Extra Intestinal Manifestations of Celiac Disease and Associated Disorders

Abbasi Najmeh¹ and Allameh Seyed Farshad^1,

¹Tehran University of Medical Sciences, Iran

Cite this paper:
Abbasi Najmeh and Allameh Seyed Farshad. Extra Intestinal Manifestations of Celiac Disease and Associated Disorders. International Journal of Celiac Disease. 2017; 5(1):1-9. doi: 10.12691/ijcd-5-1-3

Abstract

Celiac disease (CD) is one of the most common causes of chronic malabsorption in all over the world. CD damage the small intestine epithelial layer. Reduction of absorptive surface area and digestive enzymes, cause impairment of absorption of micronutrients such as fat-soluble vitamins, iron and vitamin B12 and folic acid. Sensitivity to gluten is the main pathophysiologic cause of CD and it is characterized by intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy. CD has diverse clinical features includes anemia, fatigue, weight loss, diarrhea, abdominal pain, bloating, osteoporosis and depression. CD is commonly seen in association with extra intestinal manifestations, such as the typical skin lesions and the neurologic symptoms. Because of the broad spectrum of its presentations, the diagnosis may not be so obvious or easy.Having greater awareness and lower threshold for testing for CD are necessary for diagnosis of this disease. When CD is suspected, serologic testing is required for screening and subsequently duodenal biopsies are necessary to confirm the diagnosis. In this review article we want to review the extra intestinal manifestations of CD and also describe the association between CD and other disorders. It is useful for better diagnosis of CD and improvement of treatment of associated conditions. Future studies should focus on the extra intestinal presentations and associated disorders of gluten sensitivity as they could help better understanding the pathogenesis of gluten sensitivity. In this review article we describe these issues: 1. CD and psychiatric disorders; 2. CD and neurologic disorders; 3. CD and cardiac manifestation; 4. CD and liver disease; 5. CD and Endocrine disease; 6. CD and Dermatologic disease; 7. CD and Rheumatologic disorders; 8. CD and Ophthalmologic disease; 9. CD and Reproductive problems; 10. CD and associations with some other disease.

Keywords:
celiac disease extra intestinal manifestations

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Di Sabatino A, Corazza GR. Coeliac disease. Lancet. 2009; 373: 1480-1493.
[2]	Alberto R T, Ivor D H, Ciarán P K, et al. American college of gastroenterology clinical guideline: diagnosis and management of celiac disease.Am J Gastroenterol. 2013; 108: 656-677.
[3]	Reilly NR, Fasano A, Green PH. Presentation of celiac disease. Gastrointest Endosc Clin N Am.2012; 22: 613-621.
[4]	Rashtak SH, Murray J A. Review Article: Celiac Disease, New Approaches to Therapy. Aliment Pharmacol Ther. 2012; 35: 768-781.
[5]	Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992; 102: 330-354.
[6]	Murray JA, Watson T, Clearman B, et al. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr. 2004; 79: 669-673.
[7]	Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006; 131: 1981-2002.
[8]	Murray JA, Van Dyke C, Plevak MF, et al. Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001. Clin Gastroenterol Hepatol. 2003; 1: 19-27.
[9]	Dube C, Rostom A, Sy R, et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology. 2005; 128: S57-67.
[10]	Catassi C, Ratsch IM, Fabiani E, et al. Coeliac disease in the year 2000: exploring the iceberg. Lancet. 1994; 343: 200-203.
[11]	Zone JJ. Skin manifestations of celiac disease. Gastroenterology. 2005; 128: S87-91.
[12]	Bushara KO. Neurologic presentation of celiac disease. Gastroenterology. 2005; 128: S92-97.
[13]	Green PH. The many faces of celiac disease: clinical presentation of celiac disease in the adult population. Gastroenterology. 2005; 128: S74-78.
[14]	Abdulkarim AS, Murray JA. Review article: The diagnosis of coeliac disease. Aliment Pharmacol Ther. 2003; 17: 987-995.
[15]	Rashtak S, Murray JA. Tailored testing for celiac disease. Ann Intern Med. 2007; 147: 339-341.
[16]	Van der Windt DA, Jellema P, Mulder CJ, et al. Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review. JAMA. 2010; 303: 1738-1746.
[17]	Ludvigsson J F, Bai J C, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology, Gut 2014; 63: 1210-1228.
[18]	Eaton WW, Mortensen PB, Agerbo E, et al. Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers. BMJ 2004; 328: 438-439.
[19]	Kalaydjian AE, Eaton W, Cascella N, et al. The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand 2006; 113: 82-90.
[20]	Chen SI, Chao YL, Chen CY, et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry 2012; 200: 374-380.
[21]	Dickerson F, Stallings C, Origoni A, et al. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode Schizophrenia. Biol Psychiatry 2010; 68: 100-104.
[22]	Samaroo D, Dickerson F, Kasarda D, et al. Novel immune response to gluten in individuals with Schizophrenia. Schizophr Res 2010; 118: 248-255.
[23]	Bender L. Childhood schizophrenia. Psychiat Q 1953; 27: 663-681.
[24]	Dohan FC. Wheat ‘‘consumption’’ and hospital admissions for schizophrenia during World War II. A preliminary report. Am J Clin Nutr 1966; 18: 7-10.
[25]	Porcelli B, Verdino V, Bossini L, et al. Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders Autoimmun Highlights 2014; 5: 55-61.
[26]	Ludvigsson JF, Osby U, Ekbom A, et al. Coeliac disease and risk of schizophrenia and other psychosis: a general population cohort study. Scand J Gastroenterol 2007; 42: 179-185.
[27]	West J, Logan RF, Hubbard RB, et al. Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn’s disease: a general population-based study. Aliment Pharmacol Ther 2006; 23: 71-74.
[28]	Peleg R, Ben-Zion ZI, Peleg A, et al. ‘‘Bred madness’’ revisited: screening for specific celiac antibodies among schizophrenia patients. Eur Psychiatry 2004; 19: 311-314.
[29]	Ludvigsson JF, Reutfors J, Osby U, et al. Coeliac disease and risk of mood disorder-A general population based cohort study. J Affect Disord 2007; 99: 117-126.
[30]	Carta MG, Hardoy MC, Boi MF, et al. Association between panic disorder, major depressive disorder and celiac disease: a possible role of thyroid autoimmunity. J Psychosom Res 2002; 53: 789-793.
[31]	Addolorato G, Mirijello A, DAngelo C, et al. State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting. Int J Clin Pract 2008; 62: 1063-1069.
[32]	Ciacci C, Iavarone A, Mazzacca G, et al. Depressive symptoms in adult celiac disease. Scand J Gastroenterol 1998; 33: 247-250.
[33]	Siniscalchi M, Iovino P, Tortora R, et al. Fatigue in adult coeliac disease. Aliment Pharmacol Ther 2005; 22: 489-494.
[34]	Dickerson F, Stallings C, Origoni A, et al. Markers of gluten sensitivity and celiac disease in bipolar disorder. Bipolar Disord 2011; 13: 52-58.
[35]	Dickerson F, Stallings C, Origoni A, et al. Markers of gluten sensitivity in acute mania: a longitudinal study. Psychiatry Res 2012; 196: 68-71.
[36]	Accomando S, Fragapane ML, Montaperto D, et al. Coeliacdisease and depression: two related entities? Dig Liver Dis 2005; 37: 298-299.
[37]	Roos S, Karner A, Hallert C. Psychological well-being of adult coeliac patients treated for 10 years. Dig Liver Dis 2006; 38: 177-180.
[38]	Cicarelli G, Della RG, Amboni M, et al. Clinical and neurological abnormalities in adult celiac disease. Neurol Sci 2003; 24: 311-317.
[39]	Fera T, Cascio B, Angelini G, et al. Affective disorders and quality of life in adult coeliac disease patients on a gluten-free diet. Eur J Gastroenterol Hepatol 2003; 15: 1287-1292.
[40]	Niederhofer H, Pittschieler K. A preliminary investigation of ADHD symptoms in persons with celiac disease. J Atten Dis. 2006; 10: 200-204.
[41]	Atladottir HO, Pedersen MG, Thorsen P, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2009; 124: 687-694.
[42]	de Magistris L, Familiari V, Pascotto A, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010; 51: 418-424.
[43]	Vaknin A, Eliakim R, Ackerman Z, et al. Neurological abnormalities associated with celiac disease. J Neurol 2004; 251: 1393-1397.
[44]	Visser J, Rozing J, Sapone A, et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009; 1165: 195-205.
[45]	Hadjivassiliou M, Grunewald R, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003; 126: 685-691.
[46]	Chin R L, Sander H W, Brannagan T H, et al. Celiac neuropathy. Neurology. 2003; 60: 1581-1585.
[47]	Ludvigsson J F, Olsson T, EkbomA, et al. A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases. Aliment Pharmacol Ther. 2007; 25: 1317-1327.
[48]	Hadjivassiliou M, Kandler R H, Chattopadhyay A K, et al. Dietary treatment of gluten neuropathy. Muscle and Nerve. 2006; 34: 762-766.
[49]	Luostarinen L, Himanen S L, Luostarinen M, et al. Neuromuscular and sensory disturbances in patients with well treated coeliac disease. J Neurol Neurosurg Psychiatry. 2003; 74: 490-494.
[50]	Shatin R. Gluten and multiple sclerosis. Br Med J. 1965; 29: 1433-1434.
[51]	Rodrigo L, Hernandez L C, Fuentes D, et al. Prevalence of celiac disease in multiple sclerosis. BMC Neurology. 2011; 11: 31.
[52]	Nicoletti A, Patti F, lo Fermo S, et al. Frequency of celiac disease is not increased among multiple sclerosis patients. Multiple Sclerosis. 2008; 14: 698-700.
[53]	Lauret E, Rodrigo L. Celiac Disease and Autoimmune-Associated Conditions. Biomed Res Int 2013: 2013: 127589.
[54]	Hu WT, Murray JA, Greenaway MC, et al. Cognitive impairment and celiac disease. Arch Neurol. 2006; 63: 1440-1446.
[55]	Lurie Y, Landau DA, Pfeffer J, et al. Celiac disease diagnosed in the elderly. J Clin Gastroenterol. 2008; 42: 59-61.
[56]	De SA, Addolorato G, Romito A, et al. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med. 1997; 242: 421-423.
[57]	Nikpour SH. Neurological manifestations, diagnosis, and treatment of celiac disease: A comprehensive review. Ir J neurol 2012; 11: 59-64.
[58]	Garwicz S, Mortensson W. Intracranial calcification mimicking the Sturge-Weber syndrome: a consequence of cerebral folic acid deficiency? Pediatr Radiol.1976; 5: 5-9.
[59]	Green PH, Cellier C. Celiac disease. N Engl J Med. 2007; 357: 1731-1743.
[60]	Hadjivassiliou M, Chattopadhyay AK, Grunewald RA, et al. Myopathy associated with gluten sensitivity. Muscle and Nerve. 2007; 35: 443-450.
[61]	Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and Celiac disease: Results from a preliminary case-control and therapeutic study. Am J Gastroenterol. 2003; 98: 625-629.
[62]	Poloni N, Vender S, Bolla E, et al. Gluten encephalopathy with psychiatric onset: Case report. Clin Practic Epidemiol Ment Health. 2009; 5: 16.
[63]	Kieslich M, Errazuriz G, Posselt HG, et al. Brain white matter lesions in celiac disease: A prospective study of 75 diet-treated patients. Pediatrics. 2001; 108: E21.
[64]	Jackson J R, Eaton W W, Cascella N G, et al. Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity. Psychiatr Q. 2012; 83: 91-102.
[65]	Hadjivassiliou M, Sanders D S, Grünewald R A, et al. Gluten sensitivity: from gut to brain. Lancet Neurol 2010; 9: 318-330.
[66]	Curione M, Barbato M, Di Biase L, et al. Prevalence of coeliac disease in idiopathic dilated cardiomyopathy. Lancet 1999; 354: 222e3.
[67]	Frustaci A, Cuoco L, Chimenti C, et al. Celiac disease associated with autoimmune myocarditis. Circulation 2002; 105: 2611e8.
[68]	Prati D, Bardella MT, Peracchi M, et al. High frequency of anti endomysial reactivity in candidates to heart transplant. Digest Liver Dis 2002; 34: 39e43.
[69]	Curione M, Barbato M, Viola F, et al. Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of gluten free diet on cardiac performance. Digest Liver Dis 2002; 34: 867e71.
[70]	Frustaci A, Cuoco L, Chimenti C, et al. Celiac Disease Associated With Autoimmune Myocarditis. Circulation. 2002; 105: 2611-2618.
[71]	Polat T B, Urganci N, Yalcin Y, et al. Cardiac functions in children with coeliac disease during follow-up: Insights from tissue Doppler imaging. Dig Liver Dis 2008; 40: 182-187.
[72]	Nota T, Faleschinia E, Tommasini A, et al. Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives. Eur Heart J 2003; 24, 1455-1461.
[73]	Ricardo Schmit T De Bem, Shirley Ramos Da Ro Sa Utiyama, Renato Mitsunori Nisihara, et al. Celiac Disease Prevalence in Brazilian Dilated Cardiomyopathy Patients. Dig Dis Sci. 2006; 51: 1016-1019.
[74]	Lodha A, Haran M, Hollander G, et al. Celiac Disease Associated with Dilated Cardiomyopathy. South Med J. 2009; 102: 1052-1054.
[75]	Milisavljević N, Cvetković M, Nikolić G, et al. Dilated Cardiomyopathy Associated with Celiac Disease: Case Report and Literature Review. Srp Arh Celok Lek. 2012; 140: 641-643.
[76]	Işikay S, Yilmaz K, Kilinç M. Celiac disease with pulmonary haemosiderosis and cardiomyopathy. BMJ Case Reports 2012.
[77]	Elfstrom P, Hamsten A, Montgomery S M, et al. Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease. J Intern Med 2007; 262: 545-554.
[78]	Vizzardi E, Lanzarotto F, Carabellese N, et al. Lack of association of coeliac disease with idiopathic and ischaemic dilated cardiomyopathies. Scand J Clin Lab Invest 2008; 68: 692-695.
[79]	Dawes PT, Atherton ST. Coeliac disease presenting as recurrent pericarditis. Lancet 1982; 8228: 1021-1022.
[80]	Faizallah R, Costello F C, Lee F I, et al. Adult celiac disease and recurrent pericarditis. Dig Dis Sci 1982; 27: 728-730.
[81]	Laine LA, Holt KM. Recurrent pericarditis and celiac disease. JAMA. 1984; 252: 3168.
[82]	Bardella M T, Fraquelli M, Quatrini M, et al. Prevalence of hypertransaminasemia in adult celiac patients and effect of gluten-free diet. Hepatology. 1995; 22: 833-836.
[83]	Sanders SDS, Ford AC. Meta-analysis: coeliac disease and hypertransaminasaemia. Alim Pharmacol Ther 2011; 34: 33-40.
[84]	Bardella MT, Vecchi M, Conte D, et al. Chronic unexplained hypertransaminasemiamay be caused by occult celiac disease. Hepatology. 1999; 29: 654-657.
[85]	Ludvigsson J F, Elfstrom P, Broom´e U, et al. Celiac disease and risk of liver disease: a general population-based study. Clin Gastroenterol Hepatol. 2007; 5: 63-69.
[86]	Sørensen H T, Thulstrup A M, Blomqvist P, et al. Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish and Swedish cohort data. Gut. 1999; 44: 736-738.
[87]	Lawson, West J, Aithal G P, et al. Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association. Aliment Pharmacol Ther. 2005; 21: 401-405.
[88]	Logan R F, Ferguson A, Finlayson N D, et al. Primary biliary cirrhosis and coeliac disease: an association? Lancet. 1978; 1: 230-233.
[89]	Kingham J G, Parker D R. The association between primary biliary cirrhosis and coeliac disease: a study of relative prevalences. Gut. 1998; 42: 120-122.
[90]	Lee F I, Murray S M, Norfolk D, et al. Primary biliary cirrhosis and coeliac disease. Lancet. 1978; 1: 713-714.
[91]	Lofgren J, Jarnerot G, Danielsson D, et al. Incidence and prevalence of primary biliary cirrhosis in a defined populationin Sweden. Scand J Gastroenterol. 1985; 20: 647-650.
[92]	Habior A, Lewartowska A, Orlowska J, et al. Association of coeliac disease with primary biliary cirrhosis in Poland. Eur J Gastroenterol Hepatol. 2003; 15: 159-164.
[93]	Bardella MT, Quatrini M, Zuin M, et al. Screening patients with celiac disease for primary biliary cirrhosis and vice versa. Am J Gastroenterol. 1997; 92: 1524-1526.
[94]	Vajro P, Paolella G, Maggiore G, et al. Metaanalysis: pediatric celiac disease, cryptogenic hypertransaminasemia, and autoimmune hepatitis. J Pediat Gastroenterol Nutr. 2013: 56: 663-670.
[95]	Villalta D, Girolami D, Bidoli E, et al. High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies. J Clin Lab Anal. 2005; 19: 6-10.
[96]	Volta U, de Franceschi L, Molinaro N, et al. Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Dig Dis Sci. 1998; 43: 2190-2195.
[97]	Lindberg J, Ahren C, Iwarson S. Intestinal villous atrophy in chronic active hepatitis. Scand J Gastroenterol. 1979; 14: 1015-1018.
[98]	Lindberg J, Ahren C, Jonsson J. Gluten-free diet in chronic active hepatitis associated with intestinal villous atrophy. Hepatogastroenterology. 1982; 29: 52-54.
[99]	di Biase R, Colecchia A, Scaioli E, et al. Autoimmune liver diseases in a paediatric population with coeliac disease—a 10- year single-centre experience. Alim Pharmacol Ther. 2010; 31: 253-260.
[100]	Nastasio S, Sciveres M, Riva S, et al. Celiac disease-associated autoimmune hepatitis in childhood: long-term response to treatment. J Pediatr Gastroenterol Nutr. 2013; 56: 671-674.
[101]	Volta U, Rodrigo L, Granito A, et al. Celiac disease in autoimmune cholestatic liver disorders. Am J Gastroenterol. 2002; 97: 2609-2613.
[102]	Brazier F, Delcenserie R, Sevestre H, et al. Primary sclerosing cholangitis and coeliac disease: beneficial effect of gluten-free diet on the liver. Eur J Gastroenterol Hepatol. 1994; 6: 183-186.
[103]	Cadah´ıa V, Rodrigo L, Fuentes D, et al. Celiac disease (CD), ulcerative colitis (UC), and primary sclerosing cholangitis (PSC) in one patient: a family study. Rev Esp Enferm Dig. 2005; 97: 907-913.
[104]	Reilly N R, Lebwohl B, Hultcrantz B, et al. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease. J Hepat 2015; 62: 1405-1411.
[105]	Iacono O L, Petta S, Venezia G, et al. Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease? Am J Gastroenterol. 2005; 100: 2472-2477.
[106]	Bardella MT, Valenti L, Pagliari C, et al. Searching for coeliac disease in patients with non-alcoholic fatty liver disease. Dig Liver Dis. 2004; 36: 333-336.
[107]	Pelaez-Luna M, Schmulson M, Robles-Diaz G. Intestinal involvement is not sufficient to explain hypertransaminasemia in celiac disease? Med Hypotheses. 2005; 65: 937-941.
[108]	Ince T, Kayadibi H, Soylu A, et al. Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients. Dig Dis Sci. 2008; 53: 1564-1572.
[109]	Bardella MT, Fraquelli M, Quatrini M, et al. Prevalence of hypertransaminasemia in adult celiac patients and effect of gluten-free diet. Hepatology. 1995; 22: 833-836.
[110]	Volta U, De Franceschi L, Lari F, et al. Coeliac disease hidden by cryptogenic hypertransaminasaemia. Lancet. 1998; 352: 26-29.
[111]	Zali M R, Rostami Nejad M, Rostami K, et al. liver complications in celiac disease. Hepat Mon.2011; 11: 333-341.
[112]	Bardella MT, Vecchi M, Conte D, et al. Chronic unexplained hypertransaminasemia may be caused by occult celiac disease. Hepatology. 1999; 29: 654-657.
[113]	Lindgren S, Sjoberg K, Eriksson S. Unsuspected coeliac disease in chronic ‘cryptogenic’ liver disease. Scand J Gastroenterol. 1994; 29: 661-664.
[114]	Ojetti V, Fini L, Dal Verme L Z, et al. Acute cryptogenic liver failure in an untreated coeliac patient: a case report. Eur J Gastroenterol Hepatol. 2005; 17: 1119-1121.
[115]	Tursi A. Celiac Disease and Viral B Hepatitis: Lessons for Clinical Practice. Hepat Mon. 2010; 10: 311-312.
[116]	Ouakaa-Kchaou A, Gargouri D, Kharrat J, et al. Relationship between Hepatitis B Virus Infection and Celiac Disease. Hepat Mon. 2010; 10: 313-314.
[117]	Cammarota G, Cuoco L, Cianci R, et al. Onset of coeliac disease during treatment with interferon for chronic hepatitis C. Lancet. 2000; 356: 1494-1495.
[118]	Butterworth J R, Cooper B T, Rosenberg W M, et al. The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease. Gastroenterology. 2002; 123: 444-449.
[119]	Morris WE, Jr. Hemochromatosis and celiac sprue. Case report. J Fla Med Assoc. 1993; 80: 243-245.
[120]	Freeman HJ. Iron deficiency anemia in celiac disease. World J Gastroenterol 2015; 21: 9233-9238.
[121]	Aggarwal S, Lebwohl B, Green P H R. Screening for celiac disease in average-risk and high-risk populations. Therap Adv Gastroenterol. 2012; 5: 37-47.
[122]	Greco D, Pisciotta M, Gambina F, et al. Celiac disease in subjects with type 1 diabetes mellitus: a prevalence study in western Sicily (Italy). Endocrine. 2013; 43: 108- 111.
[123]	Pham-Short, Donaghue K C, Ambler G, et al. Coeliac disease in type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration. Diabetic Med. 2012; 29: e.286-e.289.
[124]	Tiberti, Panimolle F, Bonamico M, et al. IgA antitransglutaminase autoantibodies at type 1 diabetes onset are less frequent in adult patients and are associated with a general celiac-specific lower immune response in comparison with nondiabetic celiac patients at diagnosis. Diabetes Care. 2012: 35: 2083-2085.
[125]	Ludvigsson J F, Ludvigsson J, Ekbom A, et al. Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care. 2006; 29: 2483-2488.
[126]	Leeds J S, Hopper A D, Hadjivassiliou M, et al. High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care. 2011; 34: 2158-2163.
[127]	Bakker S F, Tushuizen M E, von Blomberg M E, et al. Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications. Acta Diabetol. 2013; 50: 319-324.
[128]	Philip, R, Patidar P P, Saran S, et al. Endocrine manifestations of celiac disease. Indian J Endocrinol Metabol. 2012; 16: S506-508.
[129]	Collin P, Reunala T, Pukkala E, et al. Coeliac disease-associated disorders and survival. Gut. 1994; 35: 1215-1218.
[130]	Ch’ng C L, Biswas M, Benton A, et al. Prospective screening for coeliac disease in patients with Graves’ hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies. Clin Endocrinol. 2005; 62: 303-306.
[131]	Spadaccino C, Basso D, Chiarelli S, et al. Celiac disease in North Italian patients with autoimmune thyroid diseases. Autoimmunity. 2008; 41: 116-121.
[132]	Ch’ng L, Jones M K, Kingham J G C. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007; 5: 184-192.
[133]	Naiyer J, Shah J, Hernandez L, et al. Tissue transglutaminase antibodies in individuals with celiac disease bind to thyroid follicles and extracellular matrix and may contribute to thyroid dysfunction. Thyroid. 2008; 18: 1171-1178.
[134]	Ventura, Neri E, Ughi C, et al. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr. 2000; 137: 263-265.
[135]	Sategna-Guidetti, Volta U, Ciacci C, et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Gastroenterol. 2001; 96: 751-757.
[136]	O’Leary, Walsh C H, Wieneke P, et al. Coeliac disease and autoimmune Addison’s disease: a clinical pitfall. QJM. 2002; 95: 79-82.
[137]	Betterle, Lazzaratto F, Spadaccino A C,et al. Celiac disease in North Italian patients with autoimmune Addison’s disease. Eur J Endocrinol. 2006; 154: 275-279.
[138]	Hervonen K, Hakanen M, Kaukinen K, et al. First-degree relatives are frequently affected in coeliac disease and dermatitis herpetiformis. Scand J Gastroenterol. 2002; 37: 51-55.
[139]	Caproni M, Antiga E, Melani L, et al. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venereol. 2009; 23: 633-638.
[140]	Sugai, Smecuol E, Niveloni S, et al. Celiac disease serology in dermatitis herpetiformis.Which is the best option for detecting gluten sensitivity? Acta Gastroenterol Latinoam. 2006; 36: 197-201.
[141]	Ojetti V, Sanchez J A, Guerriero C, et al. High prevalence of celiac disease in psoriasis. Am J Gastroenterol. 2003; 98: 2574-2575.
[142]	Micha¨elsson, Gerd´en B, Hagforsen E, et al. Psoriasis patients with antibodies to gliadin can be improved by a gluten free diet. Br J Dermatol. 2000; 142: 44-51.
[143]	Addolorato, Parente A, de Lorenzi G, et al. Rapid regression of psoriasis in a coeliac patient after gluten-free diet: a case report and review of the literature. Digestion. 2003; 68: 9-12.
[144]	Abenavoli L, Proietti L, Leggio L, et al. Cutaneous manifestations in celiac disease. World J Gastroenterol. 2006; 12: 843-852.
[145]	Abenavoli L, Leggio L, Gasbarrini G, et al. Celiac disease and skin: psoriasis association. World J Gastroenterol. 2007; 13: 2138-2139.
[146]	Song M S, Farber D, Bitton A, et al. Dermatomyositis associated with celiac disease: response to a gluten-free diet. Can J Gastroenterol. 2006; 20: 433-435.
[147]	Iltanen S, Collin P, Korpela M, et al. Celiac disease and markers of celiac disease latency in patients with primary Sjogren’s syndrome. Am J Gastroenterol. 1999; 94: 1042-1046.
[148]	Szodoray P, Barta Z, Lakos G, et al. Coeliac disease in Sjogren’s syndrome a study of 111 Hungarian patients. Rheumatol Int. 2004; 24: 278-282.
[149]	Alvarez-Celorio M D, Angeles-Angeles A, Kraus A. Primary Sjogren’s syndrome and celiac disease: causal association or serendipity? J Clin Rheumatol. 2000; 6: 194-197.
[150]	Ludvigsson J F, Rubio-Tapia A, Chowdhary V, et al. Increased risk of Systemic Lupus Erythematosus in 29,000 patients with biopsy-verified celiac disease. J Rheumatol. 2012; 39: 1964-1970.
[151]	Freeman HJ. Adult celiac disease followed by onset of systemic lupus erythematosus. J Clin Gastroenterol. 2008; 42: 252-255.
[152]	Stagi S, Giani T, Simonini G, et al. Thyroid function, autoimmune thyroiditis and coeliac disease in juvenile idiopathic arthritis. Rheumatology (Oxford). 2005; 44: 517-520.
[153]	Alpigiani M G, Haupt R, Parodi S, et al. Coeliac disease in 108 patients with juvenile idiopathic arthritis: a 13-3ear follow-up study. Clin Exp Rheumatol. 2008; 26: 162.
[154]	Lepore L, Martelossi S, Pennesi M, et al. Prevalence of celiac disease in patients with juvenile chronic arthritis. J Pediatr. 1996; 129: 311-313.
[155]	Neuhausen S L, Steele L, Ryan S, et al. Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives. J Autoimmun. 2008; 31: 160-165.
[156]	Martins TGS, Costa ALFA, Oyamada MK, et al. Ophthalmologic manifestations of celiac disease. Int J Ophthalmol. 2016; 9: 159-162.
[157]	Maraini G, Hejtmancik J F, Shiels A, et al. Galactokinase gene mutations and age-related cataract. Lack of association in an Italian population. Mol Vis 2003; 9: 397-400.
[158]	Isaia G C, Casalis S, Grosso I, et al. Hypoparathyroidism and co-existing celiac disease. J Endocrinol Invest 2004; 27: 778-781.
[159]	Wang T J, Wu C K, Hu C C, et al. Increased risk of co-morbid eye disease in patients with chronic renal failure: a population-based study. Ophthalmic epidemiol. 2012; 19: 137-143.
[160]	Obeid M, Price J, Sun L, et al. Facial palsy and idiopathic intracranial hypertension in twins with cystic fibrosis and hypovitaminosis A. Pediatr Neurol 2011; 44: 150-152.
[161]	West K P Jr. Vitamin A deficiency disorders in children and women. Food Nutr Bull 2003; 24: S78-90.
[162]	Orbach H, Amitai N, Barzilai O, et al. Autoantibodyscreen in inflammatory myopathies high prevalence of antibodies to gliadin. Ann N Y Acad Sci 2009; 1173: 174-179.
[163]	Mollazadegan K, Kugelberg M, Tallstedt L, et al. Increased risk of uveitis in celiac disease: a nationwide cohort study. Br J ophthalmol 2012; 96: 857-861.
[164]	Choi, J M, Lebwohl B, Wang J, et al. Increased prevalence of celiac disease in patients with unexplained infertility in the United States: a prospective study. J Reprod Med. 2011; 56: 199-203.
[165]	Cummins AG, Roberts-Thomson IC. Prevalence of celiac disease in the Asia-Pacific region. J Gastroenterol Hepatol. 2009; 24: 1347-1351.
[166]	Janet MC, Benjamin L, Jeffrey W, et al. Prevalence of Celiac Disease in Patients with Unexplained Infertility in the United States: A Prospective Study. Journal Rep Med 2011; 56: 199-203.
[167]	Ludvigsson JF, Montgomery SM, Ekbom A. Celiac disease and risk of adverse fetal outcome: a population-based cohort study. Gastroenterology 2005; 129: 454-63.
[168]	Martinelli D, Fortunato F, Tafuri S, et al. Reproductive life disorders in Italian celiac women. A case-control study. BMC Gastroenterol 2010; 10: 89.
[169]	Aguiar FM, Melo SB, Galvao LC, et al. Serological testing for celiac disease in women with endometriosis. A pilot study. Clin Exp Obstet Gynecol 2009; 36: 23-25.
[170]	Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology. 2005; 128: S38-S46.
[171]	Lasa J S, zubiaurre I, soifer L O. Risk of infertility in patients with celiac disease: a meta-analysis of observational studies. Arq Gastroenterol. 2014; 51. 144-150.
[172]	Bianconcini, Mazzali F, Candini R, et al. Coeliac disease (familial) and sarcoidosis. Case report and review of literature. Minerva Med. 1994; 85: 541-553.
[173]	D’Ercole, Zullo A, Bragazzi M C, et al. Sarcoidosis and coeliac disease: do not forget the association. Inter Emerg Med. 2012; 7: S25.
[174]	Eliakim R, Heyman S, Kornberg A. Celiac disease and keratoconjunctivitis. Occurrence with thrombocytopenic purpura. Arch Inter Med. 1982; 142: 1037.
[175]	Ludvigsson F, Montgomery S M, Ekbom A. Risk of pancreatitis in 14,000 individuals with celiac disease. Clin Gastroenterol Hepatol. 2007; 5: 1347-1353.
[176]	Sadr-Azodi O, Sanders D S, Murray J A, et al. Patients with celiac disease have an increased risk for pancreatitis. Clin Gastroenterol Hepatol. 2012; 10: 1136-1142.
[177]	Green P H R, Yang J, Cheng J, et al. An association between microscopic colitis and celiac disease. Clin Gastroenterol Hepatol. 2009; 7: 1210-1216.
[178]	Stewart M, Andrews C N, Urbanski S, et al. The association of coeliac disease and microscopic colitis: a large population-based study. Alimen Pharmacol Ther. 2011; 33: 1340-1349.