAL GASTROENTEROLOGY, 2004

One Mom's Experence with Celiac Disease
http://sortacrunchy.typepad.com/sortacrunchy/2008/02/qa-whats-the-de.html
Sorta Crunchy One moms experience with Son having celiac disease, gluten free diet.

News about Gluten Free Restaurants

http://biz.yahoo.com/prnews/080227/law057.html?.v=101
Gluten-Free Restaurant Recommendations Double in Less Than 3 Months. Wednesday February 27, Glutenfreeonthego.com Answers Exploding Demand from Celiacs / Coeliacs, Gluten-Free Guests & Food Allergic Customers

http://www.vaildaily.com/article/20080226/AE/685641038
The challenge of cooking gluten-free, David Hagedorn, L.A. Times-Washington Post News Service Vail CO, Colorado February 26, 2008

Celiac.com  Web Site  http://www.celiac.com/  Celiac Com Gluten Free Diets etc.

http://www.celiac.com/articles/21521/1/How-Early-Can-Celiac-Disease-Be-Diagnosed/Page1.htmlHow Early Can Celiac Disease Be Diagnosed? Rodney Ford

http://www.doctorgluten.com/cms/ Rodney Ford Web Site Celiac Disease

http://www.doctorgluten.com/cms/index.php?option=com_content&task=view&id=111&Itemid=162
Rodney Ford. To diagnose coeliac disease (that is when you get gut tissue damage), the first step is to look for evidence of gut damage by blood tests.  These "tissue damage" tests are called: tissue transglutaminase (tTG) or endomesial antibodies (EMA).  If these are positive, then you should have an endoscopy (also called a small bowel biopsy) to confirm the diagnosis.  If you do have coeliac disease, then you are committed to a lifelong gluten-free diet.  So it is very important to make a firm diagnosis.

To diagnose gluten-sensitivity (reactions to gluten without the gut damage).  The blood tests that you need are the IgG-gliadin and the IgA-gliadin tests.  A positive test shows that you are experiencing an immune reaction to gluten.  Most gluten-sensitive people have a high IgG-gliadin test.
We prefer the test kits form Inova Diagnostics

Incidence of Celiac Disease, Epidemiology

http://www.celiachealth.org/pdf/epidem.pdf
Slide show of Celiac Disease epidemiology

http://www.doctorgluten.com/cms/index.php?option=com_
mamblog&task=show&action=view&id=232&Itemid=377
Doctor Gluten. When Dr Alessio Fasano (Medical Director,  University Of Maryland, Center for Celiac Research, http://www.celiaccenter.org/mission.asp ) was asked how many of the population were just gluten intolerant. His reported to reply a staggering “35%.(1 in 3)”  This is in line with Ken Fine who also has data to show that about a third of all people react in some way to gluten.

I have been more cautious, claiming that at least 10% (one in ten) of the population is gluten-sensitive.  For a fact, about 1% (one in a hundred) of the population has celiac disease.So how common is the gluten problem? Very common!

http://www.biomedcentral.com/1471-2172/9/6
Research article, Secretion of celiac disease autoantibodies after in vitro gliadin challenge is dependent on small-bowel mucosal transglutaminase 2-specific IgA deposits. Satumarja M Stenman , Katri Lindfors , Ilma R Korponay-Szabo , Olli Lohi , Paivi Saavalainen , Jukka Partanen , Katri Haimila , Herbert Wieser , Markku Maki  and Katri Kaukinen  BMC Immunology 2008, 9:6doi:10.1186/1471-2172-9-6. Published: 29 February 2008

Review Articles on Celiac Disease

http://www.ajcn.org/cgi/content/full/69/3/354
American Journal of Clinical Nutrition, Vol. 69, No. 3, 354-365, March 1999
Review Article  The widening spectrum of celiac disease1,2 Joseph A Murray

Deficiencies of the fat-soluble vitamins D, E, A, and K; iron; folic acid; and calcium are also common. The deleterious proteins are gliadins (wheat), hordeins (barley), secalins (rye), and possibly avidins (oats)

These atypical modes of presentation include deficiencies of single micronutrients; nonspecific gastrointestinal complaints such as bloating, abdominal pain, diarrhea, constipation, flatulence, secondary lactose intolerance, and dyspepsia; and nongastrointestinal complaints such as fatigue, depression, arthralgia, milk intolerance, osteomalacia or osteoporosis, and iron deficiency anemia (11, 48–50). Iron deficiency anemia can occur with or without heme-positive stool (51).

Psychiatric referral is also common before diagnosis; often, patients require a great degree of determination to persist in seeking an organic cause for their symptoms

Celiac disease is particularly common in patients with type 1 diabetes, thyroid disease, Addison disease, osteopenic bone, Down syndrome, and rheumatologic complaints

Celiac disease should be considered in anyone with conditions associated with a high risk of the disease, such as type 1 diabetes, autoimmune thyroid disease, T cell lymphoma, osteoporosis, and infertility, and in those with a family history of celiac disease or dermatitis herpetiformis

Dermatitis herpetiformis is an extremely itchy, bullous skin rash that affects the extensor surfaces of the limbs, trunk, and scalp.

Several noninvasive tests of malabsorption are used to decide whether a biopsy should be performed. These include tests of deficiency states, such as measurements of hemoglobin and red cell indexes, carotene, vitamin D, prothrombin time, and iron and folate concentrations; tests of absorption, including the D-xylose test; qualitative or quantitative fecal fat tests; and contrast radiography. These tests may be important for identifying malabsorption but have variable sensitivity for celiac disease. For example, fecal fat measurements may be normal in 30% of persons with celiac disease. Many patients with celiac disease also have normal concentrations of hemoglobin and vitamins, which may be due to the widespread use of supplements.

http://www.aafp.org/afp/20021215/2259.html
Gluten-Sensitive Enteropathy (Celiac Disease): More Common Than You Think
DAVID A. NELSEN, JR., M.D., M.S., University of Arkansas for Medical Sciences, Little Rock, Arkansas 1: Am Fam Physician. 2002 Dec 15;66(12):2259-66 Excellent review clinical

http://www.gastrojournal.org/article/PIIS0016508501701618/fulltext
Volume 120, Issue 6, Pages 1522-1525 (May 2001)
American Gastroenterological Association medical position statement: Celiac sprue. Official recommendations of the American Gastroenterological Association (AGA) on Celiac Sprue.

http://consensus.nih.gov/2004/2004CeliacDisease118main.htm
1: NIH Consens State Sci Statements. 2004 Jun 28-30;21(1):1-23.
NIH Consensus Development Conference on Celiac Disease.

Alopecia Areata

http://www.ncbi.nlm.nih.gov/pubmed/7557104
Gastroenterology. 1995 Oct;109(4):1333-7. Links
Celiac disease and alopecia areata: report of a new association.
Corazza GR, Andreani ML, Venturo N, Bernardi M, Tosti A, Gasbarrini G. Department of Internal Medicine, University of L'Aquila, Italy.

Celiac disease is frequently associated with other autoimmune disorders but has never been reported in association with alopecia areata. In a routine clinical practice, 3 patients with such an association were observed. In one of the patients, celiac disease was diagnosed after the occurrence of malabsorption symptoms. In the youngest patient, a 14-year-old boy, gluten-free diet resulted in complete regrowth of scalp and body hair. A prospective screening program for celiac disease using antigliadin and antiendomysial antibodies was therefore set up in 256 consecutive outpatients with alopecia areata. Three patients, all completely asymptomatic for intestinal diseases, were found to be positive and underwent biopsy. Histological analysis showed a flat intestinal mucosa consistent with the diagnosis of celiac disease. The results show that alopecia areata may constitute the only clinical manifestation of celiac disease and that the association between these two conditions is a real one because the observed frequency of association is much greater than can be expected by chance. It is suggested that antigliadin and antiendomysial antibodies should be included in the work-up of patients with alopecia areata.

Celiac Disease and Osteoporosis

http://archinte.ama-assn.org/cgi/content/full/165/4/393
Increased Prevalence of Celiac Disease and Need for Routine Screening Among Patients With Osteoporosis

William F. Stenson, MD; Rodney Newberry, MD; Robin Lorenz, MD, PhD; Christine Baldus, RN, BSN; Roberto Civitelli, MD Arch Intern Med. 2005;165:393-399.

Individuals also received serologic testing for IgG antigliadin, IgA antigliadin, IgA antitissue transglutaminase (anti-TTG), and IgA antiendomysial antibody (anti-EMA). Reagents for the antigliadin and anti-TTG tests were from INOVA Diagnostics, Inc (San Diego, Calif); reagents for anti-EMA were from Binding Site (Birmingham, England).

Cardiomyopathy and Celiac Disease

http://www.ncbi.nlm.nih.gov/pubmed/15887437
Mayo Clin Proc. 2005 May;80(5):674-6. Cardiomyopathy associated with celiac disease.Goel NK, McBane RD, Kamath PS.Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.

Celiac disease or celiac sprue is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon, celiac disease may be present in up to 1% of the general population. Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, with early diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may be completely reversible.

Myopathy and Celiac Disease

http://www.ncbi.nlm.nih.gov/pubmed/16967485
Muscle Nerve. 2007 Jan;35(1):49-54,
Celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathy. Selva-O'Callaghan A, Casellas F, de Torres I, Palou E, Grau-Junyent JM, Vilardell-Tarrés M.

Celiac disease is usually associated with autoimmune disorders and has occasionally been reported in patients with inflammatory myopathies. Our aim was to determine the presence of celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathies and to investigate their relationship. Serum antigliadin, anti-tissue transglutaminase, and antiendomysial antibodies were determined in 51 patients with inflammatory myopathies. HLA-DQ2 and -DQ8 alleles were studied to assess their complementary diagnostic value. Jejunal biopsy was performed in patients with moderate to high levels of antigliadin antibodies. Patients with jejunal histology consistent with celiac disease initiated a gluten-free diet. Seventeen patients (31%) were positive for antigliadin antibodies, which were significantly more frequent in patients with inclusion-body myositis than dermatomyositis (P < 0.001). Positive status to HLA-DQ2 and/or -DQ8 did not differ between antigliadin-positive (75% and 12.5%) or -negative (60% and 15%) patients. Three of five jejunal biopsies were diagnostic for celiac disease with histological normalization after a gluten-free diet. Thus, celiac disease is more prevalent in patients with inflammatory myopathies than in the general population. Positive status to HLA-DQ2 allele, which is known to be more frequent in patients with inflammatory myopathies, could explain the high prevalence of antigliadin antibodies in this population. The diagnostic value of HLA-DQ2 or -DQ8 haplotypes to detect celiac disease in patients with inflammatory myopathy is limited.

Sarcoidosis and Celiac Disease

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1B-49KJMHH-2M0&_user=10&_rdoc=1&_fmt=&_orig=search&_
sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_
userid=10&md5=6e0ae5fae10b9ea418047ed3ccca7bba

SARCOIDOSIS AND COELIAC DISEASE: AN ASSOCIATION?  Science Volume 324, Issue 8393, 7 July 1984, Pages 13-15. J. G. Douglas, R. F. A. Logan1, J. Gillon, I. W. B. Grant and G. K.

An association between sarcoidosis and coeliac disease is suggested by the occurrence of both diseases in 5 patients. In 3 cases the gastrointestinal symptoms of coeliac disease preceded those of sarcoidosis and in the other 2 patients symptoms of both diseases appeared at the same time.

http://www.ncbi.nlm.nih.gov/pubmed/17934825

Dig Dis Sci. 2007 Oct 13 Sarcoidosis in Patients with Celiac Disease.Hwang E, McBride R, Neugut AI, Green PH.Department of Medicine, Columbia University Medical Center, 180 Fort Washington Avenue, Room 956, New York, NY, 10032, USA,

Purpose Several case reports and European studies have suggested an association between sarcoidosis and celiac disease; however, they have been inconsistent. We therefore analyzed a large cohort of celiac-disease patients to assess this association. Methods An anonymized database of patients with celiac disease was reviewed to determine the number of patients with sarcoidosis. Age- and gender-adjusted standardized morbidity ratios with corresponding 95% confidence intervals (CI) were calculated by comparing results to US-population-derived prevalence data. Results Ten patients were found to have a comorbid diagnosis of sarcoidosis, representing an age- and gender-adjusted standardized morbidity ratio of 36.8 (95% CI 26.7-50.9). Conclusions In this cohort of patients with celiac disease, there was a significantly increased risk of sarcoidosis when compared with the American white population. This further strengthens prior associations that have been made suggesting a shared mechanism behind the etiologies of celiac disease and sarcoidosis.

Prevalence and Epidemiology of Celiac Disease
http://www.eurojgh.com/pt/re/ejgh/abstract.00042737-200305000-00003.htm

High prevalence of coeliac disease in apparently healthy Iranian blood donors. European Journal of Gastroenterology & Hepatology. 15(5):475-478, May 2003. Shahbazkhani, Bijan a; Malekzadeh, Reza a; Sotoudeh, Masoud a; Moghadam, Ketaion Fayaz a; Farhadi, Mohammad a; Ansari, Reza a; Elahyfar, Amin a; Rostami, Kamran b

Abstract:  Background/objective: Studies about the prevalence of coeliac disease in countries in western Asia are scarce and there is no study on the prevalence of coeliac disease in Iran. The aim of this study was to determine the prevalence of coeliac in healthy, Iranian, blood donors.

Study design and methods: Blood samples were obtained from 2000 apparently healthy blood donors (1580 males, 420 females; mean age 35.5 years, range 18-65 years) at the Tehran Blood Donation Centre during a 4 month period from November 1998 through February 1999. Total serum IgA was measured in all donors, and IgA deficient cases were excluded. All cases were analysed for IgA anti-gliadin (AGA) by an ELISA test and those with positive results were tested for IgA anti-endomysium antibody (EMA) using immunofluorescence. All donors who had a positive serology for both AGA and EMA underwent small intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria (UEGW 2001).

Results: Forty-nine cases showed positive IgA AGA (38 males and 11 females, mean age 38.6 years). Of the 49 AGA positive cases 12 were EMA positive. All subjects with positive serology (both AGA and EMA) were found to have small bowel biopsies compatible with gluten sensitive enteropathy. Three of 12 had Marsh I, 4/12 Marsh II and 5/12 showed a Marsh IIIa lesion.

Conclusion: The minimum prevalence of gluten sensitivity among apparently healthy urban Iranian blood donors is 1/166. Further epidemiological studies in adults from the general population and in high risk groups seems indicated.

Screening and Detection, LAb Testing  of Celiac Disease

http://www.inovadx.com/Posters/GLIADIN%20PEPTIDE%20POSTER%202005.pdf

http://www.celiac.com/articles/57/1/Interpretation-of-Celiac-Disease-Blood-Test-Results/Page1.html

INOVA Diagnostics, Inc., Interpretation of Celiac Disease Blood Test Results. The following detailed explanation of serological tests for celiac disease was written by Tom Ryan, Technical Service Specialist, INOVA Diagnostics, Inc.

My personal feeling is that the minimum is 2 slices of bread per day for 6 weeks to get an accurate test IgG anti-gliadin antibodies are more sensitive but are less specific markers for disease compared with IgA class antibodies. IgA anti-gliadin antibodies are less sensitive but are more specific. A sensitive testing protocol includes testing for both IgA and IgG anti-gliadin antibodies since a significant portion of celiac patients (approx. 2-5%) are IgA deficient. This combined IgA and IgG anti-gliadin antibody assay has an overall sensitivity of 95% with a specificity of 90%. The type of test used to detect the anti-gliadin antibodies is called an ELISA.

Endomysial Antibodies: IgA class anti-endomysial antibodies (AEA) are very specific, occurring only in celiac disease and DH (Dermatiformis Herpeticus). In summary, the tTG ELISA is measuring the same thing that the endomysial IFA is measuring but with a method that is more sensitive and specific and not subject to interpretation.

http://cas2.questdiagnostics.com/scripts/webdos.wls?MGWLPN=QDCIAP22&wlapp=DOS&SearchString=celiac
&auto=false&tmsearch=Search&tmradio=alias&SITE=9&SearchString2
Quest Lab test Panel  for Celiac Disease.

http://www.blackwell-synergy.com/doi/full/10.1046/j.1365-2796.2001.00891.x
Screening for adult coeliac disease – which serological marker(s) to use? J Intern Med 2001; 250: 241–248.

Design. In a population-based cross-sectional study we compared the use of antigliadin antibodies (AGA) of isotypes IgA and IgG, antiendomysial antibodies (AEA) of isotype IgA and antitransglutaminase antibodies (ATGA) of isotype IgA for detecting coeliac disease amongst adults.

Setting. Northern Sweden. Subjects. A total of 1850 of 2500 (74%) invited adults (aged 25–74 years) who were randomly selected from the population register after stratification for age and sex. Main outcome measures. The sensitivity, specificity and predictive values of the AGA, ATGA and AEA tests.

Results. Nine cases of biopsy proven, previously undiagnosed coeliac disease were detected by screening. The sensitivity of both ATGA and AEA was 100% whilst AGA IgA and IgG both had a sensitivity of 89%. The AEA test had a specificity of 100% whereas the specificities of the ATGA, AGA IgA and IgG tests were 97, 96 and 78%, respectively. The positive predictive value for the AEA test was 100%, whereas it was considerably lower for the other tests (ATGA > AGA IgA > AGA IgG), with further decreases for all tests when shifting from a clinical to a screening situation.

Conclusions. When screening for coeliac disease we suggest a serial testing approach, i.e. an initial ATGA test and, when positive, followed by an AEA test, provided that IgA deficiency has been excluded. However, assessment of the small intestinal mucosal morphology is still required to ascertain the diagnosis.

ATGA : antitransglutaminase antibodies (ATGA) of isotype IgA for detecting coeliac disease amongst adults.

http://www.blackwell-synergy.com/doi/full/10.1046/j.1365-2796.2001.00793.x
Identification of a new coeliac disease subgroup: antiendomysial and anti-transglutaminase antibodies of IgG class in the absence of selective IgA deficiency. J Intern Med 2001; 249: 181–188. Picarelli A, Di Tola M, Sabbatella L, Mastracchio A, Trecca A, Gabrielli F, Di Cello T, Anania MC, Torsoli A

Conclusions. In this study, we observed a group of CD patients who were EMA IgG1-positive even in the absence of EMA IgA positivity and IgA deficiency. The diagnosis was based on the finding of the gluten-dependent clinical and histological features typical of CD. Data emerging from the present investigation thus suggest that the prevalence of CD should be reassessed and that the determination of EMA IgG1 could offer a new tool in the diagnostic armamentarium of CD.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2001.03754.x
Radioimmunoassay to detect antitransglutaminase autoantibodies is the most sensitive and specific screening method for celiac disease

Objective: The aim of this study was to establish the most sensitive and specific screening method for celiac disease. We tested three methods based on different principles, which all detect autoantibodies against the same antigen (tissue transglutaminase).

Methods: Sixty-two celiac children at the first biopsy (group 1), 78 celiac children on a gluten-free diet (group 2), 14 celiac children on a gluten-challenge (group 3), and 56 controls with a normal duodenal mucosa (group 4) were studied. The methods used were: 1) radioimmunoprecipitation assay using recombinant tissue transglutaminase (RIA); 2) commercial enzyme immunoassay using guinea pig tissue transglutaminase (ELISA); and 3) indirect immunofluorescence method for detection of antiendomysium antibodies (IF-EMA).

Results: RIA antitransglutaminase autoantibodies were detected in 100% of group 1, 43.6% of group 2, 100% of group 3, and none of the control subjects. ELISA antitransglutaminase autoantibodies were detected in 90.3% of group 1, 9% of group 2, 78.6% of group 3, and in none of the control subjects. IF-EMA were detected in 95.2% of group 1, 11.5% of group 2, 92.3% of group 3, and 1.8% of the controls.

Conclusions: Our results demonstrate a very high sensitivity and specificity of the RIA method to detect antitransglutaminase autoantibodies in comparison to ELISA and IF-EMA assays. We can explain this finding with the use of human recombinant antigen and the increased capacity of the RIA method to detect low titers of autoantibodies. If our data are confirmed by studies on larger series, tissue transglutaminase RIA could be proposed as the best screening method for celiac patients.

http://www.ncbi.nlm.nih.gov/pubmed/17355413
Am J Gastroenterol. 2007 Jul;102(7):1454-60. Detection of Celiac disease in primary care: a multicenter case-finding study in North America. Catassi C, Kryszak D, Louis-Jacques O, Duerksen DR, Hill I, Crowe SE, Brown AR, Procaccini NJ, Wonderly BA, Hartley P, Moreci J, Bennett N, Horvath K, Burk M, Fasano A. Mucosal Biology Research Center and Division of Pediatric Gastroenterology and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

BACKGROUND: Celiac disease (CD) is one of the most common lifelong disorders in western countries. However, most cases remain currently undiagnosed in North America, mostly due to poor awareness of CD by primary care physicians. OBJECTIVES: The aims of this study were (a) to determine whether an active case-finding strategy in primary care could increase the frequency of CD diagnosis and (b) to determine the most common clinical presentations of the condition. METHODS:This was a multicenter, prospective study involving adult subjects during the years 2002-2004, attending one of the participating practices. All individuals with symptoms or conditions known to be associated with CD were tested for immunoglobulin A anti-transglutaminase (tTG) antibodies, and those with elevated anti-tTG were subsequently tested for IgA antiendomysial antibodies (EMA). All subjects who were positive for EMA were advised to undergo an intestinal biopsy and HLA typing.

RESULTS: The study group included 737 women and 239 men, with a median age of 54.3 yr. A positive anti-tTG test was found in 30 out of 976 investigated subjects (3.07%, 95% CI 1.98-4.16). CD was diagnosed in 22 patients (18 women, 4 men). The most frequent reasons for CD screening in these 22 cases were bloating (12/22), thyroid disease (11/22), irritable bowel syndrome (7/22), unexplained chronic diarrhea (6/22), chronic fatigue (5/22), and constipation (4/22).

The prevalence of CD in the serologically screened sample was 2.25% (95% CI 1.32-3.18). The diagnostic rate was low at baseline (0.27 cases per thousand visits, 95% CI 0.13-0.41) and significantly increased to 11.6 per thousand visits (95% CI 6.8-16.4, P < 0.001) following active screening implementation. CONCLUSIONS: This study demonstrates that an active case-finding strategy in the primary care setting is an effective means to improve the diagnostic rate of CD in North America.

Townsend Letter

http://findarticles.com/p/articles/mi_m0ISW/is_2002_Dec/ai_94538644/pg_2 
Gluten intolerance: a paradigm of an epidemic Townsend Letter for Doctors and Patients,  Dec, 2002  by Stacy Astor Shaul

Other diagnostic tests which might be helpful in identifying gluten intolerance, is a urinary peptide for gliadorphin/caseomorphin test from The Great Plains Laboratory. This test measures the peptides from incompletely broken down pieces of protein from gluten and casein.

Neuropathy and Neurological Disorders and Celiac Disease

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WFX-4FVC7DW-R&_user=10&_
rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_
version=1&_urlVersion=0&_userid=10&md5=c85f5245bad24700b3b13794e13cf125

Neurologic presentation of celiac disease. Khalafalla O. Bushara,  Neurology Department, Minneapolis VA Medical Center and University of Minnesota, Minneapolis, Minnesota Gastroenterology Volume 128, Issue 4, Supplement 1, April 2005, Pages S92-S97

http://pediatrics.aappublications.org/cgi/content/full/113/6/1672
PEDIATRICS Vol. 113 No. 6 June 2004, pp. 1672-1676. Range of Neurologic Disorders in Patients With Celiac Disease Nathanel Zelnik, MD, Avi Pacht, MD, Raid Obeid, MD and Aaron Lerner, MD

http://archneur.ama-assn.org/cgi/content/full/62/10/1574
Small-Fiber Neuropathy/Neuronopathy Associated With Celiac Disease Skin Biopsy Findings

Thomas H. Brannagan III, MD; Arthur P. Hays, MD; Steven S. Chin, MD, PhD; Howard W. Sander, MD; Russell L. Chin, MD; Paul Magda, DO; Peter H. R. Green, MD; Norman Latov, MD, PhD Arch Neurol. 2005;62:1574-1578.

All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non–length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet.

Conclusions  Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non–length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.

http://jnnp.bmj.com/cgi/content/abstract/76/7/1028
Journal of Neurology Neurosurgery and Psychiatry 2005;76:1028-1030 Gluten sensitivity and neuromyelitis optica: two case reports S Jacob1, M Zarei1, A Kenton2, H Allroggen2

Multiple Sclerosis and Gluten

http://www.ncbi.nlm.nih.gov/pubmed/15355487
Acta Neurol Scand. 2004 Oct;110(4):239-41. IgA antibodies against gliadin and gluten in multiple sclerosis. Reichelt KL, Jensen D. Institute of Pediatric Research, University of Oslo, Oslo, Norway.

BACKGROUND: Multiple changes in antibodies against various antigens are found in multiple sclerosis (MS). OBJECTIVE: We wanted to measure immunoglobulin A (IgA) antibodies to some common food antigens in MS and also IgG against gliadin and gluten. METHODS: The IgA antibodies were measured in serum against gluten, gliadin, lactoglobulin, lactalbumin, casein and ovalbumin in patients with MS and controls using ELISA technique. IgG was likewise measured for gluten and gliadin. RESULTS: Highly significant increases compared with controls were found for IgA and IgG antibodies against gliadin and gluten. IgA antibodies against casein were significantly increased. Anti-endomycium and anti-transglutaminase antibodies were negative. CONCLUSIONS: The data presented indicate that there may be a possible moderately increased uptake of some specific proteins from the gut in MS compared with controls.

http://www.ncbi.nlm.nih.gov/pubmed/17537569
Clin Neurol Neurosurg. 2007 Oct;109(8):651-3. Epub 2007 May 29. Multiple sclerosis and gluten sensitivity.Borhani Haghighi A, Ansari N, Mokhtari M, Geramizadeh B, Lankarani KB.
Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran.

OBJECTIVE: To compare the frequency of gluten sensitivity in patients with multiple sclerosis (MS) and healthy controls. PATIENTS AND METHODS: The patients were 161 clinically definite MS patients who referred to neurology outpatient clinic of Nemazee Hospital, Shiraz, south of Iran from March 2004 to October 2005. IgG and IgA antigliadin antibodies were measured by enzyme immuno assay (EIA) method. The test of IgA antitranstissue glutaminase (tTG) and duodenal biopsy were carried out in patients with either IgA or IgG AGA positive sera. Antigliadin antibodies were also measured for 166 age and sex matched control group. RESULTS: Neither IgG nor IgA antigliadin antibodies showed significant differences between MS patients and controls. Anti-tTG antibody and histopathologic studies were negative in all patients with positive IgG or IgA antigliadin antibodies results. Mean values of IgG and IgA antigliadin antibodies in MS patients with different sex, age, course, and functional systems involvement were not significantly different. CONCLUSION: Gluten sensitivity is not associated with MS in Iran.

http://www.direct-ms.org/pdf/NutritionMS/Gluten%20sensitivity%20and%20MS%20Wills.pdf
Multiple sclerosis and occult gluten sensitivity. Connie D.S.N.A. Pengiran Tengah, MRCP; Robert J. Lock, MPhil; D. Joseph Unsworth, PhD; and Adrian J. Wills, MD

Abstract—Two atypical patients with a multiple sclerosis (MS)–like illness and evidence of occult celiac disease (CD) were managed by the authors. This prompted screening of a further 49 unselected MS cases for serologic evidence of CD. IgA anti-endomysial antibody was found in one case (2%). IgG anti-gliadin antibody was found in 12% of patients and 13% of blood donors. Anti-gliadin antibody (especially IgG isotype) can be a nonspecific finding. NEUROLOGY 2004;62:2326–2327

http://www.celiac.com/articles/124/1/Multiple-Sclerosis-and-Celiac-Disease/Page1.html
Multiple Sclerosis and Celiac Disease

Wikipedia

http://en.wikipedia.org/wiki/Celiac_sprue
Four serological blood tests exist for coeliac disease. The most widely used ones detect an antibody of the IgA type against particular antigens in the small bowel. Older tests detected antibodies against reticulin (ARA) or gliadin (AGA), but recent evidence supports the use of the more modern tests, namely those detecting IgA antibodies against endomysium (EMA) or tissue transglutaminase (TTG). Generally, serology may be unreliable in young children, with anti-gliadin performing somewhat better than other tests in children under five.[25] Serology tests are based on indirect immunofluorescence (reticulin, gliadin and endomysium) or ELISA (gliadin or tissue transglutaminase).[26]

Guidelines recommend that a total serum IgA level is checked in parallel, as coeliac patients with IgA deficiency may be unable to produce the antibodies on which these tests depend ("false negative"). In those patients, IgG antibodies against transglutaminase (IgG-TTG) may be diagnostic.[27]

Genetic Basis for Celiac  HLA DQ2

http://en.wikipedia.org/wiki/Celiac_Disease#_note-pmid17785484
Other tests that may assist in the diagnosis are blood tests for a full blood count, electrolytes, calcium, renal function, liver enzymes, vitamin B12 and folic acid levels. Coagulation testing (prothrombin time and partial thromboplastin time) may be useful to identify deficiency of vitamin K, which predisposes patients to hemorrhage. These tests should be repeated on follow-up, as well as anti-tTG titres.[3]
Some professional guidelines[3] recommend screening of all patients for osteoporosis by DXA/DEXA scanning.
Almost all coeliac patients have an abnormal HLA DQ2 allele.[1]

Over 95% of coeliac patients have an isoform of DQ2 (encoded by DQA1*05 and DQB1*02 genes) and DQ8 (encoded by the haplotype DQA1*03QB1*0302), which is inherited in families. The reason these genes produce an increase in risk of coeliac disease is that the receptors formed by these genes bind to gliadin peptides more tightly than other forms of the antigen-presenting receptor. Therefore, these forms of the receptor are more likely to activate T lymphocytes and initiate the autoimmune process.[1]

The frequency of these genes varies geographically. DQ2.5 has high frequency in peoples of North and Western Europe (Basque Country, Ireland,[34] with highest frequencies), portions of Africa, and is associated disease in India,[35] but is not found along portions of the West Pacific rim. DQ8, spread more globally than DQ2.5, is more prevalent from South and Central America (up to 90% phenotype frequency).[36]

Screening and case finding people with undetected coeliac disease had (less overweight, lower cholesterol levels). In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends screening for coeliac disease in patients with newly diagnosed

1) chronic fatigue syndrome
2) irritable bowel syndrome
3) autoimmune thyroid disease. Hashimotos
4) type 1 diabetes,
5) unexplained iron-deficiency anemia
6) Down's syndrome, Turner's syndrome,
7) lupus

http://www.ncbi.nlm.nih.gov/pubmed/8851726
Tissue Antigens. 1996 Feb;47(2):127-33. HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland.Michalski JP, McCombs CC, Arai T, Elston RC, Cao T, McCarthy CF, Stevens FM.

Department of Internal Medicine, University of South Alabama, Mobile, USA.

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world.

http://www.nicholsinstitute.com/Transplant/HLA%20TM%20D.pdf
Nichols DNA Test for Celiac 17135X HLA Typing for Celiac Disease 86817
Assess risk of celiac disease in symptomatic(HLA-DQ2 and -DQ8) patients and in family members of patients with celiac disease

http://en.wikipedia.org/wiki/CELIAC1
HLA-DQB1

http://en.wikipedia.org/wiki/Gluten-free_diet
Vitamin K-deficiency, A small proportion (10%) have abnormal coagulation due to deficiency of vitamin K, and are slightly at risk for abnormal bleeding.

http://www.aetna.com/cpb/medical/data/500_599/0561.html
Aetna considers testing of anti-gliadin, anti-reticulin, IgA anti-human tissue transglutimase (TTG), and IgA anti-endomysial antibodies (EMA) medically necessary for any of the following indications:

As a preliminary diagnostic test for persons with symptoms suggestive of celiac disease; or To monitor response to a gluten-free diet; or For screening first-degree relatives of individuals with celiac disease; or To screen persons with type 1 diabetes for celiac disease.

Aetna considers measurement of total serum IgA, and genetic testing for HLA-DQ2 and HLA-DQ8 haplotypes medically necessary for members with symptoms suggestive of celiac disease and indeterminate serology results.

Aetna considers IgG-TTG and IgG-EMA medically necessary for persons with symptoms suggestive of celiac disease and a serum IgA deficiency.\

On Line Genetic Testing for Celiac Disease

http://www.timesonline.co.uk/tol/news/uk/science/article3463550.ece 
Online genetic testing for 20 diseases From The TimesMarch 1, 2008. Handle with care: genetic tests are risky, and I’ve got the proof. A new online service uses your DNA to assess your risk of developing disease. Our correspondent paid £500 to learn his fate Mark Henderson. See www.deCODEme.com and www.23andMe.com

http://www.decodeme.com/ 
Decodeme. For only $985, we scan over one million variants in your genome Calculate genetic risk for 20 diseases based on the current literature Find out where your ancestors came from and compare your genome with others. Our current list of diseases includes: Age-related macular degeneration, Alzheimer's disease,
Asthma, Atrial fibrillation, Breast Cancer, Celiac Disease, Colorectal Cancer, Crohn's disease, Exfoliation Glaucoma XFG, Hemochromatosis, Lactose Intolerance, Multiple sclerosis, Myocardial Infarction, Obesity, Prostate cancer,
Psoriasis, Restless legs, Rheumatoid arthritis, Type 1 Diabetes, Type 2 Diabetes .

https://www.23andme.com/
23 and me online genetic testing.

Adrenal Insufficiency, Adrenal Fatigue

http://www.ncbi.nlm.nih.gov/pubmed/17595243
J Clin Endocrinol Metab. 2007 Sep;92(9):3595-8. Epub 2007 Jun 26. Risk of primary adrenal insufficiency in patients with celiac disease. .Elfström P, Montgomery SM, Kämpe O, Ekbom A, Ludvigsson JF.

CONCLUSIONS: This study found a highly increased risk of AD (adrenal insufficnecy) in individuals with CD (celiac disease).  We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.

Aliment Pharmacol Ther. 2007 Jun 1;25(11):1317-27. Links
http://www.ncbi.nlm.nih.gov/pubmed/17509100

Neurological Disease and Celiac Disease, polyneuropathy

A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases.Ludvigsson JF, Olsson T, Ekbom A, Montgomery SM.

BACKGROUND: It has been suggested that coeliac disease (CD) is associated with several neurological diseases. However, the evidence of such an association is inconclusive as earlier research has often been based on small numbers with retrospective data collection. AIM: To use Cox regression to examine the risk of neurological disease in individuals with CD. METHODS: Through Swedish national registers we identified some 14 000 individuals with a diagnosis of CD (1964-2003) and 70 000 reference individuals matched for age, sex, calendar year and county.

RESULTS: Coeliac disease was associated with later polyneuropathy [hazard ratio (HR) = 3.4; 95% CI = 2.3-5.1]. We found no statistically significant association between CD and subsequent multiple sclerosis (HR = 0.9; 95% CI = 0.3-2.3), Parkinson's disease (HR = 1.2; 95% CI = 0.8-1.9), Alzheimer's disease (HR = 1.5; 95% CI = 0.9-2.6), hereditary ataxia (HR = 1.3; 95% CI = 0.5-3.6), the symptom ataxia (HR = 1.9; 95% CI = 0.6-6.2), Huntington's disease (HR = 1.7; 95% CI = 0.3-8.6), myasthenia gravis (HR = 0.8; 95% CI = 0.2-3.8) or spinal muscular atrophy (HR = 0.5; 95% CI = 0.1-3.8). Prior polyneuropathy was associated with subsequent CD (odds ratio = 5.4; 95% CI = 3.6-8.2).

CONCLUSIONS: The association between CD and polyneuropathy indicates shared risks. We suggest that individuals with polyneuropathy routinely undergo screening for CD. There is no notable association between CD and other neurological outcomes investigated in this study.

http://www.ncbi.nlm.nih.gov/pubmed/17688758
A case-control study of presentations in general practice before diagnosis of coeliac disease. Br J Gen Pract. 2007 Aug;57(541):636-42.  BACKGROUND: Delay in the diagnosis of coeliac disease prolongs morbidity and may increase mortality. Little is known about presentations in general practice that may predict a subsequent diagnosis of coeliac disease. AIM: To examine presentations in general practice during the 5 years prior to diagnosis of coeliac disease. DESIGN OF STUDY: A case-control study with each biopsy-proven coeliac disease case matched by age, sex, and general practice to an average of two controls. SETTING: Thirty-seven general practices in south-east Wales.

METHOD: Cases were identified via a secondary care clinic and controls recruited from the general practices of cases. General practice clinical records of both cases and controls were analysed to determine frequency of consultations, presenting symptoms, diagnoses, referrals, and investigations during the 5 years prior to diagnosis. RESULTS: Cases (n = 68) had an increased number of consultations compared with controls (n = 160) during the 5 years prior to diagnosis (mean difference five consultations, P = 0.001). Three clinical features were independently associated with subsequent diagnosis of coeliac disease: depression and/or anxiety (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.1 to 5.7, P = 0.031); diarrhoea (OR = 4.5, 95% CI = 2.0 to 10.0, P <0.001); and anaemia (OR = 26.3, 95% CI = 5.7 to 120.6, P <0.001). Both diarrhoea and anaemia remained associated even when data for the year prior to diagnosis was excluded from the analysis.

CONCLUSION: GPs should consider testing for coeliac disease when patients present often, especially with diarrhoea and/or who are discovered to be anaemic. Further research is required to clarify the role of depression and/or anxiety in the diagnosis of coeliac disease.

Celiac and Hashimotos's

http://www.clinmedres.org/cgi/content/full/5/3/184
Clin Med Res. 2007 Oct;5(3):184-92.  Celiac disease and autoimmune thyroid disease.\Ch'ng CL, Jones MK, Kingham JG. Department of Gastroenterology, Singleton Hospital, Swansea, United Kingdom.

http://www.ncbi.nlm.nih.gov/pubmed/17461476 
World J Gastroenterol. 2007 Mar 21;13(11):1715-22.
Coeliac disease in Dutch patients with Hashimoto's thyroiditis and vice versa. Hadithi M, de Boer H, Meijer JW, Willekens F, Kerckhaert JA, Heijmans R, Peña AS, Stehouwer CD, Mulder CJ.

AIM: To define the association between Hashimoto's thyroiditis and coeliac disease in Dutch patients. METHODS: A total of 104 consecutive patients with Hashimoto's thyroiditis underwent coeliac serological tests (antigliadins, transglutaminase and endomysium antibodies) and HLA-DQ typing. Small intestinal biopsy was performed when any of coeliac serological tests was positive. On the other hand, 184 patients with coeliac disease were subjected to thyroid biochemical (thyroid stimulating hormone and free thyroxine) and thyroid serological tests (thyroglobulin and thyroid peroxidase antibodies).

RESULTS: Of 104 patients with Hashimoto's thyroiditis, sixteen (15%) were positive for coeliac serology and five patients with documented villous atrophy were diagnosed with coeliac disease (4.8%; 95% CI 0.7-8.9). HLA-DQ2 (and/or -DQ8) was present in all the five and 53 patients with Hashimoto's thyroiditis (50%; 95% CI 43-62). Of 184 patients with coeliac disease, 39 (21%) were positive for thyroid serology. Based on thyroid biochemistry, the 39 patients were subclassified into euthyroidism in ten (5%; 95% CI 2-9), subclinical hypothyroidism in seven (3.8%; 95% CI 1.8-7.6), and overt hypothyroidism (Hashimoto's thyroiditis) in 22 (12%; 95% CI 8-16). Moreover, four patients with coeliac disease had Graves' disease (2%; 95% CI 0.8-5) and one patient had post-partum thyroiditis.

CONCLUSION: The data from a Dutch population confirm the association between Hashimoto's thyroiditis and coeliac disease. Screening patients with Hashimoto's thyroiditis for coeliac disease and vice versa is recommended.

http://edrv.endojournals.org/cgi/content/full/23/4/464
Endocr Rev. 2002 Aug;23(4):464-83. Endocrinological disorders and celiac disease.Collin P, Kaukinen K, Välimäki M, Salmi J. Department of Medicine, Tampere University Hospital and University of Tampere, 33014 Tampere, Finland.


http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2001.03616.x
The American Journal of Gastroenterology Vol. 96 Issue 3 Page 745 March 2001
Vitamin B12 deficiency in untreated celiac disease Anna Dahele M.R.C.P. (UK), Subrata Ghosh M.D., (Edin)

ICD-9-CM Diagnosis 579.0  Celiac disease

Jeffrey Dach MD www.drdach.com 
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