The increasingly early recognition of celiac disease (CD) has resulted in an increase in the prevalence of the disease from 1:1000 (1) to 1:100 (2–4), which matches the figure forecasted by Magazzù et al (5) more than 12 years ago. Most doctors now recognize and diagnose CD in atypical cases and in apparently healthy individuals as well as in openly symptomatic subjects. Less is known about the outcome of patients once they have been diagnosed. Patients' adherence to a gluten-free diet ranges from extremely poor (6,7) to satisfactory (8–11). Long-term compliance with a gluten-free diet in CD is an increasing challenge given the impressive increase in diagnosis, but it will increase even more when self-managed diagnosis is available through the point-of-care test (12).
Children are mostly fed by parents. Consequently, good compliance in young children is related to familial awareness about the disease. However, problems arise in the case of teenagers. Children who have long accepted a gluten-free diet often rebel during adolescence, and a sizeable proportion will stop their gluten-free diet. Social integration, self-esteem, and school achievements are at risk in teenagers with CD and are likely to generate more problems than clinical complaints.
Quality of life is a major part of care. A study of self-rated quality of life in adults with CD did not reveal any major problems (13), but teenagers may well feel differently. In an attempt to shed light on this issue, we evaluated the global well-being (health, education, and social integration) of teenagers with CD with the aim of identifying predictors of good adherence to a gluten-free diet.
The objective of the study was to evaluate a cohort of teenagers with CD to identify risk as well as protective factors related to compliance with the gluten-free diet.
PATIENTS AND METHODS
Two hundred four patients (127 women and 77 men, sex ratio 1.65:1), from the Campania region (southern Italy) were consecutively admitted to this cross-sectional study on the basis of age between 13 and 30 years, CD diagnosed according to European Society for Pediatric Gastroenterology, Hepatology, and Nutrition revised criteria (14), and willingness to cooperate. Patients were divided into 2 groups: those diagnosed as children (younger than 13 years) and those diagnosed as teenagers (older than 13 years). Table 1 shows the baseline data of this cohort.
Each patient underwent a complete clinical check-up and 199 of them underwent a blood sampling. Tissue transglutaminase was assayed with an enzyme-linked immunosorbent assay.
An already standardized self-administered questionnaire modified by our previous study (13) was used throughout (Fig. 1). A psychologist working with our team adapted the form from internationally validated references (15–20).
The questionnaire was administered after a 2-day training session of the investigators (qualified S.E., O.E., R.D.M., M.E.C., C.N., and M.G.L.). We evaluated family and social integration, integration within the school environment, and sexual life, on visual analogue scales rated 0 to 25 ranging from poor to excellent. Social integration was investigated through the description of the daily life of the patients including number of outings, participation in social events, number of friends, and play activities. Feeling of self-constraint related to the gluten-free diet was also investigated. Smoking habit and school performance concluded the interview.
The second section, related to food habits, was managed by 2 dieticians (A.C. and M.L.). Patients were questioned about their diet in the previous day, using a standardized 1-day recall form, and about the total amount of gluten-containing foods ingested in the last 30 days, using a visual list of gluten-containing items available to this range of population. The daily gluten intake was estimated summing the total amount of gluten-containing foods ingested in the previous 30 days. The total protein intake was computed and gluten estimated by multiplying by a factor of 0.8 g of gluten per gram of vegetable protein (21).
Data were analyzed with the SPSS statistical package version 11 (SPSS Inc, Chicago, IL). Continuous variables were screened for normal distribution and transformed to reduce skewness, when required. Mann-Whitney and Kruskal-Wallis nonparametric tests were used to compare percentages in addition to the χ2 test. We used logistic regression analysis to estimate predictors of adherence to the gluten-free diet. Multivariate analysis was carried out with dietary compliance as dependent variable, and sex, age, familial interaction, school performance, school integration, and social integration as factors.
Symptoms at Diagnosis and Health Status
At diagnosis, 32 patients (15.7%) reported no health complaints; they were diagnosed by family screening. Of the remaining 172 patients, 112 (27.5%) reported recurrent diarrhea, 89 (21.8%) failure to thrive and/or pubertal delay, 41 (10%) weakness and/or anemia, 31 (7.6%) vomiting, 19 (4.7%) recurrent abdominal pain, 8 (2.0%) abdominal distensions, 8 (2.0%) headache or neurological disturbances, 7 skin disease (1.7%), 2 gastritis (0.5%), 2 (0.5%) constipation, and 2 (0.5%) hypertransaminasemia. Point prevalence (previous 30 days) of clinical complaints was evaluated by history taking (Table 2). Thirty-one of the 204 patients (15.2%) had at least 1 associated disease (Table 2). There was no major health complaint in the cohort. None of the girls had ever been pregnant.
Figures 2 and 3 show the distribution of height and weight in the whole group. Nineteen patients (9.3%) had height below the third percentile for sex and age and 25 (12.2%) had height between the third and the 10th percentile for sex and age. According to the growth standards we expected, among the 204 patients, 7 to be below the third percentile and 14 between the third and 10th percentile; there is a significant excess of short stature (Wilcoxon test P = 0.042) (22,23). As expected, weight was below the third percentile in 7 patients (3.4%) and between the third and the 10th percentile in 18 patients (8.8%). Weight was above the 75th percentile in 47 patients (23%). Weight excess (>97th percentile) was observed in 20 (9.8%) patients. Height and weight percentiles were not related to age at diagnosis or to the interval from first symptoms to diagnosis.
After grouping the patients by age, we analyzed the number that passed the school level expected for their age. We compared these data with the regional statistics of school performance: 13% of our patients stopped at the primary or secondary level against 53% of the regional reference, 16% at high school against 24.4%, and 3% at university level against 10.8% of the regional reference (24) (χ2 = 5.33, P = 0.07) showed no difference.
Self-rated Social Integration
A total of 181 (88.7%) patients reported good family integration, 186 (91.2%) reported good social relationships, and 180 reported (88.2%) good school integrations. On the contrary, 110 (53.9%) felt that CD occasionally or often limited their social life.
One hundred fifty (73.5%) patients declared they adhered completely to a gluten-free regimen. Fifty-four (26.5%) reported occasional (less than or equal to 2/month) or frequent (>2/month) lapses from the diet. There was no difference in compliance between males and females or among age groups. Dietary compliance did not affect current weight and height. The interview dietary enquiry revealed that 29 of the 54 (53.7%) poor compliers had assumed a quantity of gluten from 0.001 to 1 g/day, 14 of them (25.9%) from 1 to 5 g/day, and 11 (20.4%) >5 g/day during the last month. Types of food eaten in transgressions are pizza in 15 of 54 (27.8%), snacks or/and sweets in 11 of 54 (20.4%), bread in 10 of 54 (18.5%), and 18 of 54 (33.3%) ate several gluten-containing foods.
Compliance With a Gluten-free Diet and Serology
Not all “poor compliers” were identified by a serum anti-tissue transglutaminase antibodies (tTG) assay, and a large proportion of bad compliers tested had negative tTG (Table 3). Among patients with high gluten intake (>5 g/day) 7 of 11 (63.6%) had negative tTG and 4 of 11 (36.4%) had positive tTG. Among patients with little (0.001–1 g/day) and medium (1.001–5 g/day) gluten intake, we found 24 of 28 (85.7%) and 9 of 14 (64.2%) with negative tTG, whereas 4 of 28 (14.3%) and 5 of 14 (35.7%) had positive tTG, respectively (χ2 = 54.663, P = 0.000). As shown in Figure 4, the amount of gluten ingested daily was significantly related to the percentage of patients with increased tTG serum levels (χ2 = 38.872, P = 0.000, r = 0.391); in the lower part of the figure individual tTG titers are shown for the 2 groups.
Compliance With a Gluten-free Diet and Health
One hundred eleven of the 150 patients who declared good compliance (74%) and 31 of the 54 poor compliers (57.4%) had no health complaints. Conversely, health complaints were more frequent among bad compliers (23 of 54) than among good compliers (39 of 150) (χ2 = 6.025, P = 0.014). Table 4 shows the symptoms we identified in these 2 groups of patients and their correlation with daily gluten intake. As shown, the percentage of patients with symptoms was significantly related to the amount of ingested gluten daily (χ2 = 9.117, P = 0.028).
Serology and Health
Among 182 patients with negative tTG, 127 (70%) had no health complaints, whereas 55 (30%) reported several symptoms: 18 (9.8%) had recurrent abdominal pain, 9 (4.9%) had diarrhea, 9 (4.9%) had constipation, 9 (4.9%) had headache or neurological disturbances, 5 (2.7%) had failure to thrive, and 5 (2.7%) had skin diseases. Of the remaining 17 patients having positive tTG, 10 (58.8%) were asymptomatic, whereas 7 (41.2%) had health complaints: 3 had (17.6%) recurrent abdominal pain, 2 had (11.7%) failure to thrive, 1 had (5.8%) constipation, and 1 had (5.8%) skin diseases. There is no statistical correlation between tTG and symptoms (χ2 = 19.824, P = 0.707).
Compliance With a Gluten-free Diet and Social Integration
Table 5 shows the relation between compliance with a gluten-free diet and social integration. Family integration did not affect compliance, and similarly, there was no difference in compliance between patients with good school performance and those with sufficient to average performance. However, people with excellent school integration adhered to the diet better than those with bad or sufficient school integration. About half of the patients with poor school integration did not adhere to the diet. A good social relationship was significantly related to dietary compliance. People without feelings of self-constraint complied better with the diet than those with occasional or persistent feelings of self-constraint. There were no differences among sex or age groups.
Nonsmokers had significantly better dietary compliance than smokers in the age group 19 to 26 years, whereas there were no differences in the other age groups (Table 6).
Similarly, psychosexual relationships were unrelated to adherence to the diet (Table 5). Twenty-four of 144 patients (16.7%) with a stable partner did not tell their partner they suffered from CD.
All of the variables that concern family, school, and social interaction are related. Therefore, these cannot be individually used as independent predictors of a good or poor compliance with the diet. To select the best predictors, we carried out a multivariate analysis with dietary compliance as dependent variable, and sex, age, familial interaction, school performance, school integration, and social integration as predictors. Only school integration significantly contributed to the likelihood of good or poor compliance (Wald statistics = 10.83, P < 0.001, odds ratio 0.44). For each degree of improved school integration, we have about 56% less transgression from the gluten-free diet. None of the other variables contributed significantly (>10%) to the increase in the log likelihood.
For many years, physicians have focused on the diagnosis and molecular and cellular markers of CD, with scarce attention being given to the care and well-being of the patient. Indeed, the ratio of articles devoted to CD diagnosis versus those dealing with the care of patients is >10:1. By a PubMed search (key word “celiac disease”), we found only 28 articles (9%) analyzing the patients' treatment and 227 (75%) focused on the diagnosis on a random sample of 300 articles published in the last 3 years.
Whereas young children with CD usually adhere to a gluten-free diet because of parental influence, the situation is more complex in adolescents with CD. Indeed, they frequently reject parental advice; school and social environments are their daily scenario; they are exposed to the comments of their peers, and not infrequently they choose to restrict social relations to easy ones. Many factors contribute to the self-perceived restriction on the social life of these youngsters. The first is the limited awareness of the “celiac condition” within our communities, the second (sometimes crucially important) is the excessive tone of dietary prescriptions given by doctors, dieticians, and patients' groups. The patient can become obsessed with the fear of traces of gluten in canteens and restaurants or in common foods and snacks that are not made with gluten-containing flours. Most patients are not aware that “100 parts per million” means 100 mg of gluten protein per million milligrams (1 kg) and thus 10 mg/100 g of flour, a trace amount that has never been shown to be toxic (25–27).
Compliance with a gluten-free diet among adolescents has traditionally been reported poor in several studies. Kumar et al (6) reported that up to 44% do not comply with the diet. Many of these youngsters had a gluten-free diet at home, but were consuming gluten-containing foods in social meals. Teenagers go out for pizza or sandwiches frequently; they use pizza as a snack also at school. Similarly, it has been widely accepted that a significant proportion of adult patients do not adhere to a gluten-free diet (28). Compliance with a gluten-free diet in Campania is regarded by the patients and the family as a major deprivation from food in general, which is understood as pasta and bread. In a different scenario, a “happy celiac world” has been reported recently by Roos et al (29,30) suggesting that different medical management may eventually lead to different “care” of the patient. This is one of the major reasons for this study and our special care toward adolescents. Since 1979, we have provided, through the National Health Service, a complete supply (valuable at €200/month), of gluten-free pasta, pizza, and snacks. In Campania the Celiac Society set up in 1999 a factory of freshly baked gluten-free products that is free to patients.
In our study, 53 of 204 (26%) teenagers with CD had occasional transgressions to the diet, but only 1 of 4 of them had positive tTG (Table 3). Our group as well as other groups have analyzed the relation between serology and compliance to the diet, since the time when only anti-gliadin antibodies were available (31). Unfortunately, anti-transglutaminase antibodies are related to mucosal damage (32) and this may come late after prolonged dietary transgression, so sensitivity in patients with moderate transgression is low (33). We are indeed been impressed by the relation, shown in Figure 4, between amount of gluten ingested and tTG. We did not expect to find such a significant relation, because the vast majority of our patients do substantially adhere to a gluten-free diet.
As shown, in this study there is no strict relation between gluten ingestion and actual health status with symptoms: 39 of 150 compliers do experience minor symptoms as bad compliers do. We have no straight explanation, but point prevalence of any cohort of individuals will produce a list of symptoms of the kind shown in Table 4.
According to Ciacci et al (34), even a short period of gluten-free diet in childhood may produce a significant difference in the health status and performance of adult patients. Indeed, our cohort is not free from problems: 31 (15.2%) suffer from an associated disease.
Growth in our cohort was not ideal compared with the national standards: height was below the third percentile in 19 (9.3%) patients (7 expected). In other studies excess weight and obesity has been described in newly diagnosed patients as well as in patients after 2 years of gluten-free diet (35).
The self-perceived quality of life is acceptable in Italian patients with CD (13): our cohort of adolescent patients did not report any major problems in their social life or with their families. However, the relatively small proportion of patients with school, familial, or social problems adhere less to the gluten-free diet. School achievements were not related to the diet, but integration in the school environment was. Less integration into the school domain, meant less adherence to the gluten-free diet. Similarly, feelings of self-constraint and poor social integration were both related (cause or effect) to dietary compliance. Multivariate analysis confirmed that the main predictor of compliance with a gluten-free diet is the quality of integration of the patient in the school environment, regardless of the educational achievements. There is obviously a circular relation between better school integration and compliance with the gluten-free diet. The capacity to cope with the gluten-free diet and the school relationship is indeed conditional to the personality and cultural background of the individual. As a consequence we should work toward the individual's personality, which is unfortunately far from our specific task: children who do not receive from their home and school environments enough support should be paid more attention by us, the care team, and the school health system. We have to identify a red flag, which can be used to support the “weak” ones.
It is remarkable that smokers comply less than nonsmokers, perhaps because they are more inclined to transgressions and they are not too concerned about their health status.
Diagnosis of CD is a lifesaving or, more frequently, a health-improving action. But the next step is to focus on the care of patients; most of them will cope satisfactorily with a gluten-free diet, but others will not. Our data suggest that patients who feel limited in their social expression, especially those with poor school integration, tend to be noncompliers. Perhaps one may envisage caregivers (doctors included) setting up a bridge of communication with the school environment with the aim of promoting a reasonable integration of the adolescent affected by CD into the educational domain. Patient tailored intervention is likely to help those most likely to fail to comply with a gluten-free diet.
We thank the patients and their families. We are grateful to Jean Ann Gilder for editing the text.
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