Other autoimmune disorders
Liver diseaseIt is likely that common underlying genes are involved in some autoimmune disorders, although most autoimmune diseases are associated with several sequence variants. There could therefore be a common genetic link meaning those with coeliac disease are also genetically predisposed to developing certain other autoimmune diseases. Endocrine autoimmune disorders such as Type 1 diabetes and autoimmune thyroid disorders are most frequently associated with coeliac disease (1) .
The link between early diagnosis of coeliac disease and risk of other autoimmune disease
It has been hypothesised that the chance of developing other autoimmune diseases is increased when diagnosis of coeliac disease is delayed and therefore gluten exposure is prolonged (2) . However, this hypothesis was not supported in a study by Sategna Guidetti et al (3) and another large multi-centre study also found no connection to support the hypothesis particularly with regards thyroid disease (4) .
Thyroid disease
The link between coeliac disease and autoimmune thyroid disease is well established. It has been shown in studies that the prevalence of coeliac disease in patients with autoimmune thyroid disease is 4-15 times greater than in the general population. One study found that in a group of patients with coeliac disease 26.2% had autoimmune thyroid disease, compared to 10% of control subjects (5)
Graves' disease is the most common form of hyperthyroidism. About 30% of subjects with Graves' disease have a member of the immediate family who has also had an autoimmune condition. Ch'ng CL et al found that in a study of 111 patients with Grave's disease 4.5% had coeliac disease (6) . Patients with Hashimoto's disease have also been shown to be at increased risk of having coeliac disease (7) .
It is recommended that certain groups of patients at high risk are screened for thyroid disease i.e. following thyroid surgery and patients taking long term Lithium (8) . However, this is not currently recommended for patients with coeliac disease.
Liver disease
Abnormal liver biochemistry is common in untreated coeliac disease (9) suggesting that routine investigations for liver disease should include tests for coeliac disease such as anti-endomysial antibodies or tissue-transglutaminase antibodies (10) . This paper also emphasizes that false positive TTGA can occur in liver disease.
Autoimmune hepatitis (AIH) is a disorder where the liver is the target of the body's own autoimmune system. Prevalence of coeliac disease in people with autoimmune hepatitis has been found to be 6.4% (11) suggesting that screening of patients with AIH for coeliac disease should be considered. If left untreated, coeliac induced hepatitis may (rarely) progress to end-stage liver disease.
Primary biliary cirrhosis is an autoimmune disease that affects the biliary epithelial cells of the small bile ducts in the liver. Research has shown that there may be at least a threefold increase in the risk of primary biliary cirrhosis in people with coeliac disease (12) .
Treatment with a gluten-free diet in patients with both coeliac disease and liver disease can lead to prevention of hepatic failure even in severe cases where liver transplantation is being considered (13) .
Addison's disease
Addison's disease is an endocrine condition where there can be vague gastrointestinal symptoms due to adrenocortical insufficiency. Lifelong, continuous treatment with steroid replacement therapy is required. There are various causes of Addison's disease, but autoimmune adrenalitis now accounts for around 70% of all cases, and affects more women than men. Where Addison's disease is autoimmune, around half of those with the condition will develop another autoimmune disorder.
There is a similar immunogenetic background to coeliac disease and Addison's disease, with both diseases being associated with the DR3-DQ2 allele. However, this alone does not seem to explain the high incidence of one disease in a population with the other which research has shown to be between 7.9-12.2% (14,15).
Other autoimmune diseases which have been shown to have an increased incidence in a coeliac population are:
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There has been shown to be a moderately increased prevalence of coeliac disease in patients with sarcoidosis of approximately 4% (18).
References
1 Kaukinen et al. Celiac disease and autoimmune endocrinologic disorders. Digestive Diseases and Sciences1999;44:1428-1433
2 Ventura A et al. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology 1999;117:297-303
3 Sategna Guidetti C et al. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001;49:502-505.
4 Sategna Guidetti C et al. Prevalence of thyroid disorders in untreated adult coeliac disease patients and the effect of gluten withdrawal: an Italian multicentre study. American Journal of Gastroenterology 2001;96:751-7
5 Ansaldi N et al. Autoimmune thyroid disease and celiac disease in children. Journal of Paediatric Gastroenterology & Nutrition 2005;37(1):63-6
6 Ch'ng CL et al. Prospective screening for coeliac disease in patients with Graves' hyperthyroidism using anti-gliadin and tissue transglutaminase antibodies. Clinical Endocrinology 2005;62(3):303-6
7 Valentino R et al. Markers of potential coeliac disease in patients with Hashimoto's thyroiditis. European Journal of Endocrinology 2002;146:479-483
8 Vanderpump M et al. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism. BMJ 1996;313:539-544
9 Dickey W et al. Liver abnormalities associated with celiac sprue: how common are they, what is their significance, and what do we do about them? Journal of Clinical Gastroenterology 1995;20:290-2
10 Lo Iacono O et al. Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease? American Journal of Gastroenterology 2005;100:2472-7.
11 Villaita D et al. High Prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue transglutaminase autoantibodies. Journal of Clinical Laboratory Analysis 2005;19(1):6-10
12 Lawson A et al. Autoimmune cholestatic liver disease in people with coeliac disease: a population based study of their association. Alimentary Pharmacology and Therapeutics 2005;21(4):401-5
13 Kaukinen K et al. Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure. Gastroenterology 2002;122(4):881-8
14 Myhre AG et al. High frequency of coeliac disease among patients with autoimmune adrenocortical failure. Scandinavian Journal of Gastroenterology 2003;38(5):511-5
15 O'Leary C et al. Coeliac disease and autoimmune Addison's disease: a clinical pitfall. Q J Med 2002;95:79-82
16 Szodoray P et al. Coeliac disease in Sjogren's syndrome - a study of 111 Hungarian patients. Rheumatology International 2004;24(5):278-82
17 Luft LM et al. Autoantibodies to tissue transglutaminase in Sjogren's syndrome and related rheumatic diseases. Journal of Rheumatology 2003;30(12):2613-9
18 Rutherford RM et al. Prevalence of coeliac disease in patients with sarcoidosis. European Journal of Gastroenterology and Hepatology. 2004;16(9):911-5.
