Celiac disease

Celiac disease is defined as a T-cell–mediated inflammatory disease of predominantly small bowel triggered by gluten in the diet from wheat, rye, and barley in persons who are genetically susceptible. The consequences of chronic small bowel inflammation are mucosal atrophy and malabsorption of macronutrients, vitamins, and minerals.

The prevalence of celiac disease in the United States is 1 in 133 persons, the worldwide prevalence of celiac disease in whites is approximately 1%, and the rate of diagnosis appears to be increasing. Possible reasons  for its increasing prevalence include cultivation of wheat grains with higher gluten content, rotavirus infection that may increase intestinal permeability, and change in breast-feeding practices. Breast-feeding with the introduction of a small amount of gluten between 5 and 7 months of age may prevent or delay the onset of celiac disease in genetically susceptible infants. Celiac disease most commonly manifests at age 1 to 2 years, when gluten is first introduced into the diet, and in young adult life, but it can become evident at any age.

The main pathophysiologic consequences of chronic intestinal inflammation are villous atrophy and decreased surface area for nutrient absorption. Chronic inflammation may also down-regulate nutrient transport proteins in the intestinal epithelium. Pancreatic insufficiency caused by decreased release of secretin and cholecystokinin from atrophied duodenal epithelium and bacterial overgrowth may contribute to nutrient malabsorption.

Symptoms of celiac disease consists of diarrhea, gas and bloating, weight loss, fatigue, constipation, dyspepsia, unexplained hepatitis, neuropathy, ataxia, dental hypoplasia, infertility, burning, itching rash of dermatitis herpetiformis. Individuals with celiac disease may be obese on diagnosis. High-risk groups for the development of celiac disease include those with affected first-degree relatives, type 1 diabetes mellitus, autoimmune thyroid disease, irritable bowel syndrome, primary biliary cirrhosis, multiple sclerosis, and Down, William, and Turner syndromes. Most individuals with asymptomatic celiac disease have been identified by screening first-degree relatives of patients with celiac disease.

Celiac disease always affects the duodenum or proximal jejunum, but it can involve the entire small intestine. The nutrients malabsorbed and the clinical consequences depend on the site and extent of villous atrophy in the small intestine. Disease limited to the duodenum and proximal jejunum results in iron, folate, and calcium malabsorption because high-affinity transport mechanisms for their uptake are expressed only at these sites. The clinical consequences are iron deficiency or macrocytic anemia and bone mass loss. When celiac disease involves the entire small intestine, all macronutrients (carbohydrate, fat, protein) and vitamins and minerals are malabsorbed. The clinical consequences are diarrhea, gas and bloating caused by carbohydrate malabsorption, edema caused by hypoproteinemia, skeletal muscle and body weight loss, and manifestations of vitamin and mineral deficiencies. Vitamin B12 deficiency occurs in 10% to 40% of individuals with celiac disease, perhaps because of inflammation involving the distal ileum. Chronic diarrhea may cause zinc deficiency that contributes to diarrhea and slows mucosal healing. Patients with severe malabsorption may develop copper deficiency and neurologic abnormalities.

The most common findings in celiac disease are iron deficiency anemia and metabolic bone loss. In premenopausal women, iron deficiency anemia may be misattributed to menstrual losses or childbirth, thus delaying diagnosis. Celiac disease should be suspected when anemia in women or men does not correct with oral iron therapy or is associated with gastrointestinal symptoms. Low bone mass (osteopenia, osteoporosis) is found in up to 70% of adults with celiac disease and in 16% of children. Osteomalacia is less common. Adults with celiac disease have an approximately twofold higher risk of bone fracture than the normal population before and after treatment with a gluten-free diet. Whether bone mass loss is predominantly the result of calcium and vitamin D malabsorption or cytokine effect on bone from chronic intestinal inflammation is unclear. Men may have more severe bone loss than women; therefore, high-impact sports must be avoided until fracture risk has been assessed.

The only current treatment for celiac disease is a strict gluten-free diet. A secure diagnosis of celiac disease must be made before the diet is started. A gluten-free diet is complex and costly, and it may worsen quality of life, particularly in asymptomatic individuals. Once a diagnosis of celiac disease is made, six key elements (CELIAC) for management are recommended: consultation with a knowledgeable dietitian, education on the disease, a lifelong gluten-free diet, identification of nutritional deficiencies, access to a reputable support group, and continuous follow-up.

A gluten-free diet excludes the grains wheat, barley, and rye. Rice and corn grains are not toxic unless they are contaminated by wheat. A gluten-free diet is difficult to follow because gluten is ubiquitous in the Western diet and may be present in medications, over-the-counter drugs, and other items, such as communion wafers.

More than 70% of patients with celiac disease improve on a strict gluten-free diet within the first 2 weeks. Vitamin and mineral deficiencies, including iron deficiency and bone mass, often improve on a gluten-free diet alone. Children may reach peak bone mass if celiac disease is detected and treated early in life before puberty. Treatment with bisphosphonates may be required in patients with severe osteoporosis or older patients with celiac disease. Caution should be used with these agents early in disease or in patients with persistent inflammation because intestinal calcium absorption may not be adequate to maintain normal blood calcium levels. In patients with malabsorptive diarrhea, poor adherence to a gluten-free diet, or an unbalanced diet, a multiple vitamin with trace elements and minerals and a separate calcium supplement with vitamin D are recommended. The calcium with vitamin D supplement is also recommended in patients with lactose intolerance. Specific micronutrient supplements may be indicated, based on evidence of specific micronutrient deficiencies.

Individuals with celiac disease who do adhere to a gluten-free diet are at risk for the development of obesity resulting from improved intestinal absorption and the ingestion of carbohydrate-dense gluten-free products. Alternative grains, as well as fruits and vegetables, are ideal sources of fiber and micronutrients. Smaller portion size is recommended, as is increased exercise. Hyperlipidemia may result from increased absorption of cholesterol but may be beneficial. Certain vitamin deficiencies may develop because gluten-free products are particularly low in iron, folate, and calcium.

The most common cause of failure to improve on a glutenfree diet is ongoing occult or intentional gluten ingestion. Other causes of persistent gastrointestinal symptoms include lactose or fructose intolerance, other food allergies, a missed diagnosis, bacterial overgrowth, pancreatic insufficiency, or microscopic colitis.

Refractory celiac disease is defined as persistent gastrointestinal symptoms with ongoing villous atrophy despite a strict gluten-free diet for 6 to 12 months or after initially responding to a gluten-free diet. Severe malabsorptive diarrhea and weight loss are characteristic features. Autoimmune enteropathy, combined variable immunodeficiency, and secondary hypogammaglobulinemia have similar clinical presentations and may be misdiagnosed as refractory celiac disease. Treatment often requires aggressive nutrition support and steroids.

Individuals with symptomatic, undiagnosed celiac disease and those with poor dietary adherence have an increased mortality compared with the general population. In addition to complications caused by chronic malabsorption of essential nutrients, other risks of undiagnosed celiac disease include metabolic bone disease and the association with development of other autoimmune diseases such as type 1 diabetes mellitus and thyroiditis. Patients with celiac disease have a twofold to sixfold increased risk of non-Hodgkin lymphoma  and a smaller risk of esophageal cancer, melanoma, and gastrointestinal cancers when compared with the control populations.