Irritable Bowel Syndrome: Toward an Understanding of Severity

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3:717–725

REVIEW Irritable Bowel Syndrome: Toward an Understanding of Severity ANTHONY LEMBO,* VANESSA Z. AMEEN,‡ and DOUGLAS A. DROSSMAN§ *Beth Israel Deaconess Medical Center, Boston, Massachusetts; ‡GlaxoSmithKline, Research Triangle Park, North Carolina; and §UNC Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina

Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that range in severity from mild and intermittent to severe and continuous. Although severity is a guiding factor in clinical decision making related to diagnosis and treatment, current guidelines related to IBS do not address the issue of severity. Recent data suggest that severity as a multidimensional concept, not fully explained by intensity of symptoms, has important clinical implications including health care utilization and health-related quality of life. Components of IBS severity include symptom intensity, time of assessment, whether the patient or physician makes the severity determination, the type of scale used to measure severity, and the degree of disability or impairment. Currently no consensus definition of IBS severity exists, although 2 validated scales of IBS severity have recently been published. Review of the literature suggests that the prevalence of severe or very severe IBS is higher than previously estimated with a range from 3%– 69%. Individual IBS symptoms are important but are not sufficient to explain severity. Rather, severity has multiple components including health-related quality of life, psychosocial factors, health care utilization behaviors, and burden of illness. However, studies have not been adequately designed to determine the relative values of these factors in IBS severity.

rritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurrent lower abdominal pain or discomfort that is associated with disturbed bowel function (ie, diarrhea, constipation, or alternating constipation and diarrhea) and feelings of abdominal distention and bloating.1 The severity of IBS, which we propose is a multidimensional concept that incorporates symptoms, disability, quality of life (QOL), and illness behaviors, has important implications for diagnostic evaluation and treatment and physicians’ attitudes and behaviors, all of which might impact clinical outcome. Although physicians intuitively assess IBS severity to plan diagnostic evaluation and treatment recommendations,1 few studies address this issue, and, to date, no

I

consensus criteria for assessing or defining IBS severity have been established. Historically, the distribution of patients by the severity of their IBS as determined by physicians has been thought to be 70% mild, 25% moderate, and 5% severe,2 although recent evidence and clinical experience suggest that the prevalence of moderate and severe IBS has been underestimated. The recent restriction by the Food and Drug Administration (FDA) of alosetron, a selective 5-hydroxytryptamine (5-HT3) receptor antagonist, to women with severe diarrhea-predominant IBS has highlighted the need for a better understanding of IBS severity.3 For the purpose of prescribing alosetron, severity of diarrheapredominant IBS was recommended to be 1 or more of the following symptoms: (1) frequent or severe abdominal pain or discomfort, (2) frequent bowel urgency or incontinence, or (3) disability or restrictions in daily life as a result of IBS. This definition of severity has yet to be validated and is unlikely to be applicable to all IBS patients, such as those without diarrhea. IBS severity is likely to be important in the decision on whether to use other IBS medications, especially those for which the risk benefit ratio is not well defined. The purpose of this article is to review and synthesize existing literature to identify the multiple factors contributing to severity and to make recommendations for future studies. Hopefully this will lead to clarification and possible consensus guidelines on the definition and assessment of severity in IBS.

Methods We conducted an English language literature search by using the MEDLINE, PsycLIT, HealthSTAR, Cochrane, and EMBASE databases for the time period 1966 through NovemAbbreviations used in this paper: FBD, functional bowel disorder; FBDSI, Functional Bowel Disorder Severity Index; FDA, Food and Drug Administration; IBS, irritable bowel syndrome; IBSSS, IBS Severity Scoring System; QOL, quality of life. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00157-6

718

LEMBO ET AL

Table 1. Manning Criteria Abdominal pain eased after bowel movement Looser stools at onset of pain More frequent bowel movements at onset of pain Abdominal distention Mucus per rectum Feeling of incomplete evacuation

ber 2004. Our search included the heading “colonic diseases functional” as well as combinations of key words such as “severity,” “severe,” and “severity of illness.” In addition, relevant studies were identified through a manual search of the references found online.

Significance of Severity It is difficult to understand the issue of IBS severity without first understanding the definitions for IBS per se and its historical development. The first diagnostic criteria, published in 1978 by Manning et al,4 identified 6 symptoms (Table 1) that were present more commonly in patients with IBS than in patients with other gastrointestinal diseases. Neither the duration nor the severity of symptoms was evaluated as a potential means of discriminating IBS from other gastrointestinal illnesses. Subsequent diagnostic criteria for IBS developed by consensus5 led to the Rome I criteria in 19926 and the Rome II criteria in 19997 (Table 2). Although IBS severity was not included in these criteria, duration and frequency of gastrointestinal symptoms were included for the first

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 8

time. Thus, it is evident that no effort has yet been made to address either the intensity of the symptoms or severity of the illness with regard to any classification system. Nevertheless, clinicians often choose to do so in making diagnostic and treatment decisions. Although neglected in the development of diagnostic criteria for IBS, recent studies have demonstrated the clinical importance of IBS severity. For example, in a study involving 126 IBS patients referred to a tertiary referral center specializing in functional bowel disorders (FBDs), Hahn et al8 found that patients who selfreported their IBS as severe or very severe incurred greater indirect medical costs (eg, decreased productivity and increased days in bed) and decreased health-related QOL (IBSQOL and SF-36) compared to patients who reported their IBS as mild or moderate. Likewise, in a study of 2613 Kaiser Permanente health maintenance organization patients, Longstreth et al9 found that patients who self-reported their symptoms of abdominal pain or discomfort as moderate or severe incurred 59% greater total healthcare costs than patients without IBS. In comparison, patients who self-reported their symptoms as mild symptoms of abdominal pain or discomfort incurred only 35% greater overall healthcare costs than patients without IBS. Several studies have also shown an association of IBS severity with reduction in health-related QOL. For example, in a multicenter study by Drossman et al10

Table 2. Rome I & II Criteria for IBS Rome I criteria At least 3 months of continuous or recurrent symptoms of the following: (1) Abdominal pain or discomfort Relieved with defecation, or Associated with a change in frequency of stool, or Associated with a change in consistency of stool Plus (2) Two or more of the following, at least on one fourth of occasions or days: Altered stool frequency (⬎3 bowel movements/day or ⬍3 bowel movements/day), or Altered stool form (lumpy/hard or loose/watery stool), or Altered stool passage (straining, urgency, or feeling of incomplete evacuation), or Passage of mucus, or Bloating or feeling of abdominal distention Rome II criteria 12 weeks or more, which need not be consecutive, in the past 12 months of abdominal discomfort or pain that has 2 of the following 3 features: Relieved with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool The following symptoms are not essential for the diagnosis, but their presence increases confidence in the diagnosis and might be used to identify subgroups of IBS: Abnormal stool frequency (⬎3/day or ⬍3/week) Abnormal stool form (lumpy/hard or loose/watery stool) in 1/4 of defecations Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation) in 1/4 of defecations Passage of mucus in 1/4 of defecations Bloating or feeling of abdominal distention ⬎1/4 of days

August 2005

involving 270 FBD patients recruited from 2 tertiary care centers and 2 gastroenterology clinics, IBS severity correlated with poorer physical functioning and healthrelated QOL (IBS-QOL), as well as greater healthcare usage. Likewise, Patrick et al11 found similar results in a study of 169 IBS patients recruited by advertisement and through gastroenterology clinics. A study by Coffin et al12 involving 858 IBS patients attending gastroenterology outpatient clinics in France found that the severity of IBS correlated with health-related QOL (GIQLI). Finally, Ricci et al13 studied 1426 IBS patients referred for a clinical trial from primary care and gastroenterology clinics. Patients with severe IBS had lower health-related QOL scores and incurred more direct medical costs. Interestingly, in this study patients whose IBS was mild or moderate underwent more diagnostic procedures, possibly reflecting a greater diagnosis uncertainty in these patients. All of these studies emphasize the importance of severity in clinical outcomes, especially QOL, and also has implications for public health, including the burden of illness.

Components of Severity in Irritable Bowel Syndrome Although no consensus on the standard for measuring severity exists, a global assessment of IBS severity (eg, wherein the patient is asked, “Rate the severity of your symptoms”) is an attractive measure. Similar to self-report global measures in clinical trials and QOL assessments, it encompasses one’s experience of a wide range of symptoms and bothersome factors that contribute to the self-perception of severity. This global measure is composed of several components. Symptom intensity is important, but not sufficient, to assess severity. In the study by Hahn et al,8 patients who perceived their IBS symptoms to be moderate or severe reported similar IBS symptoms with the exception of the sensation of unpassed stool, which was more common in patients with severe IBS. Similarly, Sach et al14 compared 128 IBS patients whose predominant symptom was abdominal pain to 52 patients whose predominant symptom was not pain. Interestingly, patients in both groups rated their IBS as being equally severe and reported similar degrees of psychological distress, impaired QOL, and increased healthcare use. Lembo et al15 found in a study of 443 IBS patients that self-rated IBS severity did not correlate with the presence, predominance, or temporal characteristics of abdominal pain. Finally, in a study by Ameen et al16 involving 2456 women with diarrhea-predominant IBS participating in a clinical

IBS SEVERITY

719

trial, physician-rated severity correlated with patientrated pain severity and IBS QOL. Abdominal pain is the most commonly used symptom to measure IBS severity because it is a strong predictor of patient status and healthcare seeking17,18 and is a prominent characterizing feature of IBS when populationbased surveys are done that involve factor analysis of symptoms.19 However, other symptoms, such as diarrhea, constipation, urgency, or bloating, can also be used to assess severity but would not be relevant to a wide range of IBS patients who do not have those particular symptoms. For example, fecal incontinence, or the frequency of diarrhea or urgency, which can have significant impact on patients’ QOL, has been used for studying diarrhea-predominant IBS, but this measure would not apply for patients with constipation-predominant IBS. Nongastrointestinal symptoms such as fibromyalgia, refractoriness to therapy, pain behaviors (ie, healthcare seeking), health-related QOL,13,20,21 and disability related to the symptoms or illness8 have also been used to assess IBS severity, although the utility of these measures relative to global assessments or self-perceived pain has not been explored satisfactorily. The time window for assessing severity is also an important feature of severity assessment. Retrospective assessments require patients to summarize the severity of fluctuating symptoms over variable periods of time. Symptom recall over more distant periods of time is likely to be inaccurate, with current or recent symptoms influencing judgment of previous symptoms, a phenomenon particularly notable in patients with chronic pain symptoms such as IBS.22 Although assessing only recent symptoms could potentially circumvent this problem, however, an accurate estimate of chronic symptoms would be difficult and not necessarily representative of overall severity because IBS symptoms fluctuate frequently. Whether the patient or physician makes the severity determination will also affect the results. A recent study addressed both physician and patient perceptions of the seriousness of illness and degree of disability in patients making night or weekend emergency phone calls to gastroenterology fellows. Physicians rated 23% of the patient calls as serious and considered 25% of the patients disabled, whereas 65% of patients rated their problem as serious and 53% believed themselves to be disabled (P ⬍ .0001 for both conditions).23 Moreover, the difference in perception of severity of symptoms between physicians and patients was far greater in patients with FBDs than in patients with organic disease. In patients with functional gastrointestinal disorders,

720

LEMBO ET AL

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 8

Table 3. Validated Measures of IBS Severity FBDSI These questions are read with the subject, and the answers are recorded, (1) On the line below, please place a vertical mark (/) that indicates the amount of abdominal pain you feel today: none (0) -------------------------------------------------------------------------------------------------------------------------------(100) very severe (2) Have you ever received a diagnosis of chronic functional abdominal pain? Yes ⫽ 1 No ⫽ 0 (3) How many visits have you made to your doctor for your bowel symptoms in the past 6 months? visits Add the subtotals to give the FBDSI Severity scores were defined as follow: ⬍37, mild; 37–110, moderate; and ⬎110, severe. IBSSS

Score ⫻ Factor ⫽ Subtotal ⫻1

⫽

⫻ 106 ⫽ ⫻ 11 ⫽

Score ⫻ Factor ⫽ Subtotal (1a) Do you currently (over the past 10 days) suffer from abdominal (tummy) pain? Yes No (1b) If yes, how severe is your abdominal (tummy) pain? 0| ----------------------------------------------------------------------------------------------------------------------------------------------------------------------|100 No pain Not very severe Quite severe Severe Very severe (1c) Please enter the number of days that you get pain in every 10 days. For example, if you enter 4, it means that you get pain 4 out of every 10 days. If you get pain every day, enter 10. Number of days with pain ⫻ 10 ⫽ (2a) Do you currently (over the past 10 days) suffer from abdominal distention* (bloated, swollen, or tight tummy)? Yes ⫽ 1 No ⫽ 0 (2b) If yes, how severe is your abdominal distention/tightness? 0| ----------------------------------------------------------------------------------------------------------------------------------------------------------------------|100 No distention Not very severe Quite severe Severe Very severe (3) How satisfied are you with your bowel habit? 0| ----------------------------------------------------------------------------------------------------------------------------------------------------------------------|100 Very happy Quite happy Unhappy Very unhappy (4) Please indicate with a cross on the line below how much your irritable bowel syndrome is affecting or interfering with your life in general. 0| ----------------------------------------------------------------------------------------------------------------------------------------------------------------------|100 Not at all Not much Quite a lot Completely Add the subtotals to give the IBSSS Mild, moderate, and severe were defined as scores of 75–175, 175–300, and ⬎300, respectively.

physicians perceived only 3% of the problems as serious (compared to 78% by the patients) and viewed only 6% of the patients to be disabled (compared to 69% by the patients). These findings are noteworthy in light of the health outcome data that show that patients with FBDs have greater pain scores, psychosocial difficulties, healthcare utilization, physician visits, and surgeries and poorer QOL24 than patients with an organic disease. Although patient perception of severity is preferred, it might be confounded by psychosocial distress, which might amplify severity. Thus, it might be necessary to adjust for psychological factors when determining patient scores of severity, particularly in patients with more severe symptoms. The type of scale used to measure severity can also influence the response. The most commonly used scales are linear and ordinal scales. Linear scales, such as a visual analogue scale or numeric scale, typically use a line of

fixed length (usually 100 mm) on which the patient can mark the magnitude of the symptoms. The line is anchored by descriptors indicating zero magnitude on the left and maximum magnitude on the right as in the case of the visual analogue scale or might contain multiple descriptors associated with numeric values as in the case of the numeric scale. Ordinal scales include individual categories from which the patient can choose the intensity of the symptoms by numbers or words. One example is a Likert scale, which uses verbal descriptors (eg, very mild, mild, moderate, severe, very severe). Most studies use 5 and 7 categories, although few have been well validated with regard to the magnitude of difference between categories. The superiority of one method over another has not been established. The advantage of a linear (eg, visual analogue scale) scale is that parametric analyses can be done (eg, linear regression, means, t tests), but it is sometimes difficult for patients to

August 2005

understand the task of entering their scores. In comparison, ordinal scales, including Likert scales, are intuitively easier for patients to understand, but the methods of analysis are more limited. Finally, the degree of disability or impairment is another factor that will influence IBS severity. A recent study of 133 patients meeting the Rome II criteria for IBS found that those patients who reported their symptoms as severe had significantly more work productivity loss and activity impairment and tended to miss more work time than patients who reported milder IBS severity.25

Validated Measures of Irritable Bowel Syndrome Severity There are 2 validated measures of severity, each with its strengths and limitations. The Functional Bowel Disorder Severity Index (FBDSI)26 includes 3 clinical factors that were shown to significantly predict the physician’s rating of severity: (1) patient perception of the intensity of current abdominal pain by using a visual analogue scale, (2) number of physician visits in previous 6 months, and (3) existence of constant or frequently recurrent and disabling pain (Table 3). The FBDSI has been used in several studies,20,27,28 thus providing normative information for a variety of populations. It is relatively easy to use, has been found reliable, has achieved some psychometric validation,23 and can be administered by a physician or patient. The FBDSI is helpful when doing comparative analyses between groups or for stratifying patients for clinical studies. This measure is strongly correlated at the more severe levels with psychosocial distress.23 The limitations of the FBDSI include the lack of specific IBS symptoms such as bowel function and the lengthy period of assessment (eg, healthcare visits are assessed during a period of 6 months, and the pain must be chronic to achieve a more severe score). This does not allow for responsiveness testing, because the score cannot change during short periods of time and would be confounded in a clinical trial as a result of structured visits. Also, the FBDSI is a measure of an individual’s pain experience and behavior more than a comprehensive composite of IBS symptoms and their change. The IBS Severity Scoring System (IBSSS)29 assesses 5 clinically relevant items during a 10-day period: (1) severity of abdominal pain, (2) frequency of abdominal pain, (3) severity of abdominal distention or tightness, (4) dissatisfaction with bowel habits, and (5) interference of IBS with life in general (Table 3). Each item is scored on a scale from 0 –100, and the score is calculated by

IBS SEVERITY

721

taking the sum of these 5 items. Unlike the FBDSI, the IBSSS evaluates the intensity of the primary IBS symptoms, is patient based, and appears responsive to change during a short period of time. The short time window (during the past 10 days) makes it valuable for treatment trials, and preliminary results suggest that it is more effective than “satisfactory relief” in defining a treatment responder.30 Therefore, the IBSSS could be considered for selecting patients with symptom exacerbation for clinical trials and to measure their change in response to treatment as an outcome. Limitations of the IBSSS include its inability to accurately represent overall illness severity, especially in patients whose symptoms frequently fluctuate.

Factors Associated With Severity in Irritable Bowel Syndrome Irritable Bowel Syndrome Subtype A study by Schmulson et al31 found no significant difference in patient-reported severity between patients with constipation- and diarrhea-predominant IBS. However, the study by Coffin et al12 found that IBS severity differed between patients with constipation, diarrhea, or alternating bowel habit, with constipation-predominant IBS reporting the greatest severity and diarrhea the lowest. This study differs from the previous study in that patients were assessed with the IBSSS and were recruited from gastroenterology clinics rather than a tertiary care center and advertisement. Gender In some, but not all, studies women exhibit greater IBS severity than men. In a study by Lee et al,32 patient-reported severity of IBS symptoms and intensity rating of abdominal discomfort and pain were similar between men and women. Women, however, reported bloating, distention, nausea, and incomplete evacuation as well as nongastrointestinal symptoms (such as urinary urgency and muscle aches) more commonly than men. In contrast, the study by Coffin et al12 found women to have more severe IBS than men, with intensity of abdominal pain and bloating reported as particularly more severe in women. A study by van der Horst et al33 included 109 IBS patients from primary care clinics and 86 patients from university internal medicine outpatient clinics. The following symptoms were rated on a scale from 0 –3: (1) frequency of abdominal complaints, (2) interference with daily activities, and (3) avoidance behavior as a result of the complaints. A severity score was calculated by the sum of these symptom scores. Women attending the

722

LEMBO ET AL

outpatient clinics had a higher severity score than did men attending the same clinics. Interestingly, women and men attending the primary care clinics had the same severity. Age A preliminary study by Palsson et al34 involved 826 patients diagnosed with an FBD in primary care and gastroenterology clinics. IBS severity was measured by using the IBSSS. Interestingly, in this study IBS symptom severity and impairment in health-related QOL was less among older (postmenopausal) female IBS patients compared with younger female IBS patients. Furthermore, women younger than 50 years had significantly higher IBS severity scores compared to same age men, but these differences disappeared in older age groups when the severity scores in women were reduced. Similar differences were not seen in male IBS patients. Menses IBS symptoms are frequently exacerbated by menstrual periods.35 Therefore a single assessment of severity during relatively short periods, as for example with the IBSSS, which assesses symptoms only during the past 10 days, might not accurately reflect overall severity of illness. Visceral Hypersensitivity Although one would assume that lower visceral sensation thresholds would be associated with more illness severity, IBS severity (moderate and severe) as measured by the FBDSI only weakly correlated with visceral hypersensitivity to rectal balloon distention.10 Likewise, in another study, IBS severity did not predict the development of rectal hypersensitivity to repetitive sigmoid distention.15 Psychosocial Psychological factors are intrinsically associated with IBS and symptoms in a large percentage of patients. Two studies have explored the relationship between IBS severity and psychosocial factors. In the study by Drossman et al10 patients with severe FBD showed greater pain scores and psychological distress than patients with moderate FBD as measured by the Beck Depression Inventory, the Overall Scale of the Sickness Impact Profile, and most subscales of the Sickness Impact Profile. They also exhibited more of a maladaptive catastrophizing coping style and less perceived ability to decrease or control their symptoms. There was a trend for a difference between the 2 groups when psychological distress was measured by symptom checklist 90, revised (SCL-

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 8

90R), and there was no significant difference for the Neuroticism scale of the NEO Inventory. In the study by Hahn et al,8 IBS severity was also not related to psychological symptom severity as measured by the SCL-90R. Taken together these studies suggest that patientperceived severity of IBS is determined by the limitations imposed by the disease as a whole and its psychosocial correlates rather than by the individual symptoms. These data suggest that patients with severe IBS are more likely to have psychosocial disability that needs to be addressed clinically to effect a positive outcome. Conflicting study results also illustrate the need for a consensus definition of IBS severity and uniform criteria by which patients and physicians can assess and assign severity of IBS, which can be helpful in directing treatment approaches and ultimately provide realistic expectations for clinical outcomes.

Distribution of Severity in Irritable Bowel Syndrome An often quoted article on IBS severity by Drossman and Thompson2 estimated the prevalence of IBS severity as 70% mild, 25% moderate, and 5% severe. Patients with mild IBS were thought to be seen predominantly in primary care, to have symptoms that correlated well with physiologic factors (eg, eating, defecation, menses, etc), and to have little association with psychosocial distress or high health care use. Patients with moderate IBS were seen predominantly in secondary care. Patients with severe IBS were thought to have more severe (and at times constant) pain, low correlation of pain with physiologic function, high healthcare use, and greater illness behavior, activity disruption, and psychosocial disturbances. Although the determinants of severity (especially psychosocial, symptom behavior, pain, and healthcare usage) used in this review were later confirmed by subsequent studies,13,28,36 the prevalence of more severe IBS might have been underestimated. Table 4 summarizes studies reporting the prevalence of IBS severity from mild to severe or very severe. The wide range of prevalence reported in these studies highlights the importance of patient referral source, type of scale or criteria used to assess severity, and whether the patient or physician performs the assessment. The prevalence of IBS severity reported in these studies is also significantly higher than previous estimates. The study by Longstreth et al37 studied patient characteristics from 3 different referral sources: primary care, patients responding to a newspaper advertisement for clinical trials in IBS, and a gastroenterologist in the Kaiser Permanente HMO practice. The percentage of

August 2005

IBS SEVERITY

723

Table 4. Prevalence of IBS Severity First author Hillila42

Coffin12 Francis29 Longstreth9 Longstreth37

Sach14 Hahn8 Liu38 Drossman26 Ricci13

No. of patients

Diagnosis of IBS

600

(1) Manninga (2) Rome I (3) Rome II Rome II Clinical Rome I Rome I

858 61 588 (1) 121 (2) 72 (3) 52 256 112 101 270 1426

Rome II Rome I Rome I Rome II

Person rating severity

Type of scale used

Community

Patient

Pain or discomfortb

GI clinic GI clinic PCd (1) PC (2) Adv (3) GI clinic TC and Adv TC GI Clinic (1) TC and GI clinic PC and GI clinic

Patient MD Patient Patient

IBSSS IBS severityb Pain or discomfortb Symptom severitye

8.3 16.4 29.6

Patient Patient

Symptom severitye Symptom severitye

MD MD

IBS severityf IBS severityf

5 6 19 26 15

Source of patients

Mild (%)

Moderate (%)

Severe or very severe (%)

(1) 73c (2) 56c (3) 56c 41.3 42.6 45.7 (1) 87 (2) 97 (3) 77 38 25 52 55 23

(1) 27 (2) 44 (3) 44 50.4 40.9 24.7 (1) 13 (2) 3 (3) 23 56 69 24 19 62

GI, gastrointestinal; PC, primary care; Adv, advertisement; TC, tertiary care. or more Manning criteria. bAbdominal pain or discomfort as measured on a 4-point Likert Scale (mild, moderate, severe, or very severe). cPatients with mild IBS undergoing flexible sigmoidoscopy at Kaiser Permanente HMO. dPatients with moderate IBS undergoing flexible sigmoidoscopy at Kaiser Permanente HMO. eSymptom severity was rated as moderate (sufficient to interfere with normal activities) or severe (incapacitating with inability to perform normal activities). fIBS severity was rated by physicians as mild, moderate, or severe. a2

patients who reported their IBS to be severe or very severe was lower in the group responding to advertisement (3%) than in patients in a primary care setting (13%) or patients being referred to a gastroenterologist (23%). Studies8,14 that included patients being referred to a tertiary care center with expertise in FBD report the prevalence of severe or very severe IBS to be between 57%14 and 69%.8 A number of studies of patients participating in clinical pharmacologic trials from referral gastroenterology practices38 – 41 reported the prevalence of severe IBS to be between 19%13 and 34%.40 Finally, Coffin et al12 recently reported the prevalence of severe IBS to be 50% among patients attending gastroenterology outpatient clinics in France. These data support the generally held concept that IBS severity varies significantly with the source from which patients are recruited. Patients with the most severe illness are found in tertiary care centers specializing in IBS, whereas patients with the mildest form of IBS are found in the community or through advertisement.

Summary IBS severity has important clinical and public health implications. However, few studies have been performed to address this issue, and, to date, no consensus criteria for assessing or defining IBS severity have been established. In the literature, IBS severity has been determined by a variety of factors including overall pa-

tient assessment, IBS symptoms, extraintestinal symptoms, pain behaviors such as healthcare seeking, healthrelated QOL, disability due to symptoms, and refractoriness to treatment. Our literature review of IBS severity reveals the following: (1) Recent estimates of the prevalence of severe or very severe IBS range from 3%– 69%, depending in part on the population surveyed. The prevalence of severe IBS might be significantly higher than previously estimated. (2) Individual IBS symptoms are important but are not sufficient to explain severity. (3) Severity must be understood from a broader multicomponent contruct that would include healthrelated QOL, psychosocial factors, healthcare utilization behaviors, and burden of illness that appear to be associated with IBS severity. Studies have not been adequately designed to determine the relative values of these factors in IBS severity. (4) To perform adequate studies on IBS severity the following factors must be considered. (a) Differences in perception of severity of symptoms between physicians and patients are far greater in patients with FBDs than in patients with organic disease. Although patient self-perception of severity is preferred, it might be confounded by psychological distress.

724

LEMBO ET AL

(b) The influence of age, gender, menopausal status, and duration of illness on IBS severity has not been well studied but might be associated with IBS severity. (c) The clinical setting, definition, and measurement used to assess severity also appear to influence IBS severity. (d) IBS symptoms should include an assessment of the patient’s ability to function, symptom intensity, psychological distress, a measure of the degree of disability caused by IBS symptoms, determination of IBS-specific QOL, and illness behaviors encompassing healthcare utilization. (e) Future studies should integrate the perception of severity by patient and physician and assess the influence of frequency and duration of symptom exacerbations, predominant bowel symptom, age, duration of illness, most bothersome symptom, and gender on IBS severity. (f) The representativeness of the most recent symptom exacerbation in assessing overall severity should be considered. (g) Epidemiology studies with a standardized scale are needed to determine population-based prevalence of IBS severity. (h) Future treatment trials in IBS should include a measure of severity to assess for potential differences in therapeutic and placebo efficacy. To date no studies have been adequately designed to encompass the multidimensional components of IBS severity. The development of instruments to measure IBS severity and identify independent predictors of severity would ultimately be helpful to clinicians to be able to better direct treatment approaches and predict response to therapy.

References 1. Drossma DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123: 2108 –2131. 2. Drossman DA, Thompson WG. The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med 1992;116:1009 –1016. 3. Lembo A, Weber HC, Farraye FA. Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder. Drugs 2003;63:1895–1905. 4. Manning AP, Thompson WG, Heaton KW, et al. Towards positive diagnosis of the irritable bowel. Br Med J 1978;2:653– 654. 5. Thompson W, Dotevall G, Drossman D, et al. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterology Int 1989;2:92–95. 6. Thompson W, Creed F, Drossman D, et al. Functional bowel disorders and chronic functional abdominal pain. Gastroenterol Int 1992;5:75–91.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 8

7. Thompson WG, Longstreth GF, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gut 1999; 45(Suppl 2):II43–II47. 8. Hahn BA, Kirchdoerfer LJ, Fullerton S, et al. Patient-perceived severity of irritable bowel syndrome in relation to symptoms, health resource utilization and quality of life. Aliment Pharmacol Ther 1997;11:553–559. 9. Longstreth GF, Wilson A, Knight K, et al. Irritable bowel syndrome, health care use, and costs: a US managed care perspective. Am J Gastroenterol 2003;98:600 – 607. 10. Drossman DA, Whitehead WE, Toner BB, et al. What determines severity among patients with painful functional bowel disorders? Am J Gastroenterol 2000;95:974 –980. 11. Patrick DL, Drossman DA, Frederick IO, et al. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci 1998;43:400 – 411. 12. Coffin B, Dapoigny M, Cloarec D, et al. Relationship between severity of symptoms and quality of life in 858 patients with irritable bowel syndrome. Gastroenterol Clin Biol 2004; 28:11–15. 13. Ricci J, Jhingran P, Harris W, et al. Impact of differences in severity of irritable bowel syndrome (IBS) on patients’ well being and resource use. Gastroenterology 2001;120:A406. 14. Sach J, Bolus R, Fitzgerald L, et al. Is there a difference between abdominal pain and discomfort in moderate to severe IBS patients? Am J Gastroenterol 2002;97:3131–3138. 15. Lembo T, Naliboff B, Munakata J, et al. Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroenterol 1999;94:1320 –1326. 16. Ameen V, Gordon S, Heath A, et al. Symptom severity in women with diarrhea predominant IBS. Am J Gastroenterol 2004; 99:A844. 17. Sandler RS, Drossman DA, Nathan HP, et al. Symptom complaints and health care seeking behavior in subjects with bowel dysfunction. Gastroenterology 1984;87:314 –318. 18. Heaton KW, Ghosh S, Braddon FE. How bad are the symptoms and bowel dysfunction of patients with the irritable bowel syndrome? a prospective, controlled study with emphasis on stool form. Gut 1991;32:73–79. 19. Whitehead WE, Crowell MD, Bosmajian L, et al. Existence of irritable bowel syndrome supported by factor analysis of symptoms in two community samples. Gastroenterology 1990; 98:336 –340. 20. Drossman DA, Patrick DL, Whitehead WE, et al. Further validation of the IBS-QOL: a disease-specific quality-of-life questionnaire. Am J Gastroenterol 2000;95:999 –1007. 21. Luscombe FA. Health-related quality of life and associated psychosocial factors in irritable bowel syndrome: a review. Qual Life Res 2000;9:161–176. 22. Naliboff BD. Choosing outcome variables: global assessment and diaries. Gastroenterology 2004;126:S129 –S134. 23. Dalton CB, Drossman DA, Hathaway JM, et al. Perceptions of physicians and patients with organic and functional gastrointestinal diagnoses. Clin Gastroenterol Hepatol 2004;2:121–126. 24. Drossman DA, Li Z, Leserman J, et al. Health status by gastrointestinal diagnosis and abuse history. Gastroenterology 1996; 110:999 –1007. 25. Reilly MC, Bracco A, Ricci JF, et al. The validity and accuracy of the Work Productivity and Activity Impairment questionnaire: irritable bowel syndrome version (WPAI:IBS). Aliment Pharmacol Ther 2004;20:459 – 467. 26. Drossman DA, Li Z, Toner BB, et al. Functional bowel disorders: a multicenter comparison of health status and development of illness severity index. Dig Dis Sci 1995;40:986 –995. 27. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo

August 2005

28.

29.

30.

31.

32.

33.

34.

35.

36.

for moderate to severe functional bowel disorders. Gastroenterology 2003;125:19 –31. Sperber AD, Carmel S, Atzmon Y, et al. Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia. Am J Gastroenterol 2000;95:995–998. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997; 11:395– 402. Whitehead W, Palsson O, Levy R, et al. Satisfactory relief is an unsatisfactory method of defining IBS treatment response. Gastroenterology 2004;126:A88. Schmulson M, Lee OY, Chang L, et al. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol 1999;94:2929 –2935. Lee OY, Mayer EA, Schmulson M, et al. Gender-related differences in IBS symptoms. Am J Gastroenterol 2001;96: 2184 –2193. van der Horst HE, van Dulmen AM, Schellevis FG, et al. Do patients with irritable bowel syndrome in primary care really differ from outpatients with irritable bowel syndrome? Gut 1997;41: 669 – 674. Palsson O, Whitehead W, Barghout V, et al. IBS severity and health-related quality of life improve with age in women but not in men (abstr). Am J Gastroenterol 2003;98:S272. Heitkemper MM, Cain KC, Jarrett ME, et al. Relationship of bloating to other GI and menstrual symptoms in women with irritable bowel syndrome. Dig Dis Sci 2004;49:88 –95. Creed F. The relationship between psychosocial parameters and

IBS SEVERITY

37.

38.

39.

40.

41. 42.

725

outcome in irritable bowel syndrome. Am J Med 1999;107: 74S– 80S. Longstreth GF, Hawkey CJ, Mayer EA, et al. Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials. Aliment Pharmacol Ther 2001; 15:959 –964. Liu JH, Chen GH, Yeh HZ, et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol 1997;32:765–768. Lucey MR, Clark ML, Lowndes J, et al. Is bran efficacious in irritable bowel syndrome? a double blind placebo controlled crossover study. Gut 1987;28:221–225. Luttecke K. A three-part controlled study of trimebutine in the treatment of irritable colon syndrome. Curr Med Res Opin 1980; 6:437– 443. Prior A, Whorwell PJ. Double blind study of ispaghula in irritable bowel syndrome. Gut 1987;28:1510 –1513. Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther 2004;20:339 –345.

Address requests for reprints to: Anthony Lembo, MD, 330 Brookline Avenue, Dana 501, Boston, Massachusetts 02215. e-mail: alembo@ bidmc.harvard.edu; fax: 617-667-2767. Supported in part by GlaxoSmithKline and by grants 1R01 AT01414-01 and 1R21 AT002860-01 from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (to A.L.). Drs Lembo and Drossman have served as consultants to GlaxoSmithKline. Dr Ameen is an employee of GlaxoSmithKline.