Risk of Morbidity in Contemporary Celiac Disease

Nina R Lewis; Geoffrey KT Holmes

Disclosures

Expert Rev Gastroenterol Hepatol. 2010;4(6):767-780. 

In This Article

Autoimmune Disorders

Clinically diagnosed celiac disease is associated with a number of autoimmune diseases, although it is possible that in many instances ascertainment bias may be contributing to the associations reported. Nonetheless, recent screening studies have demonstrated an increased prevalence of celiac disease in autoimmune disorders including Type 1 diabetes, thyroid and liver disorders.

Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is the most common and best-researched association. The diagnosis of celiac disease may precede that of diabetes, but in approximately 90% of patients, diabetes is diagnosed first.[23] Screening studies have revealed that the prevalence among children with diabetes is approximately 4.5% (26 studies),[24] but higher figures of 12.3%[25] and 10%[26] have been reported. In adults, the prevalence is approximately 3.5% (eight studies).[27] Of the 33 children with diabetes and celiac disease, all interviewed by a doctor, 28 (85%) had symptoms or biochemical features of celiac disease, and in four children, the symptoms were recognized retrospectively after a gluten-free diet was initiated.[25] In another study, 13 out of 17 children (76%) had gastrointestinal symptoms.[28]

A gluten-free diet has been shown to be effective in reversing ill health due to celiac disease in these patients, and improvement in height, weight and a reduction in hypoglycemic episodes has been shown in some series, but not all.[25,28,29] Even those who regard themselves as asymptomatic should be offered a gluten-free diet because it may have unexpected benefits, and if it does not, it is likely to be abandoned by the patients themselves.

Whether or not to screen patients with diabetes for the presence of celiac disease remains controversial, but a case can be made for a screening program when the high frequency of the association is considered, that patients may have symptoms and a gluten-free diet can improve health. There is support for screening children and adolescents with Type 1 diabetes[25,26,30] and in practice, screening is being increasingly undertaken.[31] What the interval between screening tests should be has been debated, but since diabetics are kept under annual review, screening is easily arranged. Most diagnoses of celiac disease were made in one study within 2–3 years of the diagnosis of diabetes, with a cumulative prevalence of 10% at 5 years.[26] Adult patients, parents of children and, where possible, children themselves, should be fully involved at all stages of the screening, diagnostic and treatment process, and be helped by sympathetic doctors and dieticians skilled in the gluten-free diet.[24,27]

From available evidence, one could argue that screening of those with Type 1 diabetes for celiac disease is worthwhile, and that a gluten-free diet should be offered to all those who are positive.

Thyroid Disease

Although the study was limited such as by selection bias, on the basis of thyroid biochemistry, 4% (95% CI: 1.8–7.6) of celiac patients had subclinical hypothyroidism, 12% (95% CI: 8.0–16.0) had overt hypothyroidism and 2% (95% CI: 0.8–5.0) had Graves' disease in patients who had attended an outpatient clinic (n = 184) in The Netherlands.[32] Conversely, 5% (95% CI: 0.7–8.9) of patients attending the outpatient clinic with Hashimoto's thyroiditis were also diagnosed with celiac disease.[32] Lacking general population controls as a comparator in the study, the authors compared their observed prevalence of thyroid disease to that reported in published studies based on American cohorts with the prevalence of overt hypothyroidism that was at least ten-times more common in celiacs than in the general population comparator, while Graves' disease had approximately the same frequency. Thyroid disease was three-times more likely to occur in adults who were newly diagnosed with celiac disease in comparison with controls (healthy volunteers such as medical staff, blood donors and patients attending for endoscopy).[33] Using the Swedish In-Patient Registry, celiac disease was found to be associated with hypothyroidism (hazard ratio [HR]: 4.4 [95% CI: 3.4–5.6]), thyroiditis (HR: 3.6 [95% CI: 1.9–6.7]) and hyperthyroidism (HR: 2.9 [95% CI: 2.0–4.2]).[34] The highest risk estimates for thyroid disease were observed in children, which is in keeping with other studies that raised the issue of whether children with celiac disease should be screened for thyroid disease.[35,36] Autoimmune thyroiditis may arise when children are on a gluten-free diet, which suggests that thyroid disturbance is independent of the presence of gluten.[35] However, gluten withdrawal in adults, may normalize thyroid tests in those with subclinical hypothyroidism.[33]

It is important to be aware of these associations, because those with celiac disease may have symptoms such as weight loss, lethargy and diarrhea attributed to celiac disease in relapse because of lax adherence to a gluten-free diet, rather than to the presence of thyroid disease.

Liver Disease

A number of liver conditions have been reported to be associated with celiac disease. Recent population-based data using the General Practice Research Database and Swedish In-Patient Registry observed a fourfold increased risk of having an autoimmune liver disease (HR: 3.6 [95% CI: 1.5–9.0] for primary biliary cirrhosis; HR: 4.1 [95% CI: 2.1–8.0] for primary sclerosing cholangitis and HR: 4.4 [95% CI: 1.6–12.0] for autoimmune hepatitis) in people with celiac disease in comparison with general population controls.[37,38] In contrast to the reported 0.2% prevalence of autoimmune liver disease in celiac disease, in a recent population-based cohort, the most common hepatic injury to affect celiacs is isolated hypertransaminasemia, which was observed to affect 10% of adults newly diagnosed with celiac disease.[39] The observed hypertransaminasemia has been coined 'gluten' or 'celiac hepatitis'.[40] The hepatic injury is reputed to be characterized by the absence of serum autoantibodies (other than endomysial and tissue transglutaminase antibodies), elevated transaminases and the presence of mild lobular and portal tract inflammation and steatosis that is reversible after treatment with a gluten-free diet.[40] With significant reduction in transaminases and the transaminase result normalizing in 86% of those with an abnormal result at diagnosis of celiac disease following a year of treatment with a gluten-free diet,[39] it suggests that investigations for liver disease should only be initiated in those celiacs with persistent hypertransaminasemia despite gluten-free diet or if otherwise indicated.

Other Autoimmune Diseases

Recent population-based data using the Swedish In-Patient Registry observed an 11-fold increased risk (HR: 11.4 [95% CI: 4.4–29.6]) of Addison's disease developing in those with celiac disease.[41] Conversely, those with established Addison's disease had a ninefold increased risk of developing celiac disease. A positive association between celiac disease and immune thrombocytopenic purpura has been found.[42] The prevalence of celiac disease in patients with psoriasis was increased threefold in comparison with age- and sex-matched controls (odds ratio [OR]: 2.7 [95% CI: 1.7–4.5]).[43] The prevalence of rheumatoid arthritis is not increased in celiac disease.[44] Sjogren's syndrome,[45] primary hyperparathyroidism,[46] hypoparathyroidism,[47] hypopituitarism[48] and systemic lupus erythematosus[49,50] have all been described in association with celiac disease, but usually in a small series or case reports.

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