A comprehensive approach to inflammatory bowel disease

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Reference: September 2025 | Issue 9 | Vol 11 | Page 16

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Inflammatory bowel disease (IBD) is a chronic, immune-mediated disorder of the gastrointestinal tract, primarily classified into two main subtypes, namely ulcerative colitis (UC) and Crohn’s disease (CD). UC typically involves continuous inflammation that starts in the rectum and may extend proximally, predominantly affecting the colon.

In contrast, CD can affect any part of the gastrointestinal tract, from mouth to anus, and often presents with patchy, discontinuous areas of inflammation. In some cases, distinguishing between the two can be challenging, leading to a diagnosis of ‘indeterminate colitis’.

The pathophysiology of IBD is multifactorial, involving complex interactions between genetic susceptibility, environmental factors, epithelial barrier dysfunction, microbial, and immune factors.

Epidemiological data from Crohn’s and Colitis Ireland estimate around 40,000 individuals are living with IBD in Ireland, with an incidence of 5.9 new CD cases and 14.9 new UC cases per 100,000 population in 2011. Globally, approximately 6.8 million people were affected in 2017, nearly double the number estimated in 1990.

The diagnosis of IBD is established through a combination of clinical history, laboratory tests, endoscopic evaluation, and histological assessment. It is essential to rule out other causes of colitis, including infectious, ischaemic, radiation-induced, and medication-related (eg, NSAID-induced) colitis. Stool testing can help identify infectious pathogens and measure markers of inflammation, such as faecal calprotectin, which supports the diagnosis of IBD.

UC

UC can be classified based on the anatomical extent of disease: Proctitis, left-sided colitis, or pancolitis. Patients typically present with diarrhoea, which may be bloody or contain mucus, and often report urgency, abdominal cramping, and occasionally incontinence. Chronic blood loss can result in iron deficiency anaemia.

Acute severe colitis is defined as more than six bloody stools per day, accompanied by systemic signs such as tachycardia, hypotension, or fever. Acute complications include toxic megacolon and perforation. Those presenting with a flare are also at higher risk for the development of thromboembolism.

The severity of an ulcerative colitis flare may be classified using the Mayo Scoring system, which considers the stool pattern, rectal bleeding and endoscopic findings. During endoscopy, a mild colitis may have evidence of friability, erythema, and decreased vascularity. Moderate colitis will have worsening friability, erythema, loss of the vascular pattern, and erosions.

In severe colitis there will be ulceration and spontaneous bleeding. Chronic complications of UC include strictures, dysplasia, and colorectal cancer (CRC). European Crohn’s and Colitis Organisation (ECCO) guidelines report that the risk is highest for those with pancolitis. Other factors which increase the risk include disease activity, post-inflammatory polyps, and a positive family history.

In ECCO guidelines, colonoscopic surveillance is generally recommended from eight years after the onset of UC symptoms. Thereafter, the interval depends on the extent and severity of disease as well as additional risk factors. Patients with limited colitis affecting <50 per cent of the colon or those with mild endoscopic or histological inflammation require surveillance every five years. Those with extensive colitis with moderate to severe endoscopic or histological inflammation, post-inflammatory polyps, or a family history of colorectal cancer in a first-degree relative typically require three-yearly surveillance.

Annual colonoscopy is reserved for the highest-risk groups, such as those with strictures in the last five years or dysplasia (without previous surgery), primary sclerosing cholangitis, or a first-degree relative diagnosed with colorectal cancer before the age of 50. It is also important to note that those who have had surgery with a remaining rectal stump will also require surveillance.

Crohn’s disease

Common symptoms of CD include abdominal pain, diarrhoea, and weight loss. Given the nature of transmural inflammation in CD, fibrosis and strictures can result in obstructive presentations on occasion. Although CD can affect any area from the mouth to the anus, the majority of CD patients have disease affecting the small bowel such as the terminal ileum. Around one-third have perianal disease.

CD can be classified based on location, eg, ileal, colonic, ileocolonic, and isolated upper disease or based on behaviour eg, structuring or penetrating with or without perianal disease. Other important features to watch out for in CD include evidence of transmural inflammation which includes fistulating disease, abscess formation, and perianal disease.

Patients with CD, particularly small bowel CD, are also at high risk of malabsorption resulting from inflammation and loss of absorption, bile acid malabsorption, and, in some, small intestinal bacterial overgrowth.

CD is diagnosed as mentioned above, but sometimes imaging of the small bowel can be used as an adjunct, given that endoscopy is largely limited to the large bowel. Magnetic resonance enterography can be used to assess the small bowel and to assess any perianal disease.

The Simple Endoscopic Score for Crohn’s Disease (SES-CD) can be used to evaluate the severity of CD during endoscopy. It comments on the presence and size of ulcers, extent of ulcerated surface, and the presence and type of stenosis in five segments of the bowel. A score of >16 conveys a diagnosis of severe activity.

Complications of CD include strictures, fistula, abscess formation, and, more long-term, CRC. Risk factors which convey a poorer prognosis in Crohn’s include age at diagnosis <40, smoking, perianal or rectal involvement, and glucocorticoid-requiring disease.

For Crohn’s colitis, surveillance should begin around six to eight years after symptom onset. The frequency is then stratified according to risk: Patients with limited colonic involvement (<50% of the colon) or pancolitis with mild disease activity endoscopically or histologically may be monitored every five years. Those with more extensive or active disease endoscopically or histologically, post-inflammatory polyps, or CRC in a first-degree relative aged over 50, require three-yearly exams.

The highest risk individuals – including those with strictures, dysplasia in those who have declined surgery, concomitant primary sclerosing cholangitis, or an affected first-degree relative under 50 – should undergo annual colonoscopy.

Management

Management of both CD and UC involves an entire multidisciplinary team (MDT), including gastroenterologists, colorectal surgeons, IBD clinical nurse specialists, dieticians, radiologists, and pathologists.

Medical management of ulcerative colitis broadly involves induction and maintenance of remission. Initially, for flare management, a locally acting steroid such as budesonide (eg, Cortiment) in an MMX capsule, which is released locally in the distal colon, can be used for induction of remission. In a more severe flare, oral prednisolone or IV steroids may be required. Long-term or recurrent steroid usage is not encouraged due to the number of side effects related to same.

Mild to moderate UC may be controlled with 5-aminosalicylate therapy, either topical or oral. Topical may suffice for proctitis; however in left-sided or pancolitis, both topical and oral mesalamine may be required. Severe disease can require the use of immunomodulators such as azathioprine or 6-mercaptopurine, but in modern practice, often patients will step up to biologic therapy quite quickly.

Thiopurine methyltransferase (TPMT) levels should always be checked prior to commencement of these medications to reduce the risk of leucopenia associated with TPMT deficiency. Full blood count and liver function tests should also be monitored while on these medications given the risk of myelosuppression and hepatoxicity.

As mentioned, if disease is not controlled with the above, biologic or more immune-targeted therapies can be used. The use of biologic therapies has transformed the management of IBD over recent decades. However, the use of these drugs requires monitoring for complications of immunosuppression.

A biologic screen should always be performed prior to commencement of biologic therapy to reduce the risk of opportunistic infection and infection reactivation. A biologic screen includes HIV, hepatitis B and C, EBV/CMV serology, VZV titres, measles titres, Quantiferon, and a chest x-ray.

Biologic therapy options include:

– Anti-TNF: Infliximab (rescue therapy), adalimumab, and golimumab

• Infliximab with azathioprine (Imuran) combination can be used and is more effective than either alone
• Patients with anti-drug antibodies resulting in loss of response to their first anti-TNF agent, should be given combination therapy when trying a second anti-TNF agent
• Anti-integrin: Vedolizumab (blocks trafficking of neutrophils and lymphocytes to sites of inflammation) is gut specific and conveys fewer systemic side effects
• IL12/IL23 inhibitor: Ustekinumab
• IL23 (P19 subunit) inhibitors: Risankizumab and guselkumab.

For those with refractory UC, further biologic options include:

• JAK inhibitors: Tofacitinib, upadacitinib, filgotinib
• Sphingosine-1-phosphate (S1P) receptor inhibitors: Ozanimod, etrasimod.

Patients on triple immunosuppressive therapy (ie, combination therapy and steroid) should receive pneumocystic jirovecii prophylaxis.

Although less commonly required than before the advent of biologic medications, surgery is still a valid treatment option in appropriate circumstances. In acute severe colitis refractory to medical therapy, malignancy, or dysplasia, a subtotal colectomy with end ileostomy is often required.

It is important to note that up to 30 per cent of patients do not have a response to biologic therapy (primary non-responders) and, furthermore, some patients will lose an initial response to biologic therapy after time (secondary non-responders) and may require a change in treatment strategy.

Monitoring of drug levels and drug antibodies can be performed in these patients. Options to overcome this include alteration of the drug administration interval or dose, combination therapy with an immunomodulator, or switching to an alternative biologic. Alternatively, patients may require surgery or non-pharmacological treatments such as enteral nutrition, and pain and symptom control strategies.

Given that CD involves specific complications such as fistula and abscess formation, it is particularly important to outrule infection or abscess in CD prior to commencement of immunosuppressive therapy.

The treatment of Crohn’s similarly involves steroids for induction of remission or in an acute flare. Locally active steroids such as oral budesonide released in the right colon or terminal ileum (Entocort or Budenofalk) can be used in CD affecting the ileum.

In those with more severe disease, immunomodulators such as azathioprine and 6-mercaptopurine can be used.

Biologic therapies used in CD include:

• Anti-TNF: Infliximab and adalimumab for induction of remission
• IL12/IL23: Ustekinumab
• IL23 P19 subunit inhibiters: Risankizumab, guselkumab
• Anti-integrin therapy: Vedolizumab
• Infliximab + immunomodulator combination.

Surgery is more commonly required in CD and risk factors for the requirement of surgery include smoking, penetrating and structuring disease, ileal or jejunal disease, and young age at diagnosis. In presentations of bowel obstruction due to stricture formation or the development of a fistula, a surgical review is indicated. A surgical review is also indicated where there is suspicion of perianal disease which may require incision and drainage.

Non-medical therapy

Non-medical and surgical factors in the management of IBD includes risk factor modification and nutritional optimisation and this can be particularly important in paediatric and adolescent IBD. Nutritional optimisation involves electrolyte replacement, vitamin D supplementation, and iron supplementation as required. Enteral nutrition as mentioned earlier can also be used as a treatment strategy for penetrating or small bowel CD. This should be guided by dietician input through the MDT.

All patients with IBD should be encouraged to quit smoking and referred to smoking cessation services as required.

Monitoring of disease activity can be achieved by faecal calprotectin at three to six months following initiation of therapy. Endoscopy is also performed after six months to assess response.

Vaccination

Given the immunosuppressive nature of IBD treatment, it is important to remain vigilant regarding monitoring for opportunistic infection. ECCO guidelines published in 2021 advise vaccination for IBD patients against hepatitis A and B, herpes zoster, pneumococcus, and HPV (in both male and female patients), as well as annual influenza vaccine. Vaccination status should be checked at yearly intervals.

It is also advised that the routine vaccination programme for tetanus, diphtheria, pertussis, meningococcus, MMR, varicella, poliomyelitis, and SARS-CoV-2 is adhered to. Female patients with IBD should be advised to attend cervical screening.

Bone protection
Reduced bone density is common in patients with IBD due to factors such as glucocorticoid treatment, longstanding inflammation, and malnutrition. ECCO guidelines have previously advised that those on systemic steroid therapy should be prescribed calcium and vitamin D concomitantly.

Psychological support
Psychological support is a crucial component in the management of inflammatory bowel disease. It is essential to remain mindful of the impact that symptoms, disease-related complications, and the burden of intensive treatments can have on patients’ quality of life.

Integrating access to a clinical psychologist within the MDT provides invaluable support. Stress management, coping strategies, and empowering patients in the self-management of their condition are vital aspects of holistic care.

Further advances

Intestinal ultrasound can be used to monitor disease activity in patients with IBD. Features that can be assessed include the mucosal layer and the thickness of the bowel. A thickened, hypoechoic mucosal layer and transmural bowel thickening is indicative of active disease. Point of care ultrasound is non-invasive and relatively inexpensive and is becoming more widely used in recent years.