Celiac Disease, sometimes referred to as Celiac Sprue or Gluten-Sensitive Enteropathy, is a disease characterized by an autoimmune reaction to a protein named gliaden. Gliaden is made when the body breaks down gluten, a protein commonly found in wheat and wheat products. Dutch pediatrician Willem Dicke first recognized the association between bread and cereal consumption and relapsing diarrhea in the early 1900s, and since then the disease has been increasing in incidence. Celiac disease can present in very different ways, ranging from a clinical picture of life-threatening malabsorption in a child to asymptomatic adults.
The prevalence of celiac disease in the general population is 0.4% to 1%, with 90-95% of individuals with celiac disease expressing HLA-DQ2 and 5 to 10% of individuals expressing HLA-DQ8. In the US and Europe, the prevalence is 3 to 13 per 1000 children. However, these numbers may underrepresent the incidence as recent studies suggest that for each case of celiac disease that is diagnosed there are fifty undiagnosed cases. The disease is more common in individuals with other autoimmune diseases, such as type 1 diabetes, when compared to the general population. Approximately 90% of individuals with diabetes and celiac disease are diagnosed with diabetes first, and develop celiac disease within a few years after being diagnosed with Type 1 diabetes. Further, up to 16% of individuals with Down syndrome and up to 10% of individuals with selective IgA deficiency are affected with celiac disease.
Celiac disease is a systemic, autoimmune disorder induced by the ingestion of gluten-containing proteins present in wheat, barley, rye, and (to a minor extent) oats. Zonulin, an intestinal peptide involved in the regulation of tight junctions, undergoes gluten induced up-regulation in individuals with celiac disease. This process then produces an increase in gut permeability that is characteristic of celiac disease. Gluten is deaminated by tissue transglutaminase and presented to T lymphocytes by the antigen presenting cells expressing the HLA genotype. Autoreactive T lymphocytes cause injury to the small bowel mucosa, skin, liver, joints, brain, and other organs. Non-genetic factors linked to celiac disease include age at introduction or dose of gluten and intestinal infections that produce gut hyperpermeability.
The classic presentation of individuals with active celiac disease include malabsorption/steatorrhea, constipation, abdominal pain and/or distention, irritability, and weight loss or failure to thrive. However, more recently patients are presenting less with a history of malabsorption and more commonly with nonspecific abdominal discomfort or extraintestinal symptoms. These extraintestinal forms include dermatitis herpetiformis (most common extraintestinal presentation with itchy bullous skin rash on the extensor surface of the limbs, trunk, and scalp), iron-deficiency anemia, hepatitis, hypertransaminasemia, short stature, pubertal delay, osteopenia, arthalgia, aphthous stomatitis, dental enamel defects, alopecia, infertility, depression, and cerebellar ataxia. Individuals with celiac disease may also be asymptomatic, also known as silent celiac disease. These individuals have serum IgA autoantibodies to tissue transglutaminase, histological lesions on small bowel biopsy, and celiac disease HLA genotypes. Although the evidence is not strong, there is a suggested association of silent celiac disease with nutritional deficiency, osteoporosis, lymphoma, and neurological disease. In the latent form of celiac disease, individuals have a normal small bowel biopsy, higher proportion of dividing epithelial crypt cells, and subtle abnormalities of the enterocytes. A large majority of these individuals have the HLA genotype associated with celiac disease and some may not have serum IgA autoantibodies to tissue transglutaminase.
Celiac disease is diagnosed by characteristic histologic changes on small intestinal biopsy (inflammation of the mucosa, villous atrophy, and crypt hyperplasia) of a symptomatic individual, and complete symptom resolution after the patient begins a gluten-free diet. Screening is recommended in children with clinical signs and symptoms of failure to thrive, persistent diarrhea, chronic constipation, dental enamel hypoplasia, idiopathic short stature, or significant pubertal delay, if these are not otherwise explained. IgA autoantibodies to tissue transglutaminase available in ELISA or radioassay are used to screen for celiac disease. There is also the highly specific IgA endomysial autoantibody (EMA) available as an immunofluorescence assay, but this has been largely replaced by IgA autoantibodies to tissue transglutaminase assays because of their higher sensitivities. Antigliadin and antireticulin serological test are no longer used because of poor performance and difficulties in use and standardization. Individuals with a recent diagnosis of type 1 diabetes should also be screened for celiac disease; if the results are negative and the patient is asymptomatic, they should be rescreened every third year.
Rish K. Pai, A practical approach to small bowel biopsy interpretation: Celiac disease and its mimics, Seminars in Diagnostic Pathology, Volume 31, Issue 2, March 2014, Pages 124-136, ISSN 0740-2570
The current treatment for celiac disease consists of a gluten free diet for the rest of the patient’s life. Treatment is recommended for all children who have presumptive celiac disease (patients with characteristic findings on intestinal biopsy and patients with dermatitis herpetiformis). It is not advised for patients with latent or potential celiac disease (children belonging in this category would have a positive tissue transglutaminase or IgA endomysial antibody, but a normal small bowel biopsy). IgA autoantibodies to tissue transglutaminase assays and anti-gliadin antibodies are more commonly used instead of small bowel biopsy as a marker of compliance and response to a gluten challenge. Further, because celiac disease is associated with hyposplenism, patients are at increased risk for invasive pneumococcal disease and should receive the pneumococcal vaccine.
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