Background: Celiac disease (CD) is chronic small bowel inflammation with villous atrophy, consequently, an immune-mediated disorder triggered by ingesting Gluten in wheat, barley, and rye in genetically susceptible individuals.

Aims: Summarize the fundamental principles for managing the diet of patients with CD. This Mini-Review using relevant articles in PubMed's online databases followed the medical keywords Celiac Disease, Gluten, gluten-free diet, nutritional approach, and diet adherence. The institution's Ethics Committee has waived the need to review the ethical aspects of this text. The cornerstone of the treatment is the lifelong adherence to a Gluten-Free Diet (GFD). This dietary regimen, which forms the basis of the patient's treatment, requires eliminating all food components containing Gluten and its derivatives from the diet. However, the treatment approach has changed from focusing on food avoidance to a wide-ranging evaluation of the various factors influencing the dietary choices in the patient's life. The Global Approach to the Follow-up of Celiac Disease is based on 1) control of symptomatology and dietary adherence; 2) improving emotional and social wellness in treating CD patients, with the active involvement of a psychologist; and 3) ensuring successful education of both the child and the family about its management. Indeed, the impact of CD extends beyond the patient and affects the well-being of caregivers and 4) evaluate socioeconomic burden, considering that Gluten-free food products remain significantly more expensive than gluten-containing equivalents with variable availability. So, the GFD is the primary treatment for CD, and difficulties in managing the Disease can lead to impaired Quality of Life.

In conclusion, strict adherence to the GFD is imperative, requiring a multidisciplinary team involving physicians, dietitians, and psychologists on a regular visit schedule to assess dietary adherence and avoid long-term complications.

 Keywords: celiac disease, gluten, gluten free diet, nutritional approach, diet adherence

CD, celiac disease; CDAT, coeliac dietary adherence test; FDA, food and drug administration; GFD, gluten-free diet; SDE, standardised dietitian evaluation; SGA, subjective global assessment; tTG, tissue transglutaminase

Background: Hippocrates' famous quote, "Let food be thy medicine and medicine be thy food," has a profound historical significance. It reminds us that since ancient Greek and Roman times, 'disease' has been used to denote physical imbalance, and food and diet have been considered crucial to restoring this imbalance. CD is chronic small bowel inflammation with villous atrophy, consequently an immune-mediated disorder. It is generated by Gluten, which is part of the composition of the wheat, barley, and rye and their by-products in genetically susceptible children/adults carrying the HLA-DQ2 and HLA-DQ8 gene, with the highest risk observed in individuals who are homozygous for DQ2. The estimated 1% prevalence occurs more in children than in adults.^{1, 2} An increasing prevalence has been observed in the previous thirty years.³ Early diagnosis of CD is based on clinical and serological tests, villous atrophy on duodenal histology, and the positive response to a GFD. The early diagnosis empowers healthcare professionals to intervene effectively and improve patient outcomes. In pediatric patients, CD is associated with gastrointestinal clinical symptoms (diarrhea, steatorrhea, flatulence, abdominal pain, and distension and malabsorption-associated complications) and extraintestinal symptoms (mainly malnutrition, failure to thrive, anemia). The clinical symptoms correlate with histological findings and Anti-Tissue Transglutaminase Antibodies.^4–7

Aims: This mini-review will explore the basic principles of the nutritional approach in Celiac Disease (CD), focusing on the specific dietary interventions that offer promising benefits of a Gluten-Free Diet (GFD). This Mini-Review using relevant articles in PubMed's online databases followed the medical keywords Celiac Disease, Gluten, gluten-free diet, nutritional approach, and diet adherence. The institution's Ethics Committee has waived the need to review the ethical aspects of this text

Gluten and the development of celiac disease

Table 1 displays the main components of the development of CD. The central environmental factor is Gluten, a mixture of prolamin proteins composed of gliadins and glutenins. They are predominantly found in wheat but in other cereals with specific designations: barley (hordeins), rye (secalins), and oats (avenins). They are highly resistant to degradation and activate the immune system in patients with a genetic predisposition.⁸ Due to increased intestinal permeability, peptides interact with antigen-presenting cells in the lamina propria. However, oats consumption seems safe for most celiacs.^4–6,9

Table 1 Three-point continuum of nutrition economics.

CD encompasses gastrointestinal, musculoskeletal, dermatological, reproductive, cardiovascular, endocrine, and neurological symptoms. These symptoms can be attributed to both intestinal malabsorption and immune activation. The continuing effects of villous atrophy and inflammation result in malnutrition. However, managing CD through a GFD prevents severe nutritional consequences and significantly improves the patient's Quality of Life.¹⁰

Deficiency of minerals and vitamin D

At diagnosis, the most prevalent mineral, higher in adults than children and comprising over half of the CD patients, is iron deficiency anemia.^11–14 Indeed, the duodenum is the coexistence of villous atrophy and the maximum site of iron absorption, calcium, and Vitamin D. Accordingly, Vitamin D is involved in the hormonal regulation of bone remodeling and calcium absorption. It is of concern, considering the probable impaired bone health. Zinc deficiency is prevalent in untreated and treated patients, mainly related to malabsorption, and is partially responsible for skin lesions.^10,15 Also, Copper deficiency is related to anemia, thrombocytopenia, and neurologic impairment.^16–18 Therefore, Pediatric patients with CD are at risk of short stature, impaired peak bone mass achievement, and delay of puberty.^8,19

Treatment

Gluten-free diet

The basis of CD treatment is permanent adherence to a GFD that excludes food and non-food products from wheat, rye, and barley. This dietary regimen, which forms the basis of the patient's treatment,²⁰ stimulates the Immune system when Gluten is ingested, making strict adherence to a GFD critical. The significant improvement in symptoms and the promotion of healing of the duodenal mucosa observed with a GFD underscore its efficacy and the importance of patient supervision to ensure adherence and promote healing.^5,21–23

Dietary counseling

The treatment approach has changed from focusing on food avoidance to evaluating the various factors influencing the dietary choices in the patient's life. Dietary and behavioral counseling should accurately assess the individual's skill to implement the GFD. It is important to note that diet restriction and compliance can be challenging for many patients. The dietary counseling model must address the complex aspects of life, considering the effects of GFD on physical, emotional, and social well-being. The dietitian should identify barriers and motivators in their life and assist in developing strategies to navigate these situations.^{24, 25} Table 2 displays the primary approach of patients with CD, and Table 3 presents Education (Discuss, Ensure, Explain, Encourage, Give, Highlight, Provide) about the GFD.

The primary nutritional approach in pediatric celiac disease

The four different viewpoints on the primary nutritional approach in CD, brilliantly explained by Perez-Junkera et al.,²⁶ are briefly presented below:

Regular observation of symptoms and adherence to a GFD

The initial assessment requests medical conditions, weight, physical activity, diet, allergies, food intolerances, nutrient deficiencies, and the individual's knowledge of CD. Food obtaining, preparation, food preparation facilities, and cooking skills must be assessed individually before beginning patient education. So, read food labels and understand the importance of avoiding gluten exposure.²⁶ On the contrary, nonadherence. to diet can aggravate intestinal damage, sustain symptoms, and raise the risk of small intestinal cancer.²⁵

Routine to be adopted at each visit

Clinical signs/symptoms valuation and dietetic interview are the basis associated with laboratory exams (Hemogram, serum electrolytes, ferritin, vitamins (D and B12), alkaline phosphate, aspartate aminotransferase, and alanine aminotransferase levels.²⁵ For monitoring GFD adherence, stool and urine markers and measurement of ELISA- IgA antibodies to Tissue Transglutaminase (tTG) are essential.^4,5,27 Hence, a follow-up biopsy may be performed in patients diagnosed at an older age and with severe initial presentations.

Dietary adherence

Strict adherence to a GFD is difficult, considering that many processed foods can hide Gluten. Dietitian assessment, education, and counseling are the cornerstones of dietary management and require close follow-up. The basic actions would be monitoring dietary history, investigating nutritional deficiencies, and evaluating body composition. Explore gluten transgressions and educate for deficiency of knowledge about reading labels and the risk of cross-contamination.

Tools to evaluate the adherence to a GFD

Combining questionnaires with other procedures expands the assessment of dietary adherence, and two main tests have been proposed to measure GFD.

1. The Standardised Dietitian Evaluation (SDE). It involves a skilled dietitian assessing gluten exposure and adherence and analyzing a 3-day food record. Consequently, it is time-consuming.²⁸
2. The Coeliac Dietary Adherence Test (CDAT) is a 7-item survey identifying poor adherence. Higher scores denote worse GFD adherence.²⁹

Refractory celiac disease

The refractory CD is characterized by persistent symptomatology despite adherence to GFD for 12 months. Suppose suspected incorrect diagnoses; the first step is to revise the serology, histology, and HLA typing results. Once the diagnosis is confirmed, gluten inadvertent exposure should be re-evaluated.^30,31 The duodenal biopsies may classify patients into First) If persistent symptoms with normal duodenal histology, consider CD in remission or explore other causes. Second) Persistent symptoms and villous atrophy are considered slow responses to GFD, cross-contamination, small amounts of Gluten, or other reasons for villous atrophy.^32,33

The nutritional status evaluation

Assuming the specific nutritional needs of patients with CD, a nutrition assessment is recommended to provide a primary approach to evaluating dietary intake and nutrient deficiencies and determining the severity of malnutrition. The CD patient presents malabsorption, resulting in multiple nutritional deficiencies.³⁴ Screening for malnutrition needs to be performed carefully at each visit. The Subjective Global Assessment (SGA) is the most utilized tool for evaluating intake, weight, functional status, and body composition, allocating into three malnutrition grades: no malnutrition (SGA A), mild/moderate (SGA B), and severe (SGA C).³⁵

Psychological primary approach

Improving emotional and social well-being is vital in approaching CD patients, considering the risk of depression, anxiety, stress, and fatigue with consequent impairment on Health-Related Quality of Life. In addition, eating disorders such as limitations when eating outdoors. GFD "extreme vigilance" may feel annoyance, distress, disgrace, and sadness. The impact of CD extends beyond the patient and affects the well-being of caregivers and the wider family. Indeed, the family must also be considered when educating and supporting these patients. The psychologist must assist in promoting adherence to the GFD. One of the critical strategies is the provision of coping skills, such as social skills, acceptance, and control.

Primary social approach and education

GFD is connected with a substantial socioeconomic burden. Gluten-free food products are more expensive than regular products, compromising the adherence to a GFD. So, providing patients with education and treatment information is crucial. Indeed, social limits when eating out, participating in social events, or traveling could impact their psychological well-being. Traveling when no GFD food is available is challenging. In addition, the parents' and general population's knowledge and consciousness about CD are low. Promoting Celiac patients' integration in the CD Society is essential to encourage social inclusion.³⁶

Labeling gluten-free food and cross-contamination

The labels of food products must be routinely checked to guarantee complete gluten-free products. Foods known not to contain Gluten may present gluten traces resulting from cross-contamination.³⁷ Thus, cross-contamination might occur from planting to the final preparation and lead to apprehension. Celiac patients are at risk at home and eating outside the home. Shared kitchen utensils and equipment may not increase gluten cross-contamination if appropriate directions are followed.^38,39

Alternative non-dietary treatments for celiac disease

Table 4 presents the current and future alternatives proposed for the non-dietary treatment of CD, according to Wessels et al.⁴⁰

Prevention

Prevention could be achieved based on three points.

1. Primary strategies such as avoiding disease development are impossible (until now). There is no evidence that the time of breastfeeding or the time of introducing Gluten into the infant's diet has an impact on the risk of developing CD.⁴
2. Secondary: serological screening of high-risk groups (first-degree relatives, patients with Down, Turner, or Williams syndrome, autoimmune diseases or selective IgA deficiency),
3. Tertiary: improved treatment and avoiding complications⁷

Marketing and media

The benefits of a GFD have been widely publicized, leading to a significant increase in food companies' production of gluten-free options, allowing CD patients to reproduce the dietary habits and patterns of the general population.²¹ To guarantee a GFD, the Food and Drug Administration (FDA) has endorsed a gluten-free labeling of a product as gluten content (<20 mg/Kg or 20 ppm) or declaring Free, Without, or No Gluten.

Drugs and reagents

The following reagents and drugs were used in the study: commercial ethanol (96%), ethyl alcohol PA (99.5%; Biotec^®), KOH (99% m/m; Vetec^®), HCl (36.5% v/v; Microquímica^®); Ferric chloride, gallic acid, KBr, 2,2-diphenyl-1-picrylhydrazyl (DPPH), Tween 80, flumazenil (Sandoz), granisetron hydrochloride (Kytril), dichloromethane, ethyl acetate, Folin-Ciocalteu, pizotifen maleate (Sandomigran^®), fluoxetine (Teuto), Cyproheptadine (Cobavital^®) and Diazepam (Teuto).

Botanical material

The A. indica bark was collected in the city of Tauá (040º18’05,4” W; 06º01’03,6” S) state of Ceará, Brazil, after obtaining authorization from SISBIO, according to the registration for the collection of botanicals, fungal and microbiological material, nº 29145-4. The botanical identification was carried out in the Prisco Bezerra Herbarium of the Federal University of Ceará, where an exsiccate was deposited under number 56044.

The primary nutritional approach in Pediatric Celiac Disease is a GFD. Difficulties in managing the Disease and all difficulties can lead to psychosocial distress and impaired Health-Related Quality of Life. Despite the essential role of diet, the risk of nutritional imbalances, metabolic syndrome, cardiovascular diseases, and obesity is higher in CD patients than in the average population. Nevertheless, strict adherence to the GFD is imperative. Therefore, managing CD requires a multidisciplinary team involving physicians, dietitians, and psychologists on a regular visit schedule. Lastly, it is vital to emphasize that caring for a pediatric patient with Celiac Disease must cover all aspects of the patient's life with a generous dose of empathy.

None.

Bibliographical Survey (NCM, JTD, GNH, TKW, MAC), drafting of the manuscript (TKW, NCM, MAC), critical manuscript revision (NCM, TKW, CDFJ).

None.

None.

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