*Autoimmune Diseases of the GI Tract Part I: Etiology and Pathophysiology DOI: http://dx.doi.org/10.5772/intechopen.106184*

at an earlier age and present more often with constipation, bloating, and anemia of iron deficiency than men [104, 105]. Gluten is the main etiology of CD. Gluten is a mixture of proteins found in grains of wheat (including gliadins and glutenins). CD can be caused by the presence of proteins from barley (hordeins) and rye (secalins). Among these, the gliadin peptides are the most immunogenic for CD [106]. Any case with malabsorption is defined as a classical disease and all other cases as nonclassical. Neoclassic CD manifests with largely extraintestinal symptoms, often monosymptomatic (e.g. iron deficiency anemia, premature metabolic bone disease, infertility, elevated transaminase levels) in the absence of clinical malabsorption. Over time, diarrhea has become less common at presentation, but it remains the most common gastrointestinal symptom [104]. Potential CD is a clinical term to describe suspected CD patients. Potential CD is characterized by normal small intestinal mucosa with positive CD serologic findings [107]. The diagnosis of CD remains challenging as it is estimated that currently only 20% of patients who have CD have been diagnosed [108]. CD cannot be diagnosed with one tool only. There is always a need for a combination of clinical features, serology, and histology are needed together to confirm the diagnosis [109]. In serological tests, patients should be on gluten-containing diets. Positivity in tests for Serum immunoglobulin A (IgA) anti-tissue transglutaminase antibody (anti-tTG-IgA) is widely accepted for the diagnosis but has low specificity. Serum immunoglobulin A (IgA) anti-tissue transglutaminase antibody (anti-tTG-IgA) are 100% specific but less sensitive [110–116]. Deamidated gliadin peptide (DGP) antibodies of the IgG class are advantageous for younger children [117]. All patients with suspected CD should undergo a duodenal biopsy. Regardless of CD serology results, duodenal biopsies should be performed in high-risk symptomatic patients [118]. There is a four out of five rule that is common in the diagnosis of CD. According to this rule, four of the following criteria are sufficient to establish CD diagnosis: (1) apparent and typical signs and symptoms of diarrhea and malabsorption, (2) positive serological tests of antibodies, (3) a patient with HLA-DQ2 or HLA-DQ8 positivity, (4) damage to the intestines, such as villous atrophy and lesions and (5) the response of the patient to GFD. This rule is important in the diagnosis of the diseases as many CD subtypes can be classified naming the non-classical CD which has no malabsorption or diarrhea, seronegative CD patients who do not show responses to serological antibodies, and a potential CD which has no damage to the intestines, and non-responsive CD who show no responses to GFD [109].
