Thursday, January 27, 2011

Gluten's Comorbid Influence

According to an exhaustive review that recently appeared in Expert Review of Gastroenterology and Hepatology, celiac disease is now one of the most common chronic diseases encountered in the Western world. Since it is so common, much comorbidity will occur either as associations or simply by chance, or as complications of the disorder.

Autoimmune diseases constitute clinically important associations, of which Type 1 diabetes mellitus and thyroid disorders are the most important. Several liver disorders are also associated. The most common malignant complication of celiac disease is an increased risk of lymphoma by approximately fivefold. The increase of fracture risk is modest. Although neurological and psychiatric conditions affect celiac patients, no disorder have been identified. Reproductive problems occur as well. It is important that these co-morbidities are recognized because if not, symptoms will be falsely attributed to deliberate or inadvertent ingestion of gluten, rather than prompt a search for a second diagnosis. Furthermore, in a patient with an established diagnosis that is considered falsely to account for the whole clinical picture, celiac disease is likely to remain undetected. Note: there were many diseases the researchers alluded to but we did list because the "research" was not substantive to warrant a true connection to celiac. It is the research yet to be done that we really want to see because in our opinion, it will blow public health educators away. What you read below is just the tip of the iceberg.

Detailed Breakdown:

Autoimmune 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. 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. 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 and in practice, screening is being increasingly undertaken.

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
Thyroid disease was three-times more likely to occur in adults who were newly diagnosed with celiac disease in comparison with healthy controls. Using a study done with the Swedish In-Patient Registry, celiac disease was found to be associated with hypothyroidism, thyroiditis, and hyperthyroidism. 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. Autoimmune thyroiditis may arise when children are on a gluten-free diet, which suggests that thyroid disturbance is independent of the presence of gluten. However, gluten withdrawal in adults, may normalize thyroid tests in those with subclinical hypothyroidism. 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 observed a fourfold increased risk of having an autoimmune liver disease for primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in people with celiac disease in comparison with general population controls. A 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 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 observed an 11-fold increased risk of Addison's disease developing in those with celiac disease. 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. The prevalence of celiac disease in patients with psoriasis was increased threefold in comparison with age- and sex-matched controls. Sjogren's syndrome, primary hyperparathyroidism, hypoparathyroidism, hypopituitarism and systemic lupus erythematosus have all been described in association with celiac disease, but the body of research is scant as of now.

Diagnosed celiac disease has been traditionally linked with greatly increased risks of lymphoma and other malignancies. As larger, population-based studies have appeared, more modest although still increased risks are suggested, with the risk of lymphoma increased at least fivefold with a 30% increased risk of any malignancy in people with celiac disease in comparison with the general population. These larger studies have also supported an increased risk of small intestinal adenocarcinoma, esophageal cancer and oropharyngeal cancer in diagnosed celiac disease.

Refractory Celiac Disease
Nonresponsive celiac disease (NRCD) has historically been described as a failure to respond to treatment with a gluten-free diet and can be described as primary NRCD (the celiac never responds to a gluten-free diet) or secondary NRCD (response is lost after initial improvement with recurrence of symptoms after 1 year). Depending on study design and study population selected, the prevalence of NRCD is approximately 15–30%. The majority of cases of NRCD are probably related to continued gluten exposure: inadvertent ingestion of small but immunologically significant amounts or nonadherence. Having confirmed the index diagnosis of celiac disease holds true and established adherence to a gluten-free diet, other causes of symptoms need excluding. This includes conditions associated with celiac disease that are amenable to treatment, such as microscopic colitis, pancreatic insufficiency, irritable bowel syndrome, small bowel bacterial overgrowth, thyroid dysfunction and lactose intolerance. Note: from what we see, these are often people who cannot handle cornstarch that is prevalent in so many gluten-free products.

Metabolic Bone Disease & Fracture Risk
There is a modest increase in the risk of fracture in celiac disease. Studies suggest there is a moderate reduction of BMD in untreated celiac disease, with weighted mean Z scores at the lumbar spine and hip. Studies have also suggested that a gluten-free diet improves BMD in people with symptomatic celiac disease.

Neurological Conditions

It might be expected that those with a chronic condition, especially if the diagnosis is delayed and the treatment is a restrictive diet that limits social interaction, would result in depression. There is no doubt that depression in celiac disease can be severe to the point where patients may attempt and succeed in suicide. A gluten-free diet improves depression and anxiety in some but not all cases. As well as a gluten-free diet, vitamin B supplementation is recommended to improve mood. Impaired availability of tryptophan may be important in depressive and behavioral disorders in celiac disease.

Migraine may occur in celiac disease and improve or be cured by a gluten-free diet.

Reproductive Problems
Previous studies have raised concern regarding reduced fertility and increased adverse pregnancy-related outcomes in women with celiac disease. Some authors have accepted that infertility is a complication of celiac disease. Reported associations between celiac disease and miscarriage have also added to the concern. Women with untreated celiac disease are at greater risk of delivering small babies than those without celiac disease.

Risk of Infection in Celiac Disease
People with celiac disease have a sevenfold increased risk of death from septicemia, and threefold increased risk of death from infection and pneumonia in comparison with general population controls.

Gastrointestinal Disorders
Irritable bowel syndrome is common, but only a small percentage of patients are referred to hospital for evaluation. Symptoms such as abdominal bloating, diarrhea and constipation are common to irritable bowel syndrome and celiac disease, so the two conditions are easily confused. A search for celiac disease in irritable bowel syndrome can be supported, because in a recent study of individuals with irritable bowel syndrome, the prevalence of celiac disease was increased fourfold. For those symptoms due to celiac disease, a gluten-free diet would be expected to be effective. However, a gluten-free diet may still be beneficial in those with symptoms owing to irritable bowel syndrome in the absence of celiac disease.

Celiac disease may occur in association with ulcerative colitis and Crohn's disease. Furthermore, these three disorders can be present in different members of the same family. The prevalence of ulcerative colitis and Crohn's disease was found significantly higher in celiac disease than in the general population. In 90% of instances, celiac disease is the first diagnosis to be made.

Other Various Disorders
Celiac disease was associated with an increased risk of subsequent pancreatitis.

Celiac disease and noncirrhotic intrahepatic hypertension may occur together, but the reasons are unknown.

Enamel defects and recurrent aphthous ulcers are observed in patients with celiac disease.

The prevalence of celiac disease is increased in some genetic disorders such as Down syndrome, Williams syndrome, and Turner syndrome.

In patients with cystic fibrosis, the prevalence of celiac disease is three-times greater than the general prevalence of celiac disease. Symptoms due to celiac disease will be alleviated by a gluten-free diet, so making this diagnosis is important and screening those with cystic fibrosis is recommended.

Although most, if not all, people with dermatitis herpetiformis have gluten-sensitive enteropathy.

Finally, an The American Journal of Gastroenterology study published this week states that periodic biopsy testing to monitor mucosal intestinal recovery is warranted in celiac patients on gluten-free diets. Poor compliance with the diet, severe villi atrophy, among other factors can impede intestinal mucosal recovery in a significant percentage of celiac patients. The study found that a lack of mucosal recovery increases the rate of all-cause mortality.

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