Painful and Painless Constipation: All Roads Lead to (A Change in) Rome
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Disease classifications are useful to the extent that they facilitate an understanding of the pathophysiology, guide the diagnosis or treatment, or predict the natural history of the condition. In the field of gastroenterology (GI), disease classifications have long been used for functional syndromes that have largely eluded diagnosis based on conventional criteria such as histological, serological, or biochemical data. The Rome criteria classify chronic constipation as: functional constipation (FC), constipation-predominant IBS (IBS-C), and defecatory disorder (DD). FC is defined by the presence of two or more of six bowel symptoms such as excessive straining to defecate. IBS-C is defined by abdominal pain that is associated, in time, with bowel disturbances (harder or less frequent stools) and/or relief of pain with defecation. DD, which is defined by symptoms of FC or IBS-C combined with objective evidence of impaired rectal evacuation, respond to pelvic floor biofeedback therapy rather than to laxatives. Increased perception of visceral sensations is more prevalent in IBS-C than in FC [1]. The dose and the efficacy of medications such as lubiprostone or linaclotide differ between FC and IBS-C [2]. These features suggest that idiopathic constipation is not a homogenous entity, providing the raison d’être for classifying constipation according to response to therapy.
Many patients with FC have abdominal pain, which blurs the distinction between FC and IBS-C. Indeed, in one study, approximately 90% of patients with IBS-C also had criteria for FC and about 44% of the FC patients also had criteria for IBS-C [3]. In patients with overlapping symptoms, a single diagnosis is only possible because the Rome criteria require patients who have symptoms of IBS-C and FC to be designated as IBS-C and not as FC. Moreover, it can be challenging to distinguish between FC and IBS-C in clinical practice [4] because many constipated patients who have infrequent and hard stools even in the absence of abdominal pain are puzzled when asked to relate the hardness and frequency of their bowel movements with the presence of abdominal pain. Lastly, in approximately one-third of patients, symptoms shift over time from CC to IBS-C and vice versa [3]. Hence, the current Rome system for classifying chronic constipation as FC and IBS-C appears to lack specificity and reproducibility; a superior approach is necessary.
Characteristics of studies comparing painless and painful constipation
First author, year, country | Study design | Diagnosisa (number of patients) | Assessments | Threshold for abdominal pain | Key findings |
---|---|---|---|---|---|
Lanfranchi 1984, Italy [12] | Single center, clinic-based | Total 25 PFC (14) PLC (11) | Double contrast barium enema Proctosigmoidoscopy Intestinal transit time Anorectal manometry | Unspecified | In patients with PFC, constipation began at a later age; these patients had higher maximum resting anal pressure, normal rectal sensation, and normal colonic transit |
Bharucha 2006, USA [6] | Single center, Prospective study, Mail survey | Total (2738) Controls (2068) PLC (247) PFC (33) IBS-C (83) Non-C-IBS (214) Frequent abdominal pain (93) | Bowel symptoms (ROME II criteria) Quality of life Somatic symptoms | Abdominal pain occurring ≥ 1 day/week | PFC was less prevalent (1% PFC vs. 7% PLC) PFC patients had poorer general health and quality of life, more somatic symptoms, and more urinate urgency |
Drossman 2008, USA and Canada [7] | Multicenter, Retrospective analysis of a prospective clinical trial | Total (231) IBS-C (80) PFC (18) PLC (23) IBS-D (55) IBS-A (55) | Bowel symptoms (ROME II criteria) Healthcare utilization Quality of life | Abdominal pain severity ≥ 50 pain score on visual analog scale (VAS) | PFC patients had higher pain scores, poorer daily function, greater healthcare utilization, days in bed for illness, more procedures, and greater use of antidepressants |
Rey 2014, Spain [13] | Single center, Prospective study, Telephone survey | Total (1500) Controls (1136) PLC (209) PFC (30) IBS-C (49) Non-C-IBS (76) | Bowel symptoms (Rome III criteria) Laxative use Quality of life | Abdominal pain occurring ≥ 2 days/month | PFC and IBS-C patients were younger, reported more severe constipation and related symptoms, and greater laxative use |
Bouchoucha 2018, France [8] | Single center, Prospective study, Clinic visits | Total (546) PFC (230) PLC (316) | Bowel symptoms ROME III criteria) Psychometric evaluation Total and segmental colonic transit time Anorectal manometry | Abdominal pain severity ≥ 4 on a scale of 0–10 | PFC patients reported more severe symptoms (constipation and bloating), more depression, state and trait anxiety |
Continuing this theme, a meticulous study by Bouchoucha and colleagues in this issue of Digestive Diseases and Sciences not only evaluated symptoms, anxiety, and depression, but also colonic transit and anorectal manometry in 546 consecutive constipated patients referred to a tertiary center [8]. Of these 546 patients, 301 (53%) and 245 (47%), respectively, were classified as having FC and IBS-C. Based on the revised classification, 316 (58%) had “mild pain” and 230 (42%) had “painful” constipation. Approximately 80% of patients with FC but only one-third of patients with IBS-C had “mild pain” constipation. Hence, the “mild pain” and “painful” groups predominantly corresponded to patients with FC and IBS-C, respectively. Compared to “mild pain” constipation, patients with “painful” constipation had more prominent bowel symptoms and were more likely to have upper gastrointestinal (e.g., dysphagia and dyspepsia) and anorectal symptoms, urinary and sexual symptoms, anxiety and depression, and slower rectosigmoid transit. The widespread symptoms in painful constipation may partly reflect increased perception of visceral sensations such as wall tension [1].
Proposed revised classification of chronic constipation
Second, the symptom criteria for IBS-C should be revised, eliminating the need for criteria that solely rely on the relationship between abdominal pain and bowel disturbances. Both FC and IBS-C should be defined by bowel symptoms, respectively, without or with clinically significant abdominal pain. Ideally, the abdominal pain threshold should be easy-to-understand, universal, reproducible, should identify groups that are stable over time (i.e., minimizing switching between categories), should guide therapy such as medication dose, and should predict the response to therapy. Different abdominal pain thresholds have been used to discriminate between painless (or “mild pain”) and “painful” constipation (Table 1). Rather than using an arbitrary threshold, the study by Bouchoucha used a cluster analysis to uncover the threshold that best discriminated between groups. Then, this threshold (i.e., an abdominal pain severity score of 4 on a Likert scale from 0 to 10 in the past week) was used to separate patients into two groups: “mild pain” (i.e., pain score < 4) and “painful” (i.e., pain score ≥ 4) constipation. This threshold score of 4 or greater on a scale of 1–10 is similar to the US Food and Drug Administration (FDA) recommended eligibility criteria in IBS-C, i.e., a weekly average of worst daily abdominal pain score of ≥ 3.0 on a 0–10 scale [9]. The baseline pain severity score, which was evaluated on a 5-point scale (0–4), predicted the response to lubiprostone in IBS-C [10]. A baseline pain score of ≥ 3 on an 11-point scale (0–10) corresponds to a score ≥ 1.36 on a 5-point scale [9]. The response to lubiprostone was significantly better than placebo among patients in whom the baseline abdominal pain score was ≥ 1.5 and ≥ 2.0, but not in patients with a score ≥ 2.5 and ≥ 3.0 subgroups. By contrast, linaclotide benefited patients with severe symptoms, indeed, to a greater extent than in the overall intent to treat (ITT) population [11]. This suggests that the severity of abdominal pain predicts the response to therapy. Future studies should determine the stability of “painful” and “mild-pain” (or painless) constipation over time.
In summary, the study by Bouchoucha adds to the growing evidence that suggests a different approach to classifying constipation is necessary. In this instance, all roads lead to (a change in) Rome!
Footnotes
- 1.
Unlike the Rome criteria for IBS-C, the criteria for painful and painless constipation do not include the relationship between abdominal pain and bowel disturbances, the impetus for which originated from a factor analysis in which abdominal discomfort was associated with loose and/or frequent stools [5]. Those symptoms, which are characteristic of diarrhea-and not constipation-predominant IBS, were then reformatted (i.e., hard instead of loose stools, less frequent rather than more frequent bowel habits) to develop the criteria for IBS-C.
Notes
Funding
This study was supported by Grant RO1-DK078924 to Dr. Bharucha from the National Institutes of Health (NIH).
Author’s contribution
AEB and MS wrote the paper and approved the final version of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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