by Jeffrey Dach MD
Jim suffered from frequent migraines which were severe and incapacitating. After seeing a number of neurologists and trying multiple medications with no improvement, Jim finally came to see me. His last neurologist found he had a low vitamin D level, and started Jim on 10,000 units per day of vitamin D3. Jim reported that his psoriatic skin lesions were markedly better. However, his migraines were unchanged.
Above left image: courtesy of wikimedia commons, Girl With Wheat Painting by Antonio Carvalho de Silva Porto, http://commons.wikimedia.org/wiki/Category:Antonio_Carvalho_de_Silva_Porto
A connection between gluten sensitivity and psoriasis is well known. (18-20) I explained to Jim that food allergies can cause migraines (7), and gluten sensitivity can cause migraine headaches as well (8,9). In fact, gluten sensitivity is associated with all sorts of neurological disorders: cerebellar ataxia, epilepsy, myoclonic ataxia, chronic neuropathies, and dementia, mainly in middle-aged adults.(10-13) I suggested to Jim that it was very probable that a gluten free diet would be helpful in reducing his migraines.(8-9)
Jim’s lifestyle made it difficult for him to go Gluten free, so I suggested he try the EnteroLabs gluten test. Sure enough, the test panel came back positive. Jim went on a gluten free diet, and 4 weeks later called me to report his migraines were much better. This article will discuss sensitivity to wheat gluten, a condition which is epidemic, yet mainly ignored or unknown by the medical system.(20)
left image: Bread, courtesy of wikimedia commons http://commons.wikimedia.org/wiki/File:Strucla_sweet_bread.jpg
Gluten is a protein is wheat products, such as bread, pasta, wheat cereals etc. About 1% or more of the population reacts to wheat gluten with an immune response and an inflammatory disorder of the small intestine which may cause malabsorption of key minerals, amino acids and vitamins. This has an inherited autoimmune component and genetic testing is available.(17) Other diagnostic testing involves looking for the antibodies called TTG (transglutaminase) in stool or blood samples.
The immune response involves production of various antibodies and immune cells which damages the small intestine, reducing its absorptive ability. This is called malabsorption, and results in the inability to absorb key vitamins and minerals such as Iron, Calcium, folate and B12. These abnormalities will show up on the blood count as iron deficiency anemia, and B12/folate deficiency anemia.(22) gluten sensitivity, celiac disease may cause malabsorption of calcium, and the DEXA bone density scan may show osteoporosis (21).
The auto-immune response can circulate freely through the body, crossreacting with other organ systems, unpredictably.
Another common place for the immune response to attack is the skin, with a characteristic skin lesion called Dermatiformis Herpetiformis (it resembles Herpes) with intense burning, itching and blistering skin rash which is usually symmetrically distributed on the elbows, knees and the buttocks. The rash usually starts as small blisters that errupt into small erosions. Dermatologists will make the diagnosis of gluten sensitivity by doing a skin biopsy showing characteristic findings. Immunofluorescence of normal skin next to the vesicle typically shows granular IgA deposits in the upper dermis. (27-29) If the scalp is involved, this is called Alopecia Areata with patchy hair loss caused by auto-antibodies reacting with the hair follicles.(25-26)
In some younger people, Gluten sensitivity may cause acne, and trying a gluten free diet is yield remarkable improvement in the acne.
If the immune response attacks the vascular system, there may be increased venous thrombo-embolism, stroke (2)(3), and coronary artery disease, etc. Thus, gluten sensitivity is one of the major causes of migraine headaches since it may cause inflammation of cerebral arteries, or the brain itself. (9)
If the immune response attacks the brain or spinal cord, this may cause a neurological disorder (4, 10-16) such as ataxia (5), uncoordination, peripheral neuropathy (tingling with pins and needles)(6).
The patient with gluten sensitivity may end up at the endocrinologist’s office with issues such as: Type 1 diabetes mellitus, autoimmune thyroid disease, Addison disease, osteomalacia, secondary hyperparathyroidism, vitamin D or iron deficiency, fertility problems, hypogonadism in men, and autoimmune hypopituitarism.(23) Autioimmune thyroid disease is especially common among people with gluten sensitivity, with elevated anti-thyroid antibodies (Hashimotos) which decrease after initiating a gluten free diet.(24) One can make a case for gluten sensitivity testing for all patients with autoimmune thyroid disease (Hashimotos).
The gluten sensitive patient may have heart involvement with cardiomyopathy, a serious and potentially lethal form of heart failure. In addition, the gluten sensitive individual may have heart rhythm abnormalities such as atrial fibrillation, reversible with a gluten free diet, if diagnosed early. Testing for gluten sensitivity should be done for such patients. (30-31)
A unusual lung disease of unknown etiology called Sarcoidosis is linked to gluten sensitivity and celiac disease.(34) Sarcoidosis is thought to be an auto-immune disease because the treatment is immune suppression with prednisone. Studies have shown “Leaky Gut” and altered GI immune reactivity in Sarcoidosis patients.(36-37). These patients may benefit from a gluten free diet.
Sarcoidosis patients are unusually sensitive to Vitamin D, and symptoms may worsen when exposed to this vitamin. It would therefore be beneficial for sarcoidosis patients to avoid Vitamin D supplements, and also avoid Vitamin D from sun exposure. Certain foods contain vitamin D activity, such as the NightShade Vegetables (eggplant, tomatoes, peppers, and potatoes). Nightshades may contain glyco-alkaloids which have Vitamin D-like activity, so avoiding Nightshafes would be porudent for the Sarcoidosis patient..
Complete failure of the adrenal glands to manufacture cortisol is called Addisons Disease and is associated with gluten sensitivity.(35) These patients may benefit from a gluten free diet.
Left Image :Courtesy of wikimedia commons, http://commons.wikimedia.org/wiki/File:Gluten-free-enterprises-logo.jpg
Patients may go for decades with health problems, running through a succession of doctors, yet remain undiagnosed by the mainstream medical system. Treatment is usually curative with a Gluten Free Diet (GFD) which means avoiding all wheat products such as breads, pasta, wheat cereals, bakery goods etc.
Articles with related interest:
Links and References
Medical Progress, Celiac Disease, Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D. N Engl J Med 357;17 october 25, 2007
Celiac Disease and Stroke
Pediatr Neurol. 2004 Aug;31(2):139-42.
Celiac disease and childhood stroke. Goodwin FC, Beattie RM, Millar J, Kirkham FJ.
Celiac disease is associated with a diversity of central nervous system manifestations although an association with stroke has not been documented. This case report describes a child who presented with a recurrent transient hemiplegia. Magnetic resonance imaging of the brain confirmed infarction; transcranial Doppler studies and magnetic resonance angiography were abnormal. Although there were virtually no gastrointestinal symptoms and the child was thriving, celiac disease serology was strongly positive and a duodenal biopsy confirmed the disease. Tissue transglutaminase is the major autoantigen in celiac disease and is thought to maintain vascular endothelial integrity. Antiendomysial immunoglobulin A antibodies, demonstrated to be the same autoantibody as antitransglutaminase, react with cerebral vasculature, suggesting an autoimmune mechanism for celiac disease associated vasculopathy. Because celiac disease is a potentially treatable cause of cerebral vasculopathy, serology-specifically antitissue transglutaminase antibodies-should be included in the evaluation for cryptogenic stroke in childhood, even in the absence of typical gut symptoms.
Rev Neurol (Paris). 2009 Nov;165(11):962-6. Epub 2009 Jan 13.
[Celiac disease and ischemic stroke].[Article in French] El Moutawakil B, Chourkani N, Sibai M, Moutaouakil F, Rafai M, Bourezgui M, Slassi I.
Neurological manifestations of celiac disease are various. An association with ischemic stroke is not common and has not been well documented. We report two cases.
OBSERVATIONS: The first patient had experienced several transient ischemic strokes in the past 2 years and then had an acute ischemic stroke involving the territory of the right posterior cerebral artery. Investigations revealed celiac disease with no other recognizable etiology. The clinical course was marked by persistent visual aftereffects, but no new vascular event. The second patient had been followed since 1998 for celiac disease confirmed by pathology and serology tests. She was on a gluten-free diet. The patient had an ischemic stroke involving the territory of the left middle cerebral artery. Apart from a positive serology for celiac disease and iron deficiency anemia, the etiological work-up was negative.
DISCUSSION: The mechanisms of vascular involvement in celiac disease are controversial. The most widely incriminated factor is autoimmune central nervous system vasculitis, in which tissue transglutaminase, the main auto-antigen contributing to maintaining the integrity of endothelium tissue, plays a major role. Other mechanisms are still debated, mainly vitamin deficiency.
CONCLUSION: Being a potentially treatable cause of ischemic stroke, celiac disease must be considered as a potential etiology of stroke of unknown cause, particularly in young patients, and even without gastrointestinal manifestations.
Gluten and Neurological Disorder
Mov Disord. 2009 Dec 15;24(16):2358-62. Neurological symptoms in patients with biopsy proven celiac disease. Bürk K, Farecki ML, Lamprecht G, Roth G, Decker P, Weller M, Rammensee HG, Oertel W.
(5) www.ncbi.nlm.nih.gov http: href?>www.ncbi.nlm.nih.gov/pubmed/12566288
Brain. 2003 Mar;126(Pt 3):685-91. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Hadjivassiliou M, Grünewald R, Sharrack B, Sanders D, Lobo A, Williamson C, Woodroofe N, Wood N, Davies-Jones A.
Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia.
Lancet Neurol 2010; 9: 318–30 Gluten sensitivity: from gut to brain.
Marios Hadjivassiliou, David S Sanders, Richard A Grünewald, Nicola Woodroofe, Sabrina Boscolo, Daniel Aeschlimann
Migraines and Food Allergies – wheat
Lancet. 1979 May 5;1(8123):966-9.
Food allergies and migraine.Grant EC. Abstract 60 migraine patients completed elimination diets after a 5-day period of withdrawal from their normal diet. 52 (87%) of these patients had been using oral contraceptive steroids, tobacco, and/or ergotamine for an average of 3 years, 22 years, and 7.4 years respectively. The commonest foods causing reactions were wheat (78%), orange (65%), eggs (45%), tea and coffee (40% each), chocolate and milk (37%) each), beef (35%), and corn, cane sugar, and yeast (33% each). When an average of ten common foods were avoided there was a dramatic fall in the number of headaches per month, 85% of patients becoming headache-free. The 25% of patients with hypertension became normotensive. Chemicals in the home environment can make this testing difficult for outpatients. Both immunological and non-immunological mechanisms may play a part in the pathogenesis of migraine caused by food intolerance.
Migraines and Celiac
Am J Gastroenterol. 2003 Jul;98(7):1674; March edition of American Journal of Gastroenterology. Association Between Migraine and Celiac Disease: Results From a Preliminary Case-Control and Therapeutic Study. Maurizio Gabrielli MD et al.
American Academy of Neurology (2001, February 14); Gluten In The Diet May Be The Cause Of Recurring Headaches; Science Daily.
Lancet Neurol 2010; 9: 318–30
Gluten sensitivity: from gut to brain. Marios Hadjivassiliou, David S Sanders, Richard A Grünewald, Nicola Woodroofe, Sabrina Boscolo, Daniel Aeschlimann
The gluten syndrome: A neurological disease… Rodney Philip Kinvig Ford *
The Children’s Gastroenterology and Allergy Clinic, P.O. Box 25-265, Christchurch 8144, New Zealand
M Hadjivassiliou – acnr.co.uk ACNR 2003 Gluten and neurologic disorders
Range of Neurologic Disorders in Patients With Celiac Disease
Nathanel Zelnik, MD, Avi Pacht, MD, Raid Obeid, MD, Aaron Lerner, MD
From the Department of Pediatrics, Carmel Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
2010 Lancet PDF latest article
Lancet Neurol 2010; 9: 318–30 Gluten sensitivity: from gut to brain
Marios Hadjivassiliou, David S Sanders, Richard A Grünewald, Nicola Woodroofe, Sabrina Boscolo, Daniel Aeschlimann
Narrative Review: Celiac Disease: Understanding a Complex Autoimmune Disorder
Armin Alaedini, PhD, and Peter H.R. Green, MD Ann Intern Med. 2005;142:289-298.
Living Gluten-Free: An Analysis of Illness and Coping Narratives. Authors: Dougher, Carly E. Citation URL: http://hdl.handle.net/1957/17611
Abstract: Gluten intolerance is a condition that affects a significant portion of the world’s population. While awareness about the condition has recently increased, the condition remains poorly understood and therefore commonly mis- and underdiagnosed. In this paper, I examine the challenges in obtaining a gluten intolerant diagnosis and attempt to capture the experience of living gluten-free in a wheat-dependent society. Through interviews with gluten intolerant individuals in the Pacific Northwest, I expose a perceived lack of awareness and understanding about the condition in the western biomedical community that presented challenges for the participants pre-diagnosis, as well as a perceived lack of awareness and understanding about the condition in the general community that presented challenges for the participants post-diagnosis. Based on common themes extrapolated from these interviews, I argue that the western biomedical community as a whole lacks a complete understanding of the entire spectrum of gluten intolerance and that the information about gluten intolerance in published scientific literature does not match the lived experience.
Trends Mol Med. 2010 Nov;16(11):537-50. Epub 2010 Oct 12.
A genetic perspective on coeliac disease. Trynka G, Wijmenga C, van Heel DA.
Coeliac disease is an inflammatory disorder of the small intestine with an autoimmune component and strong heritability. Genetic studies have confirmed strong association to HLA and identified 39 nonHLA risk genes, mostly immune-related. Over 50% of the disease-associated single nucleotide polymorphisms are correlated with gene expression. Most of the coeliac disease-associated regions are shared with other immune-related diseases, as well as with metabolic, haematological or neurological traits, or cancer. We review recent progress in the genetics of coeliac disease and describe the pathways these genes are in, the functional consequences of the associated markers on gene expression and the genes shared between coeliac disease and other traits.
Celiac and Psoriasis Association
Celiac disease and skin: Psoriasis association. L Abenavoli, L Leggio, G Gasbarrini, G Addolorato . World J Gastroenterol 2007 April 14; 13(14): 2138-2139
Rapid Regression of Psoriasis in a Coeliac Patient after Gluten-Free Diet
A Case Report and Review of the Literature
Giovanni Addoloratoa, Antonio Parentea, Giosue de Lorenzia, Maria Eugenia D’angelo Di Paolaa, Ludovico Abenavolia, Lorenzo Leggioa, Esmeralda Capristoa, Clara De Simoneb, Maurizio Rotolib, Gian Ludovico Rapaccinia, Giovanni Gasbarrinia
(20) Celiac Disease (Revised and Updated Edition) A Hidden Epidemic By Peter H.R. Green, M.D., Rory Jones William Morrow and Company, 2010
Celiac and Osteoporosis
Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis. Stenson WF, Newberry R, Lorenz R, Baldus C, Civitelli R.
CONCLUSIONS: The prevalence of celiac disease among osteoporotic individuals (3.4%) is much higher than that among nonosteoporotic individuals (0.2%). The prevalence of celiac disease in osteoporosis is high enough to justify a recommendation for serologic screening of all patients with osteoporosis for celiac disease.
Hematologic Manifestations of Celiac
Hematologic manifestations of celiac disease . Thorvardur R. Halfdanarson1,, Mark R. Litzow1, and Joseph A. Murray2, Division of Hematology and 2 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
Patients with celiac disease may present to hematologists for evaluation of various hematologic problems prior to receiving a diagnosis of celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency.
Celiac Disease and Endocrine Disorders
Endocr Pract. 2008 Apr;14(3):381-8. Celiac disease and the endocrinologist: a diagnostic opportunity. Fisher AH, Lomasky SJ, Fisher MJ, Oppenheim YL.
OBJECTIVE: To review the association of celiac disease and various endocrine disorders and present the related clinical experience of a 3-physician adult endocrinology practice.
METHODS: We provide an overview of the pertinent literature, discuss the clinical manifestations, genetics, and pathogenesis of celiac disease, and describe our clinical experience during a 5-year period.
RESULTS: Celiac disease has been associated with numerous disorders, including several conditions treated by endocrinologists-type 1 diabetes mellitus, autoimmune thyroid disease, Addison disease, osteomalacia, secondary hyperparathyroidism, vitamin D or iron deficiency, fertility problems, hypogonadism in men, and autoimmune hypopituitarism. After our clinical awareness was raised about these potential comorbidities, 18 patients were newly diagnosed with celiac disease in our clinical practice during a 5-year interval. All patients had been referred for endocrine evaluation or were undergoing follow-up for ongoing management of endocrine disorders. When a “celiac-associated” endocrine disorder coexists with other factors associated with celiac disease, we recommend performance of IgA class antibody testing, and either antiendomysial or anti-tissue transglutaminase antibodies provide high specificity and sensitivity for the diagnosis of celiac disease.
CONCLUSION: Endocrinologists have an opportunity to diagnose celiac disease, a relatively common disorder with profound clinical implications that can often be associated with various endocrinopathies.
Thyroid Disorders in Celiac patients
Am J Gastroenterol. 2001 Mar;96(3):751-7. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Sategna-Guidetti C et al.
METHODS: A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies.
RESULTS: Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later.
CONCLUSIONS: The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.
(25) http://www.ncbi.nlm.nih.gov/pubmed/8176253 J Invest Dermatol. 1994 May;102(5):721-4. Antibodies to hair follicles in alopecia areata. Tobin DJ, Orentreich N, Fenton DA, Bystryn JC.
(26) http://www.ncbi.nlm.nih.gov/pubmed/16338213 Autoimmun Rev. 2006 Jan;5(1):64-9. Epub 2005 Aug 8. Alopecia areata: a tissue specific autoimmune disease of the hair follicle.Gilhar A, Kalish RS.
Dermatitis HerPetiformis: Skin Manifestation of Celiac Disease. A skin biopsy is the first step in diagnosing DH. Direct immunofluorescence of clinically normal skin adjacent to a lesion shows granular IgA deposits in the upper dermis.
(28) http://www.ncbi.nlm.nih.gov/pubmed/19344979 Rose C, Armbruster FP, Ruppert J, Igl BW, Zillikens D and Shimanovich I Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet. J Am Acad Dermatol 2009; 61:39-43
Zone JJ Skin manifestations of celiac disease.
(29) http://www.ncbi.nlm.nih.gov/pubmed/16521210 Abenavoli L, Proietti I, Leggio L, et al. Cutaneous manifestations in celiac disease. World Journal of Gastroenterology. 2006;12(6):843–852.
Celiac Disease and Dilated Cardiomyopathy
30 (27) http://www.ncbi.nlm.nih.gov/pubmed/10421311
Curione M, Barbato M, De Biase L, Viola F, Lo Russo L, Cardi E. Prevalence of Coeliac Disease in Idiopathic Dilated Cardiomyopathy. The Lancet 1999; 354: 222-223.
31 (28) http://www.mayoclinicproceedings.com/content/80/5/674.full.pdf
Cardiomyopathy Associated With Celiac Disease . Mayo Clin Proc. 2005;80(5):674-676
CASE REPORT NISHEETH K. GOEL, MD; ROBERT D. MCBANE, MD; AND PATRICK S. KAMATH, MD . Celiac disease in adults is often asymptomatic or presents with extremely few symptoms. A high degree of clinical suspicion is required to make a prompt and correct diagnosis
Celiac Disease and Coronary artery Disease
Risk of Coronary Artery Disease in Celiac Disease Patients
Ludvigsson JF et al 2007 was a Swedish national hospital based study looking at 13,358 CD patients, which found increased MI (HR 1.27, 95% CI 1.09 to 1.48) and angina pectoris (1.46, 1.25 to 1.70).
Heart. 2007 September; 93(9): 1111–1115.
Vascular disease in a population‐based cohort of individuals hospitalised with coeliac disease J F Ludvigsson, U de Faire, A Ekbom, and S M Montgomery
CD was associated with myocardial infarction (HR 1.27; 95% CI 1.09 to 1.48), angina pectoris (1.46; 1.25 to 1.70), heart failure (1.41; 1.22 to 1.62), brain haemorrhage (1.40; 1.05 to 1.88) and ischaemic stroke (1.35; 1.14 to 1.60). These risk estimates were similar when analyses were restricted to adults in whom vascular disease had been listed as the main diagnosis. In post‐hoc analyses, where reference individuals were restricted to inpatients, no association was found between CD and later vascular disease, except for a lower risk of heart failure (0.79; 0.68 to 0.92).
Celiac and Sarcoidosis
Sarcoidosis Vasc Diffuse Lung Dis. 2007 Sep;24(2):121-6.
Coeliac disease and risk of sarcoidosis.
Ludvigsson JF, Wahlstrom J, Grunewald J, Ekbom A, Montgomery SM.
BACKGROUND AND AIM: Several case reports indicate a link between coeliac disease (CD) and sarcoidosis. Our main objective was to investigate the risk of subsequent sarcoidosis in individuals with CD in a general population cohort study. A second aim was to estimate the risk of CD in individuals with prior sarcoidosis.
METHODS: We used Cox proportional hazards method to calculate the risk of subsequent sarcoidosis in 14,349 individuals who had received a diagnosis of CD (1964-2003) and 69,998 age- and sex-matched individuals without a diagnosis of CD. Subjects were identified through the Swedish national Inpatient Register. Conditional logistic regression was used to study the risk of CD associated with prior sarcoidosis.
RESULTS: CD was associated with an increased risk of sarcoidosis (Hazard ratio (HR) = 4.03; 95% CI = 2.32-7.00; p < 0.001), and was not notably affected by adjustment for socioeconomic index. In individuals with CD listed as the main diagnosis, the HR was 3.66 (95% CI HR = 1.80-7.45; p < 0.001). Prior sarcoidosis was associated with an increased risk of CD (Odds ratio = 3.58; 95% CI = 1.98-6.45; p < 0.001).
CONCLUSION: Immune characteristics of CD may be linked to an increased risk of sarcoidosis.
(35) Celiac and Primary Adrenal insufficiency
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.
Department of Pediatrics, Orebro University Hospital, SE-701 85 Orebro, Sweden.
OBJECTIVES: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD). We have here investigated the risk of AD in individuals with CD from a general population cohort.
METHODS: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964-2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.
RESULTS: There was a statistically significantly positive association between CD and subsequent AD [HR = 11.4; 95% confidence interval (CI) = 4.4-29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI = 1.9-11.4). Individuals with prior AD were at increased risk of CD (odds ratio = 8.6; 95% CI = 3.4-21.8).
CONCLUSIONS: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.
J Intern Med. 1999 May;245(5):525-31.
Evidence of gastrointestinal immune reactivity in patients with sarcoidosis.
Papadopoulos KI, Sjöberg K, Lindgren S, Hallengren B.
Department of Endocrinology, University of Lund, Malmö University Hospital, Sweden.
The aim of the present study was to explore the frequency of clinical and serological manifestations of gastrointestinal immune reactivity in a large group of Swedish patients with sarcoidosis.
In patients with documented sarcoidosis, the presence of pernicious anaemia and coeliac disease was examined. Antibodies to H+/K+ ATPase, gliadin (AGA-IgA/IgG) and endomysium (IgA-EMA) were analysed. In H+/K+ ATPase antibody-positive patients, serum gastrin levels were measured and, when elevated, gastrointestinal biopsy was offered (biopsy performed in 6/9 patients): biopsy was also offered to those with positive EMA or AGA of either class (biopsy performed in 8/12 patients). Subjects from national and local studies were used as controls.
The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden.
Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 [34 females and 44 males; median age at the time of the study, 48 (range 22-81) years; median observation time since the diagnosis of sarcoidosis, 120 (range 1-468) months] were examined.
Twenty-nine patients (37.2%) had signs of gastrointestinal immune reactivity. H+/K+ ATPase antibodies were detected in 19 patients (24.4 vs. 4% in controls, P = 0.00015). Serum gastrin levels (median 45, range 22-720 pmol L(-1)) in those patients correlated with antibody titre (r2 = 0.882). Gliadin antibodies were detected in 12 patients (15.4 vs. 8.1% in controls, P = 0.042), of whom 11 (14.1 vs. 4.5% in controls, P = 0.00114) had AGA-IgA alone. One patient had pernicious anaemia and another coeliac disease (EMA-positive).
CONCLUSION:We have demonstrated a high frequency of gastric autoimmunity and gluten-associated immune reactivity in patients with sarcoidosis, occurring in almost 40% of the cases, the former being the most frequent gastrointestinal immune manifestation. Despite a high frequency of humoral autoimmunity, the frequencies of clinical disease, pernicious anaemia and coeliac disease were not increased as compared with the control population.
Am Rev Respir Dis. 1992 Jun;145(6):1440-5.
Increased intestinal permeability in active pulmonary sarcoidosis.
Wallaert B, Colombel JF, Adenis A, Marchandise X, Hallgren R, Janin A, Tonnel AB.
SourceService de Pneumologie et Immunoallergologie, Hôpital A. Calmette, Lille, France.
Abstract Altered permeability of the gut is a well-described feature in Crohn’s disease. Because of pathologic similarities between Crohn’s disease and sarcoidosis, we initiated this study to evaluate the permeability of the gut mucosal lining in patients with pulmonary sarcoidosis. A group of 18 patients with biopsy-proven pulmonary sarcoidosis (active n = 8, inactive n = 10) were included in the study. Control groups included 22 patients with Crohn’s disease (active n = 12, inactive n = 10), nine untreated patients with recent pulmonary tuberculosis, six patients with coal worker’s pneumoconiosis (CWP), eight patients with idiopathic pulmonary fibrosis (IPF), and 16 healthy subjects. All were nonsmokers. The 24-h urinary excretion of 100 microCi 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) was used to test the intestinal permeability (IP). As previously demonstrated, patients with active Crohn’s disease demonstrated a dramatic increase in IP (7.7 +/- 1.4%) that was clearly reduced in inactive CD (2.34 +/- 0.54%). Patients with active pulmonary sarcoidosis exhibited a marked increased IP to 51Cr-EDTA (4 +/- 0.54%), which was not found in patients with inactive sarcoidosis (1.6 +/- 0.17%). IP was normal in patients with pulmonary tuberculosis (1.03 +/- 0.25%), CWP (2.1 +/- 0.54%), and IPF (1.9 +/- 0.33%) and did not differ from the control group (1.76 +/- 0.23%). In addition, in 6 patients with active pulmonary sarcoidosis, the concentrations of albumin and hyaluronan were measured in jejunal perfusion fluid and compared with those obtained from 10 patients with active Crohn’s disease and 16 control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Dr. Peter Green Columbia
Medical Progress, Celiac Disease, Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D. n engl j med 357;17 october 25, 2007
The Many Faces of Celiac Disease: Clinical Presentation of Celiac Disease in the Adult Population. PETER H. R., GREEN GASTROENTEROLOGY Vol. 128, No. 4 April Supplement 2005. Celiac Disease Center at Columbia University, Columbia University Medical Center, New York, New York
There is a need for screening studies of patients with conditions associated with celiac disease to determine whether the large numbers of people with undiagnosed celiac disease currently are seeking health care.
Annu. Rev. Immunol. 2000. 18:53–81. MOLECULAR BASIS OF CELIAC DISEASE Ludvig M. Sollid Institute of Immunology, Rikshospitalet,
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.
Barada, Kassem. “Celiac Disease in Middle Eastern and North African Countries: A New
Burden?” World Journal of Gastroenterology 16.12 (2010): 1449-457.
Boelaert, K. “Prevalence and Relative Risk of Other Autoimmune Diseases in Subjects
with Autoimmune Thyroid Disease.” Am J Med. 123.2 (2010): 183.
“‘Celiac Disase’ Most Children Are Now Cured But Cause Is Still Unkown.” The New
York Times [New York] 21 May 1950.
Charmaz, Kathy. Constructing Grounded Theory a Practical Guide through Qualitative
Analysis. Los Angeles, Calif. Sage, 2006.
Clemente, M. G. “Early Effects of Gliadin on Enterocyte Intracellular Signaling Involved
in Intestinal Barrier Function.” Gut 52.21 (2003): 218-23.
Cranney, Anne. “The Canadian Celiac Health Survey – The Ottawa Chapter Pilot.” BMC
Gastroenterology 3.8 (2003).
Dubois, Patrick C.A. “Multiple Common Variants for Celiac Disease Influencing
Immune Gene Expression.” Nature Genetics 42.4 (2010): 295-302.
Farrell, Richard J. “Celiac Sprue.” The New England Journal of Medicine 346.3 (2002):
Fasano, Alessio. “Celiac Disease–How to Handle a Clinical Chameleon.” The New
England Journal of Medicine 248.25 (2003): 2568-570.
Fasano, Alessio. “Current Approaches to Diagnosis and Treatment of Celiac Disease: An
Evolving Spectrum.” Gastroenterology 120 (2001): 636-51.
Fasano, Alessio. “Zonulin, a Newly Discovered Modulator of Intestinal Permeability, and
Its Expression in Coeliac Disease.” Lancet 355.9214 (2000): 1518-519.
Fasano, Alessio. “Prevalence of Celiac Disease in At-risk and Not-at-risk Groups in the
United States: a Large Multicenter Study.” Arch Intern Med. 163.3 (2003): 286-
Ford, Rodney Philip K. “The Gluten Syndrome: A Neurological Disease.” Medical
Hypotheses 73 (2009): 438-40.
“Gluten-Free A Necessity, Not Diet Choice.” The Columbia Chronicle. Columbia
Univeristy, 08 Mar. 2010. Web.
Green, Peter H. R., and Rory Jones. Celiac Disease: a Hidden Epidemic. New York:
Green, Peter HR. “Mortality in Celiac Disease, Intestinal Inflammation, and Gluten
Sensitivity.” JAMA 302.11 (2009): 1225-226.
Hadjivassiliou, M. “Gluten Sensitivity: From Gut to Brain.” Lancet Neurol. 9.3 (2010):
Howdle, P. D. “Gliadin, Glutenin or Both? The Search for the Holy Grail in Coeliac
Disease.” Eur J Gastroenterol Hepatol. 18.7 (2006): 703-06.
Kleinman, 1980. Patients and Healers in the Context of Culture. Berkeley: University of
Lammers, Karen M. “Gliadin Induces an Increase in Intestinal Permeability and Zonulin
Release by Binding to the Chemokine Receptor CXCR3.” Gastroenterology 135.1
Marsh, Michael N. “Is Celiac Disease (Gluten Sensitivity) a Premalignant Disorder?”
Journal of Pediatric Gastroenterology and Nutrition 24 (1997): 25-27.
Marsh, Michael N. “Transglutaminase, Gluten and Celiac Disease: Food for Thought.”
Nature Medicine 3.7 (1997): 725-26.
McManus, Ross. “Celiac Disease–The Villain Unmasked.” The New England Journal of
Medicine 348.25 (2003): 2573-574.
Plenge, Robert M. “Unlocking the Pathogenesis of Celiac Disease.” Nature Genetics
Sollid, Ludvig M. “Molecular Basis of Celiac Disease.” Annu. Rev. Immunol. 18 (2000):
Sudbrack Da Gama E Silva, Tatiana. “Diagnosis of Celiac Disease in Adults.” Rev Assoc
Med Bras 56.1 (2010).
Visser, J. “Tight Junctions, Intestinal Permeability, and Autoimmunity: Celiac Disease
and Type 1 Diabetes Paradigms.” Ann N Y Acad Sci. 1165 (2009): 195-205.
Wangen, Stephen. “The Spectrum of Gluten Intolerance Beyond Celiac Disease.” IBS
Treatment Center. 2008.
Zwolinska-Wcislo, M. “Coeliac Disease and Other Autoimmunological Disorders
Coexistance.” Przegl Lek. 66.7 (2009): 370-72.
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