The cause of IBD has yet to be identified, but it is considered to develop as the result of abnormal intestinal immunity and altered gut microbiota caused by environmental factors such as diet and infection in genetically susceptible individuals. The two major forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). UC is a diffuse non-specific inflammatory disease of unknown cause that continuously affects the colonic mucosa proximal from the rectum and often forms erosions and/or ulcers.
CD is a chronic inflammatory disease of unknown cause, characterised by discontinuously affected areas with transmural granulomatous inflammation and/or fistula. CD can affect any region in the digestive tract from the mouth to the anus but is more likely to involve the small and large intestines (especially the ileocecum) and the perianal region.
Up to 80% of IBD patients have diarrhoea, note Anbazhagan et al. The British Society of Gastroenterology defines diarrhoea in terms of stool frequency, consistency, volume or weight. Chronic diarrhoea is defined as the abnormal passage of ≥3 loose stools per day for more than four weeks.
IBD-associated diarrhoea is multifactorial and is the outcome of intricate pathophysiological events arising from widespread and sustained mucosal inflammation.
Depending upon the site and magnitude of intestinal inflammation the severity of diarrhoea varies in IBD patients, ranging from increased bowel frequency to chronic diarrhoea requiring electrolyte supplementation and hospitalisation. The severity of diarrhoea (stool frequency and consistency) is thus considered as an important determinant of the disease activity index.
According to Barros et al, faecal incontinence (FI) is a commonly neglected symptom in IBD and is not infrequent to be referred as frequent bowel movements, urgency or tenesmus. FI is defined as involuntary faecal loss of liquid or stool.
Several reports have shown FI to have a significant negative impact on physical, social and emotional state of IBD patients. FI prevalence has been underestimated over the last decades due to social stigma, patient’s embarrassment and inadequate medical awareness. In a recent meta-analysis, Barros et al found that pooled prevalence of FI in IBD patients is 37%.
Rate of FI was similar among UC and CD patients. Higher risk of FI in IBD patients is likely due chronic changes in bowel habits, perianal disease/surgeries, loss of rectoanal inhibitory reflex and abnormal rectal sensation.
Diagnosis of FI requires a complete perianal examination, including inspection during Valsalva’s manoeuvres and digital rectal exam to evaluate sphincter tone at rest and squeeze.
Anorectal manometry is the gold standard to assess anorectal function, compliance, reflexes and sensation. In cases of suspected rectocele or anal sphincter defect further diagnostic testing with endoanal ultrasound and defecography might be considered.
Initial management includes better control of diarrhoea if present. Antidiarrhoeal drugs such as loperamide or diphenoxylate can be used as needed. Increasing fibre intake or bulking agents in IBD may be complicated with bloating and abdominal distention.
One study has shown that concomitant treatment with infliximab and surgical repair improved and maintained long-term continence in perianal CD patients. Anecdotal studies with percutaneous tibial nerve stimulation and pneumatic dilatation of the rectum have been done, but small sample size limits meaningful conclusions.
Injecting agents such as dextranomer gel and surgical procedures are contraindicated for IBD patients due to the risk of perianal abscess and fistula formation. Diverting loop colostomy could be acceptable when all above-mentioned therapies have failed.
Other agents to manage diarrhoea include bile acid binding resins such as cholestyramine, colestipol and colesevelam. These agents have been shown to be effective in controlling symptoms of bile acid malabsorption, also known as bile acid diarrhoea.
Schiller et al caution that these agents can have nonspecific constipating effects, bind to other medications, and the dosing schedule should ensure that they are taken more than two hours after other medications. Neither antibiotics nor probiotics are useful as nonspecific therapy in chronic diarrhoea.
Oral calcium supplementation also may treat mild chronic diarrhoea. Bismuth subsalicylate is a frequently used over-the-counter treatment for diarrhoea. However, there is some concern for safety with prolonged use. Bismuth also may be effective in the treatment of microscopic colitis.
Alosetron is a serotonin type 3 antagonist that slows colonic transit and increases fluid absorption. It is useful in diarrhoea-predominant and irritable bowel syndrome (IBS) and functional diarrhoea, but because of a risk of colonic ischaemia and severe constipation, it is used infrequently.
There is no simple and logical algorithm to govern the empiric treatment of chronic diarrhoea in every patient. Therefore, a thoughtful trial and error approach is frequently required to find the most effective therapy or combination of therapies for each patient, write Schiller et al.
The prevalence of constipation in patients with IBD is around 15% – similar to that of the general population, according to Barros et al. Patients with UC have higher rate of constipation compared to those with CD (25% vs 5.7%).
Assessment of constipation involves a comprehensive review of medical history and current medications to exclude secondary causes. In IBD patients, colorectal cancer is major a concern when addressing recent-onset constipation.
Dyssynergic defecation (DD) is a well-known cause of chronic constipation. However, in IBD patients it can also manifests with rectal discomfort, sensation of incomplete evacuation, diarrhoea or FI. DD is characterised by the discoordination between the contraction of abdominal wall and pelvic floor muscles that prevents adequate evacuation.
IBD patients have an increased risk of DD due to chronic changes in bowel habits, perianal disease and surgical procedures. Previous studies have reported IBD to be associated with sensorimotor anorectal function, increased anal pressure, increased rectal sensitivity and absent rectoanal inhibitory reflex.
In a recent meta-analysis Barros et al found a high prevalence rate from 45% to 97% in two studies with 182 IBD patients with ongoing GI symptoms. Diagnosis of DD in IBD patients is generally made based on anorectal manometry with a balloon expulsion test. Magnetic resonance/barium defecography and anal sphincter electromyography can also be utilised.
One other differential diagnosis to consider for constipation and IBS-like symptoms in IBD patients is Ehlers-Danlos Syndrome (EDS). EDS is a heterogeneous group of heritable connective tissue disorders and are grossly underdiagnosed.
EDS type III (hypermobility type) is the most common type and is associated with significant GI symptoms such as constipation, straining, abdominal pain, nausea, distention, pelvic floor dysfunction, heartburn, and IBS-like symptoms.
Diagnosis of EDS III is entirely clinical without any objective or genetic testing. The pathophysiology of GI symptoms in EDS patients remains unknown but visceroptosis, defined as prolapse of abdominal organs below their natural position, has been proposed as the cause of GI symptoms in EDS.
Therapy is symptom-directed and involves a multidisciplinary approach. Physiotherapy and promotility drugs have been indicated to treat gastrointestinal symptoms in these patients but, note Barros et al, clinical trials are lacking.
Non-pharmacological interventions such as exercise, increased fluid intake or soluble fibre have modest efficacy in the general population and may be considered in IBD patients. Polyethylene glycol, an osmotic laxative, is the first-line drug to treat constipation.
Prucalopride and tegaserod are selective serotonin type 4 agonists, which have been recently approved/reintroduced by the American Food and Drug Administration for treatment of constipation. However, caution Barros et al, the safety of these medications is yet to be determined in the IBD population.
Secretagogues are also effective in the treatment of constipation. In a recent meta-analysis, linaclotide, lubiprostone and plecanatide were all shown to be superior to placebo in treating constipation. The most common side-effects were diarrhoea and nausea.
For the last three decades biofeedback has been the standard treatment for DD and previous studies have reported high symptomatic response, reduced healthcare utilisation and improved overall quality of life (QoL).
Barros et al showed a response rate of 86% and 70% in patients with and without ileal pouch anal anastomosis, respectively. IBD patients with anal stricture, fissure and stenosis may have limited benefit from biofeedback therapy. Invasive procedures such as botulinum toxin injection are not recommended for IBD patients considering the increased risk of perianal fistula and FI.
IBD have a negative effect on the quality of QoL. The management of diarrhoea and constipation plays an important role in improving patients QoL. Various options are available to manage these two debilitating symptoms.
- Anbazhagan AN, Priyamvada S, Alrefai WA and Dudeja PK. Pathophysiology of IBD associated diarrhea. Tissue Barriers, 2018.
- Barros LL, Farias AQ, Rezaie A et al. Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment. World J Gastroenterol, 2019.
- Schiller LR, Pardi DS, Sellini JH et al. Chronic Diarrhea: Diagnosis and Management. Clinical Gastroenterology and Hepatology, 2017.