Introduction

Celiac disease (CD) is a chronic immune-mediated disease triggered by gluten intake in genetically sus ceptible patients^1,2. Although there is no cure, it has highly effective treatment through the gluten-free diet (GFD), which should be strict and on a permanent basis¹. However, keeping this diet implies difficulties for the patient and modifies his/her daily life, for ins tance, the patient has to modify his/her eating habits, to adapt his/her cultural preferences to the availability in the market, be able to ensure his/her access to safe gluten-free foods on which the information is often insufficient and also are very expensive. Failure to ade quately follow the GFD exposes the patient to medi cal complications, increases morbidity and mortali ty, and may deteriorate the patient’s quality of life^3,4. Although there are initiatives that actively seek other non-dietary therapies^5,6, to date, this diet is the only available treatment and requires that an important as pect of long-term management focus on supervision and promotion of diet adherence^7,8. Blood antibodies measurement (anti-transglutaminase 2 {tTG}, anti- endomysium or anti-deamidated gliadin peptides) has high sensitivity and specificity to make diagnosis in both children and adults, however, evidence obtai ned in several studies show controversial results about its role in the follow-up of CD, for example, the evo lution of the histological lesion is not consistent with serologic results^9-11. When comparing tTG results with in-depth interviews by a nutritionist trained in CD, a study in the United States showed that 30% of the interviewed patients who did not adhere to the diet had negative tTG¹². In the Netherlands, another study showed that 40% of dietary non-compliances may go unnoticed when patients are assessed by serology or by Biagi questionnaire¹³. In our experience, 22% of pa tients who were classified as adherents in an in-depth interview had positive tTG and 22% of those who clas sified as non-adherents had negative tTG (submitted for publication, in review 2019). Hence, some authors currently propose that an in-depth interview by a trai ned professional would be a necessary and comple mentary way to follow-up the patient, allowing address qualitative as well as quantitative aspects^14,15. This de mands information about the changes that following the GFD implies in daily life^7,14 and its repercussions on the patient’s quality of life. In our country, there is no information on these subjects and, additionally, they are strongly influenced by local culture, which makes data obtained in other societies not easily applicable to ours.

Health-related quality of life (HRQoL) is a com plex and multidimensional concept that, in general terms, refers to the impact of health and disease and/or their treatments on the individual’s quality of life from the perspective of the patient^16-18. There are three HRQoL measurement questionnaires that can be used on children and adolescents. Two are specific for ce liac disease, the TACQOLCD^19-21 and the Celiac Disea se Dutch Questionnaire CDDUX²². The TACQOLCD is a questionnaire in which the ‘welfare state’ of chil dren has been estimated by researchers and physicians (‘top-down’ methodology), thus it does not provide information from the point of view of children or their parents. It is limited by the fact that it only contains questions related to symptomatology. The CDDUX, developed in the Netherlands, is a bottom-up instru ment, in other words, the baseline information for constructing the questions was obtained from the chil dren and their families. Therefore, this questionnaire is considered as ‘child-centered’ and is designed for children and their parents/caregivers to generate, prio ritize, and explain the issues that interest them, thus obtaining data that may even have previously gone un noticed. As a methodology, it is not aimed at qualifying the state of health or adherence to the gluten-free diet, but to assess the patient’s perception of their welfare level. The design is based directly on the generic questionnaire DUX 25 which evaluates HRQoL²². Given how difficult it is to evaluate these aspects, the scarce information in children and, especially in Chile, about HRQoL and CD, the objectives of this work were: i) to measure HRQoL in Chilean celiac patients treated in Santiago (capital city), ii) to determine the concordan ce between patients and caregivers, and iii) to compare the results with those reported in the international li terature.

Patients and Method

The HRQoL (Health-Related Quality of Life) measurement instrument

This questionnaire, specific to CD, was transla ted, adapted, and validated in Argentina and includes two versions, one for children and another one for parents/caregivers^22,23. The instrument measures the quality of life through the identification of different emotions expressed in five facial expressions, conside ring that the visualization of facial expression is more identifiable with a certain feeling, which could be long and difficult to define globally in words (Tables 1 and Table 2). It gathers information in three areas, summarized in the following three subscales: i) having CD (how the child feels when offered gluten-containing food or when he/she thinks of gluten-containing food, questions 1, 2, and 10), ii) communicating with others (how the child feels when talking about celiac disease with others and/or explaining it to others, questions 3, 6, and 7), and iii) the diet (how the child feels about diet adherence and restrictions, and all aspects of his/ her life, questions 4, 5, 8, 9, 11, and 12). In the case of the caregiver, the questions are interpreted as the caregiver’s appreciation of how the child feels in each of the addressed situations. For children/adolescents and for parents/caregivers, the self-administered version was used. The 5 options of facial expressions are interpreted as very bad, bad, neutral, good, and very good. The person must mark the one that best repre sents his or her feelings facing the situation posed by the question. The instrument addresses 12 items grou ped into the three subscales (6), each ‘face’ assigns 1 to 5 points, from the saddest (1 point) to the happiest (5 points) (five-point Liker scale), and the sum of the answers gives a final score, on a scale of 1 to 100. The higher scores indicate better quality of life (1 to 20: very bad, 21 to 40: bad, 41 to 60: neutral, 61 to 80: good, 81 to 100: very good).

Table 1 CDDUX questionnaire applied to patients. 

Table 2 CDDUX questionnaire applied to caregivers. 

Results

74 individuals were evaluated, corresponding to 37 caregiver-child dyads. (Table 3) shows the socio-demo graphic characteristics. 40.5% of participants present a GFD adherence for more than 5 years, and regarding how they follow the diet, 59.5% declared that they fo llowed it strictly. In 94.6% of the cases, the school staff was aware of the child’s diagnosis, however, according to the caregiver’s appreciation, only 35.1% know about celiac disease and the requirements of its treatment. More than 50% of patients and their caregivers report good/very-good on the subscales ‘having the disease’ and ‘maintaining the gluten-free diet’ but not on ‘com munication’, which showed the highest percentages of bad/very bad responses. (Figure 1) shows the distribution of patient and caregiver answers in the three evaluated areas. No significant differences were found between patients and caregivers. When expressing the answers in extreme groups (bad/very bad, neutral, and good/ very good), the comparison between children and their caregivers showed significant differences in the subsca le GFD, with a higher percentage of bad/very bad score in patients (24.3%) than in caregivers (17.1%). Out of the 12 patients who self-reported as bad and very bad, 8 were classified differently by caregivers, 4 as neutral, and 4 as good or very good (% concordance=35.14%, p = 0.0426).

Table 3 General characteristics of 37 dyads evaluated for health quality of life in celiac disease. 

Figure 1 Patients and caregivers' responses in the categories "having cD", communication with others, and the gluten-free diet, expressed as percentages of responses classified as very well, well, neutral, bad and very bad. 

Quality of life

There were no significant differences between the HRQoL perceived by patients and their caregivers, both in the overall score and by subscale (Table 4). When analyzing patient answers, the variables sex, age (older or younger than 11 years), region of residence (MR vs. other), GFD duration (more or less than 5 years), decla ration of strict GFD adherence (strict vs. not strict), the re were no significant differences in the overall score of HRQoL or in the subscales. In caregiver responses, the overall HRQoL score was better in male patients (73.4 v/s 61.5, p = 0.022) and in those who followed GFD non- strictly (73.9 v/s 63.3, p = 0.049). On the GFD subscale, scores were higher for males (77.0 v/s 64.4, p = 0.04) and for those older than 11 years (76.5 v/s 63.5, p = 0.035).

Table 4 Scores obtained by celiac patients in different countries, assessed by Celiac Disease Dutch Questionnaire (CDDUX). 

Discussion

The results show that more than 50% of patients and their caregivers report that they are good/very good on the subscales ‘having the disease’ and having to ‘maintain the gluten-free diet’, suggesting that they have learned to manage both the fact of having (or being) a chronic patient in the family and the need to maintain a restrictive diet as a treatment. In contrast, the highest percentages of bad/very bad responses are on the subscale ‘communication’, showing that the dyad finds it difficult to maintain communication with others. In this subscale, the high percentage of neu tral responses is striking, which, in the area of coping with chronic diseases, is interpreted as indifference. It is well known that chronic diseases affect the HRQoL, which is difficult to measure because in the evaluation influences the daily experience of eating and relating with others, which varies over time²⁴. If the experien ce is positive, the emotion that appears is of welfare, while if it is negative, it is associated with discomfort. Neutral answers may reflect uncertainty about gluten free eating when you are with others, and the emotions that appear will depend on past experiences. Studies in other countries^22,23,25-27 (Table 4) show that, contrary to what we found, the subscale that has the best score is communication. We could interpret these findings as saying that in our country there are health care actions that allow having a basic knowledge of the disease and its treatment (GFD), however, they are insufficient in the communication area. The information generated by the National Socioeconomic Characterization Sur vey (CASEN) supports this. According to 2015 data, only 0.3% of the population participates in self-help groups in health²⁸. In the networks and social connec tion dimension, the indicator of social support and participation is 6.1% at the national level out of 7.1% in the metropolitan region, which reflects the low le vel of social interaction of the Chilean population²⁹. In quality of life and social support studies, quality of life scores were higher for those that only used ‘face-to- face’ social support compared with ‘online assistance’ (72.6 vs 66.7; p < 0.0001). Longer duration of face-to- face social support use was associated with a higher quality of life scores (p < 0.0005)³⁰.

Cultural factors (micro-social level) and public policies (macro-social level) influence the results obtained in different countries. In the total valuation of the questionnaire, the Chilean values are the highest among the 6 countries analyzed and compared with those reported in Argentina (66.1 and 64.9, respecti vely) (Table 4). However, the concordance between pa tients and caregivers was lower in our study (39.2%) compared with what was reported in Argentina (64%)³¹. Interestingly, caregivers’ responses showed significant differences when analyzed by sex, where the overall CDDUX score reflects their perception that males have better HRQoL. In the Quality of Life and Health Survey (ENCAVI 2016)³² in populations over 15 years of age, 63.8% of women reported having a good/very good quality of life compared with 71.1% of men. This self-perception referring to quality of life, in general, could be transferred to the caregivers’ opi nion of this study (61.5% women) regarding the pa tients’ HRQoL. The caregiver score was also higher in the group of children over 11 years of age. It may be interpreted as that the older child has better capacities to become aware and decide on his or her self-care, and this could be perceived by the caregiver as his or her HRQoL is better.

When asking directly if the patient is dieting, 78.6% of caregivers say they are. It is remarkable, then, that 21.4% of caregivers recognize that GFD is not followed properly, while it represents the treatment of the disea se and must be strict and for life. The school role deser ves a special comment. The results show that, although schools know the diagnosis of the child (94.6%), 35.1% are not clear on how to support the patient and his/ her family in the treatment with GFD, which makes it difficult for the school to act as the institution that pro vides assistance and social support to the celiac patient, who as a chronic patient requires long-term support. This point is relevant considering the long school day (8 hours per day) of our country. Initiatives such as the ‘celiac PAE’ (National feeding program for vulnerable school age children) approach the problem from the material side, offering safe gluten-free foods. There are several studies that show that society’s general ignoran ce of what it means to have CD is another important barrier to dietary compliance. They agree on the im portance of promoting and supporting social support strategies based on a comprehensive understanding of the estrangement and marginalization experiences that celiac patients experience in their social relationships through food^33-35.

In summary, the results show that the HRQoL of the evaluated celiac children appears as one of the best reported in our region. The low concordance detec ted, especially in communication, indicates that the caregivers’ perception is not a proxy of the patients’ opinion, and this is relevant since they are the ones who usually give the information during follow-up visits of celiac children. These findings emphasize the need to establish a model of comprehensive care that includes the family and the school, in order to impro ve understanding, support, communication and, the refore, the HRQoL of children and adolescents with celiac disease.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed ac cording to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regu lations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.