| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ORIGINAL ARTICLES |
From the Department Internal Medicine I (W.H.), Klinikum Saarbrücken, Saarbrücken, Germany; Department of Internal Medicine V (F.M.), Kliniken Essen-Mitte, Knappschaftskrankenhaus, Essen, Germany; Department of Internal Medicine I (W.F.C., J.S.), Johann Wolfgang von Goethe-Universität Frankfurt, Frankfurt, Germany; Department of Internal Medicine I (A.S.), Friedrich-Schiller Universität Jena, Germany.
Address correspondence and reprint requests to Winfried Häuser, Department of Internal Medicine I, Klinikum Saarbrücken gGmbH, Winterberg 1, D-66119 Saarbruecken, Germany. E-mail: whaeuser{at}klinikum-saarbruecken.de
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
Methods: A total of 1000 adult patients with CD from the German Celiac Society completed a medical (including bowel) and a sociodemographic questionnaire, the Short Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale through a postal survey.
Results: Of 412 respondents with reported biopsy-proven diagnosis with major adherence to a gluten-free diet (GFD) for 
1 year, 96 (23.3%) patients fulfilled the modified Rome I criteria for IBS. Of these 96 patients, 76 (79.2%) sought help (medical and/or nonmedical) due to bowel symptoms (referred to as patients with IBS). IBS-type symptoms had a significant negative impact on the physical summary score of the SF-36 (p = .05). Mental disorder (OR = 2.29; ß = 0.83; p = .006); female sex (OR = 2.34; ß = 0.85; p = .03), and occasional nonadherence to GFD (OR = 1.74; ß = 0.56; p = .05) were risk factors for IBS-type symptoms. Active medical comorbidities predicted IBS-patient status (OR = 0.40; ß = –0.92; p = .001).
Conclusions: The data support the biopsychosocial model of IBS: IBS-type symptoms in adult patients with CD can be explained through an interaction of clinical and sociopsychological mechanisms.
Key Words: celiac disease • irritable bowel syndrome • biopsychosocial model
Abbreviations: CD = celiac disease; FGID = functional gastrointestinal disorder; GFD = gluten-free diet; HRQOL = health-related quality of life; IBD = inflammatory bowel disease; IBS = irritable bowel syndrome.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
CD can be defined as an inflammatory disease of the small intestine characterized by a persistent intolerance to gluten proteins contained in wheat, barley, and rye. Serologic screening studies demonstrated a prevalence of CD between 1:125 and 500 in the general American and European populations. Symptoms of classical CD are abdominal pain, diarrhea, and weight loss. By removing gluten from the diet—which requires a major change in diet with a complete avoidance of wheat-based foods, such as sandwiches, pasta, pizza, pancakes, or cookies, which constitute a major part of nutrition in western countries—full histologic and serologic remission can be attained. Histologic recovery on a gluten-free diet (GFD) can take up to 1 year (7). However, whether strict GFD and histologic remission are accompanied by full clinical remission together with a health-related quality of life (HRQOL) comparable with those of healthy control subjects or the general population is still under debate. Mustalahti et al. demonstrated that Finish patients with symptom-detected CD who started a GFD showed a rapid reduction of gastrointestinal symptoms and improvement in subjective well-being (8). In contrast, Midhagen and Hallert reported more gastrointestinal symptoms, measured by the Gastrointestinal Symptom Rating Scale, in Swedish patients proved to be in histologic remission after 8 to 12 years of GFD compared with the general population sample (9). Persistent gastrointestinal symptoms in patients with CD, who observe a GFD, can be labeled as "irritable bowel type." In a study on Northern Irish patients with CD, O’Leary et al. (6) demonstrated that most of them, reportedly adhering strictly to a GFD, showed a 20% prevalence for meeting the modified Rome I criteria of IBS (10). The HRQOL of patients with CD and with IBS, measured by the Short Form Health Survey (SF-36), was markedly lower than for those without symptoms. Female gender and short duration of CD were associated with IBS-type symptoms, whereas nonadherence to diet and age at the time of the CD diagnosis or during the study were not significantly associated with positive Rome I criteria. The authors concluded that mucosal inflammation in CD may dispose to IBS-type symptoms (6).
The few studies on persistent gastrointestinal symptoms in patients with CD on a GFD and their determinants used univariate statistical analysis in clinical samples at the secondary or tertiary care level and did not assess the potential influence of non-CD-specific factors, which are considered to be a risk factor of IBS, such as mental disorders (11). No study differentiated between patients with CD and with IBS-type symptoms seeking medical help or not. The aims of our study therefore were: a) to assess the frequency of IBS-type symptoms and related healthcare-seeking behavior and their impact on HRQOL in a representative German nonclinical sample of patients with CD; and b) to determine the potential predictors of IBS-type symptoms and healthcare-seeking behavior using a multivariate approach. We hypothesized that IBS-type symptoms in patients with CD are determined by CD-specific clinical factors (duration of and adherence to GFD; latency of CD diagnosis) (6) as well as by non-CD-specific psychosocial factors such as female gender and mental disorder (6,11). Furthermore, we expected that healthcare use due to gastrointestinal symptoms in patients with CD is best predicted by non-CD-specific factors such as mental disorder, female gender, educational level (11,12), and medical comorbidities (13).
|
PATIENTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
The normative data of SF-36 were obtained from a survey on 2443 persons (55.6% women; mean age 47.7 years, standard deviation (SD) = 17.2), representative of the general German population (14).
Questionnaires
The medical questionnaire asked for the history of CD diagnosis, compliance with GFD and CD-associated diseases. The medical questionnaire had been developed by four gastroenterologists with expertise in CD. Most questions were derived from the medical questionnaires in other celiac health surveys (15,16). IBS-like symptoms, according to the modified Rome I criteria (10), were assessed by a German version of a bowel questionnaire developed by Neal and colleagues (17) for postal surveys. The German version was based on a forward and backward translation of the questionnaire. Symptoms were defined as IBS-type if the patients reported abdominal pain relieved by defecation or associated with 3 of the following symptoms: a) altered stool frequency or stool form (hard, loose); b) stool passage (straining, urgency, sense of incomplete evacuation); c) mucus per rectum; and d) bloating or feeling of abdominal distention for at least 2 days/week or at least 3 months/year in the bowel questionnaire (17).
Questions regarding healthcare-seeking behavior were derived from the questionnaire of the German population-based study of Icks et al. investigating the prevalence of functional bowel disorders (18). A comorbidity list within the medical questionnaire—regarding current medical comorbidity (diseases of the cardiovascular, respiratory, nervous, endocrine, urogenital, musculoskeletal, and gastrointestinal system not associated with celiac disease)—was confirmed through the information on current medications (drugs taken because of the categories of comorbid). Comorbid diseases (without IBS and CD-associated diseases) with current pharmacological treatment were defined as "active medical comorbidities" (19). A "social class index" was derived from the data on education, occupational status, and available income. For this index, data of a representative sample of the general German population were used (20). The two comprehensive indices (physical component summary and mental component summary) from the German version of the Medical Outcome Study SF-36 were used for the measurement of HRQOL (14,21). The two subscales, anxiety and depression, of the German version of the Hospital Anxiety and Depression Scale (HADS) were selected for assessing anxiety and depressiveness. Respondents who scored 11 on either subscale showed a symptom severity of depression or anxiety indicative of a probable mental disorder (i.e., clinical depression or anxiety disorder) (22,23).
Statistical Analysis
Descriptive data and univariate analysis were analyzed using Winstat for Excel (Version 2001.1, R. Fitch Software, Germany). Regression analyses were carried out using the Statistical Package for Social Sciences for Windows (SPSS Version 13.0, Chicago, Illinois). Up to 25% of the missing items of the HADS-D and SF-36 were replaced by the median of the items of the respective subscale. If >25% of the items of a subscale were unanswered, the questionnaire for this person was excluded from further analyses. Data derived from descriptive statistical analysis are presented as percentages for categorical variables and as mean ± SD values for continuous variables. Comparisons of proportions within the study sample were performed by 
2 test and, because most continuous variables were not normally distributed, with nonparametric procedures. Although only the mean and SD values of the SF-36 scores of the representative German population sample were available, the comparisons with this sample were calculated by the Student’s t test. Significance level was set at a two-sided p 
.05.
Because we were interested in assessing the possible impact of IBS-type symptoms compared with sociodemographic and CD-specific factors as well as other comorbidities on the HRQOL, the summary scores of the SF-36 served as dependent variables for the multiple regression analysis. Present age, gender, social class index, latency of diagnosis, duration of GFD, reported adherence to GFD, number of CD-associated diseases, active medical comorbidities, and probable mental disorder measured by the HADS and IBS-type symptoms were thus included as independent variables in a direct multiple regression analysis.
To estimate the possible relative risk for IBS-type symptoms and IBS-type symptoms related to healthcare-seeking behavior due to sociodemographic variables, CD-associated variables and other comorbidities, a logistic regression was performed. The logistic regression method is explained as follows: inclusion = all independent variables included within a single step; no automated stepwise selection procedures were used. Based on our hypotheses derived from the literature, reported latency between first symptoms and final CD diagnosis, reported duration of GFD, reported adherence to GFD, gender, and probable mental disorder measured by the HADS were tested as predictors of IBS-type symptoms. Gender, probable mental disorder measured by the HADS, number of CD-associated diseases, active medical comorbidities, and social class index were tested as predictors of IBS-associated healthcare-seeking behavior. The internal validity of the model was tested by the Hosmer-Lemeshow test and by shrunken r2 statistic.
Ethics
The study was approved by the regional board of physicians of Saarland. Data protection requirements were observed throughout the study.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
18 years). Although six questionnaires were excluded due to missing data, a total of 516 questionnaires were usable for further analyses. Of these, 213 (41.3%) respondents indicated that the CD diagnosis was made by duodenal biopsy, 37 (7.2%) by serologic tests (CD-specific antibodies), 34 (6.6%) by stool tests (transglutaminase antibodies), and 232 (45.0%) by duodenal biopsy and serologic tests. In total, 446 patients reported a biopsy-proven CD. Of these 446 patients, 18 were excluded because the reported adherence to a GFD lasted <1 year. Sixteen patients were excluded because they reported a major nonadherence to GFD. Thus, the analysis was limited to 412 patients self-reporting a biopsy-proven CD, on a GFD of 1 year with major adherence to the regimen.
Comparison of Celiac IBS-Type Patients With Non-IBS-Type Patients
The modified Rome I criteria of IBS (10) were met by 96 of 412 (23.3%) of the patients. Some sociodemographic and medical data of the patients with CD with and without IBS-type symptoms are presented in Table 1.
|
IBS-like symptoms were associated with a longer interval between the first symptoms and CD diagnosis, a lower frequency of CD-associated diseases and active medical comorbidities, and a higher frequency of a probable mental disorder (HADS) compared with patients with CD and without IBS-type symptoms (all p < .05). Moreover, more women than men reported IBS-like symptoms. Therefore, the group of patients with IBS-like symptoms included more females. There were no significant differences with regard to current age, marital status, social class index, and adherence to GFD. IBS-type patients reported a higher frequency of medical consultations (57.3% versus 15.1%; 2 = 70.0; p < .001), drug prescriptions (40.2% versus 11.6%; 2 = 40.0; p < .001), over-the-counter medication (34.0% versus 11.9%; 2 = 26.1; p < .001), alternative health care (25.7% versus 8.9%; 2 = 18.5; p = .02), and psychotherapy (15.4% versus 3.9%; 2 = 18.7; p < .001) compared with patients without IBS-type symptoms.
Because 76 of 96 (79.2%) of the patients with CD sought medical help regarding their bowel symptoms (at least one of the following: medical consultation, prescribed drugs, over-the-counter drugs, acupuncture, homeopathy, psychotherapy), they could be labeled as IBS patients. These "IBS patients" differed from "nonconsulting irritable bowel-type celiac patients" only in that they had a higher frequency of active medical comorbidities (2 = 21.1; p < .001). Of these patients, 25 of 76 (32.9%) could be described as high users (at least two of the following: prescribed drugs, over-the-counter drugs, acupuncture, homeopathy, and psychotherapy).
Impact of IBS-Type Symptoms on HRQOL
Whereas patients with CD and without IBS did not differ from the normative German population sample in the physical and mental summary score of the SF-36, patients with IBS-type symptoms scored lower in the physical summary (z = –6.7) and the mental summary score (z = –4.2) than patients without IBS-type symptoms (both p < .001) (Figure 1).
|
The results of the multiple regression analysis to assess the relative impact of IBS-type symptoms compared with other comorbidities, sociodemographic, and CD-specific factors on HRQOL are presented in Table 2. The variables were coded as follows: a) present age (years-continuous); b) gender (1 = female; 2 = male); c) social class index (1 = lower class; 2 = middle class; 3 = upper class); d) latency of diagnosis (years-continuous); e) duration of GFD (years-continuous); f) reported adherence to GFD (1 = most of the time; 2 = all of the time); g) number of CD-associated diseases (0,1,2, ...); h) active medical comorbidities (omitting IBS and CD-associated diseases) (0,1, ...); i) probable mental disorder measured by the HADS (1 = yes; 2 = no); and j) IBS-type-symptoms (1 = yes; 2 = no).
|
IBS-type symptoms had a significant independent negative impact on the physical summary score (p = .05) of the SF-36. Older age and number of active medical and CD-associated comorbidities were the strongest predictors of a reduced physical summary score. Compared with these determinants, the predictive value of IBS-type symptoms was small. Mental disorder and a number of active medical and CD-associated diseases were the strongest predictors of a reduced mental summary score. IBS-type symptoms had no significant impact on the mental summary score of the SF-36. Remarkably, CD-specific clinical factors had no significant impact on the HRQOL.
Risk Factors of IBS-Type Symptoms and Associated Healthcare Seeking
The results of the logistic regression analysis to identify predictors of IBS-type symptoms and associated healthcare-seeking behavior are presented in Table 3. The variables were coded as follows: a) IBS-type symptoms (1 = yes; 2 = no); b) IBS-type symptoms related to healthcare-seeking behavior (1 = yes, 2 = no); c) reported latency between first symptoms and final CD diagnosis (years-continuous variable); d) reported duration of GFD (years-continuous variable); e) reported adherence to GFD (1 = most of the time; 2 = all of the time); f) gender (1 = female; 2 = male); g) probable mental disorder (1 = yes; 2 = no) measured by the HADS; h) number of CD-associated diseases (0,1,2, ...); i) active medical comorbidities (without IBS and CD-associated diseases) (0,1, ...); and j) social class index (1 = lower class; 2 = middle class; 3 = upper class).
|
Mental disorder, female gender, and occasional nonadherence to GFD led to a 77.4% probability of IBS-type symptoms. Active medical comorbidities led to a 77.4% probability of classification to IBS-patient status. The models generated by the logistic regression were significant. The levels of significance in the Homser-Lemeshow test were above the predefined p = .05, thus confirming the adequacy of the models (Table 4).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
Our sociodemographic and medical data on German patients with CD are comparable with the results of American and other European studies. The return rate, gender ratio, present age, age at diagnosis, reported adherence to GFD, and frequency of CD-associated diseases in the German sample were all comparable with those in the samples of American (15), Canadian (16), and Italian (24) celiac health surveys. The prevalence of IBS-type symptoms in German patients with CD was higher than the one determined in the general German population, for which Icks et al. reported an IBS prevalence of 12.1%, according to the Rome I criteria, despite the lower frequency of symptoms required for the diagnosis of IBS in the German IBS study (at least six times a year) compared with our study (at least 3 months a year) (18). However, the frequency of 23% for the IBS diagnosis, according to the Rome I criteria in our sample, did not differ significantly from the 20% in the study of O’Leary and colleagues in 150 Northern Irish patients, where most of the patients reportedly adhered to a GFD (6). Interestingly, there is a documented 26% frequency of IBS-type symptoms (according to the Rome II criteria) in silent Crohn’s disease (5).
In our German sample, we confirmed the negative impact of ongoing gastrointestinal (IBS-type) symptoms on HRQOL in adult patients with CD reported for Northern Irish (6) and Swedish (9,25) patients on a longstanding GFD. However, the negative impact of IBS-type symptoms was small in the multivariate analysis compared with other determinants of HRQOL measured by a generic instrument, such as other comorbidities.
Our data offer support to the biopsychosocial model of IBS (1,2,11). In CD-associated IBS-type symptoms, we could identify clinical as well as psychological predictors. The finding that occasional nonadherence to a GFD predicted IBS-type symptoms is consistent with the clinical experience that even small amounts of gluten-containing food can provoke abdominal pain and diarrhea in some patients with CD (7,26). Yet, clinical factors cannot solely explain IBS-type symptoms in CD. We identified that mental disorder also predicts IBS-type symptoms in patients with CD. Because of the cross-sectional nature of our study, no conclusions can be drawn as to cause and effect—low HRQOL and high psychological distress may be the consequences of suffering from gastrointestinal symptoms as well as causes of these symptoms. Although 75% of the participants were women, the female gender proved to be a risk factor for IBS-type symptoms. Limited studies suggested that gender differences in visceral perception, cardioautonomic responses, gastrointestinal motility, and brain activation patterns to visceral stimuli exist in IBS. Gender differences in psychosocial factors have not been adequately studied (27).
Furthermore, our data underscore the necessity to differentiate between symptoms, function level (HRQOL), and healthcare-seeking behavior (12). Although our study showed a low number of patients with CD not seeking (medical and/or nonmedical) help, it is important to note that there are also nonconsulting irritable bowel-type patients with CD. Our hypothesis that healthcare use in CD-type IBS is determined by mental disorder and sociodemographic variables (gender, educational level) could not be confirmed. Other authors also found no influence of gender and mental status on healthcare-seeking behavior in patients with IBS (28). In accordance with the literature (13,28), we found that somatic comorbidities predicted healthcare seeking in German patients with CD and IBS-type symptoms. In contrast to the study of Vandvik et al. in a Norwegian primary care setting (13), we did not find a significant correlation between the amount of somatic comorbidity and probable mental disorder (HADS) (data not presented). A possible explanation of the impact of active medical comorbidities on IBS symptoms may be that medication, e.g., nonsteroidal agents because of musculoskeletal pain syndromes, could worsen gastrointestinal symptoms.
Some limitations of the study must be considered. a) The study population consisted of adult patients with CD who were recruited among members of the German Celiac Society, which may have induced a selection bias. However, there are no comparison data on patients with CD who belong to CD societies and those patients with CD who have no society membership. Furthermore, most patients with CD attending tertiary care outpatient departments in Germany are associated with the German Celiac Society. b) We cannot exclude a response bias of patients with CD with a reduced HRQOL who returned the questionnaires. There were no differences between the respondents and the whole membership directory of the German Celiac Society as to age and gender. Due to laws of data protection, a further comparison of respondents and nonrespondents was not possible. Therefore, our findings may not be representative for the general population of German patients with CD. Nonetheless, this group of patients represents the best available European representative sample studied. c) All data on the history and kind of diagnosis, CD-associated diseases, and medical comorbidities as well as adherence to regimen rely solely on the participants’ self-report. Due to data protection in this type of survey, information from clinical records, interviews, serologic tests, and endoscopy/duodenal biopsy was not available. Yet, the data on persistent gastrointestinal symptoms are consistent with those of patients with CD and with histologically proven remission reported by Swedish authors (9,25). Moreover, there is no correlation between histologic duodenal damage (villous atrophy) and the severity of clinical presentation (diarrhea) (29). d) Due to the type of study (postal survey), we could not use standardized psychiatric interviews for the confirmation of a psychiatric diagnosis when the critical cut-off scores of the HADS were reached. However, the sensitivity and the specificity of the HADS of 75% (with a cut-off value >8) for the diagnosis of a mental disorder, established by a structured interview according to the criteria of the Diagnostic and Statistic Manual for Psychiatric Diseases III-R, were demonstrated in patients with chronic inflammatory bowel disease (30). e) We did not examine patients for other somatic reasons of persistent gastrointestinal symptoms in CD, such as small intestinal bacterial overgrowth, chronic infection by Giardiasis lamblia or Ascaris lumbricoides, lactose intolerance, pancreatic insufficiency, collagenouos duodenitis, or colitis (31,32). Nor did we assess or control for details of the so-called GFD, for example, the inclusion of oats or industrially purified wheat-starch-based gluten-free products (26). f) We used the (old-fashioned) Rome I criteria of IBS because we intended to compare our data with other studies on CD and IBS. Presently, the only study by O’Leary et al. used the Rome I criteria (6). Furthermore, data on the prevalence of IBS symptoms in the general German population available were based on the Rome I criteria (18).
This study provides a basis for testing more specific hypotheses in relationship to the biopsychosocial model of "celiac IBS." Future psychophysiological studies in patients with CD and IBS should investigate if psychological distress leads to a prolongation of mucosal inflammation, reduced visceral pain threshold, or disturbed gastrointestinal motility (33). Interventional studies could reassess if appropriate psychotherapeutic treatment in cases of IBS-type symptoms and/or mental disorder could improve reduced HRQOL in adult patients with CD and IBS-type symptoms.
|
NOTES |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
Received for publication May 22, 2006; revision received October 29, 2006.
DOI:10.1097/PSY.0b013e318050d6bb
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONNOTESREFERENCES |
|---|
This article has been cited by other articles:
 |
|
 |
|
  C. Hausteiner, S. Bornschein, E. Bubel, S. Groben, C. Lahmann, M. Grosber, B. Lowe, F. Eyer, B. Eberlein, H. Behrendt, et al. Psychobehavioral Predictors of Somatoform Disorders in Patients With Suspected Allergies Psychosom Med, November 1, 2009; 71(9): 1004 - 1011. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
