*5.1.1 Difficulties in following a gluten-free diet: transgressions*

Although adherence to GFD is the cornerstone of the treatment of patients with CD, there are conditions that prevent it from being carried out and mean that a significant percentage of patients with CD do not adhere and commit voluntary or involuntary transgressions [10]. Among the conditions that can prevent the GFD monitoring, we highlight the high economic cost of gluten-free products, which are not accessible to a large number of people with CD. Another factor to highlight that can favor its involuntary intake is the ubiquity of gluten in a high percentage of manufactured products since many of the foods that are marketed contain gluten from wheat, barley, rye, or oats, including those that intervene only as a thickener or binder. In fact, several studies carried out to determine the gluten content in natural (unprocessed) gluten-free foods or in foods labeled gluten-free reveal relatively

### *Celiac Disease, Management, and Follow-Up DOI: http://dx.doi.org/10.5772/intechopen.104652*

high contamination rates, present in 9–22% of the samples analyzed [54–56]. In addition, many products contain hidden gluten, mainly due to cross-contamination with other gluten-containing foods that are processed or stored in the same place. The risk that these foods pose for patients with CD makes rigorous control of gluten content convenient [57]. Therefore, accurate detection and quantification of gluten in food are essential [10]. The Codex Alimentarius [58] has established that a food classified as "gluten-free" should not exceed 20 mg of gluten per kg of food, that is, 20 parts per million (ppm). Currently, several methods are used for the detection and quantification of gluten in foods. Enzyme-Linked ImmunoSorbent Assays (ELISAs) are the most widely used methods, as they are sensitive, rapid, and relatively easy to perform. Most commercial ELISAs use monoclonal antibodies (moAbs) such as R5 and G12 [59–64]. Other methods, such as the Polymerase Chain Reaction (PCR), developed mainly for research, are far from being able to replace ELISA, as they are not suitable for the detection of gluten in highly processed or hydrolyzed samples due to DNA degradation. Lastly, liquid chromatography/mass spectrometry methods require expensive equipment and expertise [65].

All the factors described above cause nonadherence to GFD among patients with CD. Recent studies have indicated that inadvertent gluten ingestion occurs more frequently than intentional ingestion, and gluten contamination in naturally gluten-free foods is likely to be one of the most important factors in inadvertent nonadherence [66]. Other investigations based on the study of intestinal biopsies of patients with CD on GFD for more than 2 years have suggested that transgressions are relatively frequent, detecting a lack of recovery of the intestinal villi in 36–55% of the population studied [67–69]. These inadvertent or intentional violations are the main reason for uncontrolled CD in adult patients with CD [70]. Likewise, there is a small percentage of patients with CD (approximately 0.3–10%) who do not respond to GFD and have persistent symptoms of malabsorption and intestinal villi atrophy, which is known as refractory CD (RCD) [7, 71–74].
