Specialist investigations

Specialist investigations to confirm the diagnosis of ulcerative colitis may include:

• Colonoscopy with histology of multiple intestinal biopsy specimens, which allows classification of disease extent and severity.
  • Typical macroscopic features of ulcerative colitis include signs of inflammation extending from the rectum proximally, with erythema, granularity, friability, purulent exudates, and ulceration. Histology findings may include crypt distortion, acute inflammatory changes of cryptitis, crypt abscesses, and infiltrative changes.
    • Note: 10–34% of children with new-onset ulcerative colitis lack typical histological features of chronic colitis at presentation [Oliveira, 2017].
• Upper intestinal endoscopy for children and young people.
  • This is important to differentiate Crohn's disease from ulcerative colitis, as Crohn's disease may not present with specific upper gastrointestinal symptoms. See the CKS topic on Crohn's disease for more information.
• Magnetic resonance enterography (MRE) of the small bowel and additional small bowel imaging.
  • This may be needed in children and adults where endoscopy and conventional imaging have been non-diagnostic, there are atypical symptoms, or there is a need to differentiate ulcerative colitis from Crohn's disease.
• Computed tomography (CT) to stage ulcerative colitis and look for extraluminal complications, such as abscesses and fistulas.
• Plain abdominal X-rays to identify colonic dilatation, which may indicate complications such as bowel obstruction and toxic megacolon.
• Abdominal ultrasound to assess bowel thickness and dilatation suggesting bowel obstruction, fistulas, and strictures.

[Sandhu, 2010; Ford, 2013; Levine, 2014; Fell, 2016; Oliveira, 2017; Turner, 2018a; Lamb 1, 2019; Segal, 2021]

Basis for recommendation

The recommendations on the management of suspected ulcerative colitis are largely based on the National Institute for Health and Care Excellence (NICE) clinical guideline Ulcerative Colitis: management [NICE, 2019] and the NICE quality standard for inflammatory bowel disease [NICE, 2020]; the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], the European Crohn's and Colitis Organisation (ECCO) consensus guidelines Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders [Magro, 2017] and The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease [Harbord, 2016], and expert opinion in a review article on ulcerative colitis [Ford, 2013].

• People with acute severe disease require emergency hospital admission for intensive management [Lamb 1, 2019].
• The suggested criteria for severe ulcerative colitis are based on the NICE clinical guideline [NICE, 2019].
• Urgent referral is indicated if a diagnosis of ulcerative colitis is suspected and the person does not have severe symptoms, as an accurate diagnosis is needed to allow optimal drug treatment for the induction and maintenance of remission, which should be initiated by a specialist [Magro, 2017]. This is in line with the NICE quality standards for inflammatory bowel disease, which recommend specialist assessment within four weeks of referral [NICE, 2020].
  • Colonoscopy biopsies are needed to determine disease extent, which influences treatment options, gives prognostic information, and determines the onset and frequency of colorectal cancer surveillance. Topical suppositories or enemas are usually the first-line choice for proctitis and left-sided colitis, respectively, whereas oral therapy (often combined with topical therapy) is appropriate for extensive colitis [Magro, 2017].
• The recommendation on arranging referral for suspected extra-intestinal manifestations is extrapolated from the BSG guideline [Lamb 1, 2019], and is pragmatic, based on what CKS considers to be good clinical practice.

Specialist treatments

• Specialist drug treatments for ulcerative colitis are generally given for induction and maintenance of remission. Individualized treatment options depend on the severity, extent, and pattern of disease, previous response to treatment, and the person's preferences. Options include:
  • Aminosalicylates — mesalazine and sulfasalazine may be considered for a mild-to-moderate first presentation or inflammatory exacerbation of ulcerative colitis. These drugs are also effective at maintaining remission. They are often prescribed topically (suppository or enema) initially, and orally if remission is not achieved. For extensive disease, topical and high-dose oral treatment may be offered first-line.
  • Corticosteroids — monotherapy with a time-limited course of corticosteroids may be used for induction of remission if aminosalicylates are ineffective or not tolerated, with the aim to gradually taper the dose according to disease severity and the person's response to treatment. They should not be used to maintain clinical remission due to the risk of multiple adverse effects with long-term use. They may be prescribed topically, orally, or intravenously.
    • The term 'corticosteroid dependency' usually relates to people with ulcerative colitis who are unable to stop corticosteroids within 3 months without recurrent active disease, or who have a relapse requiring corticosteroids within 3 months of stopping them.
  • Ciclosporin —  may be used for acute severe disease, especially if intravenous corticosteroids are not effective, contraindicated, or not tolerated.
  • Thiopurines — azathioprine or mercaptopurine may be considered to maintain remission in people using aminosalicylates who have required two or more courses of oral corticosteroids in the previous year or whose disease is steroid refractive or dependent.
    • Note: thiopurines may increase the risk of non-melanoma skin cancer, and people should be monitored for skin cancer and given appropriate sun protection advice.
  • Biologics and Janus kinase inhibitors — infliximab, adalimumab, golimumab, tofacitinib, ustekinumab, vedolizumab, filgotinib, and mirikizumab are used to induce or maintain remission in people with severe active disease in specific scenarios such as when conventional or other therapies are not working or not tolerated. The sphingosine-1-phosphate receptor modulator ozanimod is also an option.
  • For more detailed prescribing information, see the CKS topics on Corticosteroids - oral and DMARDs.
• Specialist enteral nutritional supplementation may be used as an alternative to conventional therapy in some children for induction of remission, including when:
  • Oral feeding is not tolerated or there is an acute severe flare with associated malnutrition.
  • There is faltering growth or development, or concerns about adverse effects of corticosteroids.

[NICE, 2015a; NICE, 2015b; Fell, 2016; Harbord, 2017; Oliveira, 2017; NICE, 2018]  [Turner, 2018a; Turner, 2018; Lamb 1, 2019; NICE, 2019; NICE, 2022b; NICE, 2022c; Bischoff, 2023; NICE, 2023]

Basis for recommendation

The recommendations on review in primary care are based on the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], the National Institute for Health and Care Excellence (NICE) clinical guideline Ulcerative Colitis: management [NICE, 2019], the European Crohn's and Colitis Organisation (ECCO) consensus guidelines Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders [Magro, 2017], Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management [Harbord, 2017], European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases [Dignass, 2015], The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease [Harbord, 2016], European Evidence-based Consensus: Inflammatory Bowel Disease and Malignancies [Annese, 2015], and Practical guideline for fatigue management in inflammatory bowel disease [Kreijne, 2016]; the joint ECCO and European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) evidence-based guidelines Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care [Turner, 2018a] and Management of Paediatric Ulcerative Colitis, Part 2: Acute severe colitis [Turner, 2018]; the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline Clinical nutrition in inflammatory bowel disease [Bischoff, 2023]; the British Society of Paediatric Gastroenterology, Hepatology, and Nutrition (BSPGHAN) consensus document Guidelines for the management of inflammatory bowel disease in children in the United Kingdom [Sandhu, 2010], and expert opinion in review articles on ulcerative colitis [Ford, 2013; Fell, 2016] and inflammatory bowel disease in children [Rosen, 2015; Oliveira, 2017].

Assessing the impact of symptoms

• This recommendation is based on the observation in the BSG guideline that the incidence of anxiety and depression is higher in people with inflammatory bowel disease than in control populations [Lamb 1, 2019], and is supported by expert opinion in review articles that inflammatory bowel disease can adversely affect psychosocial functioning [Rosen, 2015; Oliveira, 2017].
• The joint ECCO/ESPGHAN guideline recommends that psychological support should be available for children with a confirmed diagnosis of ulcerative colitis, as this may improve quality of life and wellbeing [Turner, 2018a].
• Expert opinion in a review article notes that symptoms such as fatigue, decreased energy levels, and reduced appetite should not be assumed to be secondary to inflammatory bowel disease, as they may reflect an underlying mood disorder [Oliveira, 2017].

Offering information and support

• The recommendation to offer information and support is based on the NICE clinical guideline on ulcerative colitis [NICE, 2019] and the BSG guideline [Lamb 1, 2019].
  • NICE states that advice and support for people with ulcerative colitis is important and should include information on the effects of the condition and its course, medical treatment options, the effects of drug treatment, and the monitoring required.
• The recommendation to encourage healthy lifestyle measures including regular exercise is based on the guideline on fatigue management [Kreijne, 2016] and the joint ECCO/ESPGHAN guideline [Turner, 2018a], which highlight potential benefits for fatigue management, growth, and bone health.

Assessing osteoporosis risk

• The recommendation to monitor bone health and assess osteoporosis risk is based on the NICE clinical guideline on ulcerative colitis [NICE, 2019], the BSG guideline [Lamb 1, 2019], the joint ECCO/ESPGHAN guideline [Turner, 2018a], and the BSPGHAN guideline [Sandhu, 2010].
  • The NICE guideline development group noted an increased risk of osteoporosis in people with ulcerative colitis compared with the general population, especially during disease relapse, with persistent disease, and when taking corticosteroids. It recommended monitoring bone health in children and young people with ulcerative colitis during chronic active disease, after recurrent active disease, and after treatment with oral corticosteroids.
  • In addition, potentially poor nutritional status due to reduced micronutrient intake and absorption may have a significant impact on bone status in children [Turner, 2018a].
  • The BSPGHAN guideline recommends ensuring an adequate intake of calcium and vitamin D, and considering supplementation if this is insufficient.

Ensuring specialist follow-up and surveillance

• The BSG guideline states that people with inflammatory bowel disease should be cared for by a defined multidisciplinary team including gastroenterologists, colorectal surgeons, nurse specialists, a dietitian, pharmacist, and gastrointestinal radiologist. This should allow for early initiation of appropriate therapy and ongoing assessment of disease progress and any adverse effects of treatment [Lamb 1, 2019].
• The recommendations on colonoscopic surveillance for colorectal cancer are based on the NICE guideline on colonoscopic surveillance [NICE, 2022a], the ECCO consensus guidelines on diagnosis and management [Magro, 2017] and malignancies [Annese, 2015], and expert opinion in review articles [Ford, 2013; Rosen, 2015].
  • The risk of colorectal cancer in people with ulcerative colitis is increased compared with the general population, and is particularly associated with increased disease duration, disease extent, and more severe or persistent inflammatory activity. In addition, a family history of colorectal cancer and the presence of co-morbid primary sclerosing cholangitis increases the risk further [Annese, 2015; Magro, 2017; NICE, 2022a].
  • Surveillance colonoscopy may allow earlier detection and potentially prevent progression to colorectal cancer, thereby improving prognosis [Magro, 2017; NICE, 2022a].
• The recommendations on monitoring a child or young person's growth and pubertal development are based on the NICE clinical guideline [NICE, 2019], the joint ECCO/ESPGHAN guideline [Turner, 2018a], and expert opinion in review articles [Rosen, 2015; Oliveira, 2017].
  • The NICE guideline development group noted that children and young people with ulcerative colitis are at risk of growth and pubertal delay, especially during relapse, persistent disease, when approaching puberty, and when taking corticosteroids. Monitoring growth and pubertal development by professionals with appropriate expertise is therefore recommended, as restricted growth or pubertal delay can impact on the child or young person's social and emotional development.
  • This approach is supported by expert opinion in a review article, which states that children with inflammatory bowel disease are at risk of macro- and micronutrient deficiencies, with weight loss occurring in 34% of children with ulcerative colitis. Delayed skeletal maturation and growth failure may sometimes lead to delayed puberty [Oliveira, 2017].
  • The joint ECCO/ESPGHAN guideline notes that growth impairment is rare in children with ulcerative colitis who are not corticosteroid-dependent.

Prescribing and monitoring drug treatments

• The recommendation on ensuring appropriate monitoring of drug treatments is based on the NICE clinical guideline on ulcerative colitis [NICE, 2019], the BSG guideline [Lamb 1, 2019], the joint ECCO/ESPGHAN guideline [Turner, 2018a] and expert opinion in a review article [Oliveira, 2017].
• The recommendation on monitoring for nutritional deficiencies is based on the ECCO consensus guidelines on diagnosis and management [Magro, 2017] and iron deficiency and anaemia [Dignass, 2015], the ESPEN guideline on nutrition [Bischoff, 2023], the joint ECCO/ESPGHAN guideline [Turner, 2018a], a guideline on fatigue management [Kreijne, 2016], and expert opinion in review articles [Fell, 2016; Oliveira, 2017].
  • The ECCO consensus guideline notes that anaemia is the most common systemic complication and extra-intestinal manifestation of inflammatory bowel disease, and recommends that all people with inflammatory bowel disease should be assessed for anaemia regularly because of its high prevalence and potential impact on quality of life. It also notes that recurrent anaemia may indicate persistent disease activity even if there is clinical remission and serum inflammatory markers are normal [Dignass, 2015].
  • People with inflammatory bowel disease are at increased risk of malnutrition and nutritional deficiencies due to gut loss from diarrhoea, chronic inflammation, and inadequate dietary intake due to reduced appetite accompanying disease activity, and people should be checked for nutritional deficiencies regularly [Kreijne, 2016; Bischoff, 2023]. In addition, 'backwash ileitis' is observed in up to 20% of people with extensive colitis which may affect small bowel nutrient absorption [Magro, 2017].
  • Expert opinion in a review article notes that recognition and treatment of iron deficiency and other nutritional deficits is important for the general wellbeing of children with ulcerative colitis [Fell, 2016].
  • The joint ECCO/ESPGHAN guideline notes that vitamin D should be supplemented in children if deficiency is identified, regardless of corticosteroid use [Turner, 2018a].

Assessing for clinical features of relapse or troublesome symptoms

• The recommendation on checking the person's body mass index (BMI) is extrapolated from the ESPEN guideline on nutrition, which states that as people with inflammatory bowel disease are at increased risk of malnutrition, they should be screened for this on a regular basis [Bischoff, 2023].
  • People with malnutrition have a worse prognosis, are more likely to be hospitalized, are at increased risk of infection and venous thromboembolism, and have increased mortality rates compared with people who are not malnourished. In addition, malnourished children are at increased risk of growth failure and delayed pubertal development.
  • Malnutrition may be the result of reduced oral intake, increased nutrient requirements, and increased gastrointestinal losses. People with ulcerative colitis are more at risk when the disease is active.
• The recommendation on checking serum inflammatory markers is based on the ECCO consensus guideline on management [Harbord, 2017], the joint ECCO/ESPGHAN guideline on acute severe disease [Turner, 2018], and expert opinion in a review article [Ford, 2013].

Arranging specialist referral

• The recommendation to arrange referral if there are suspected extra-intestinal manifestations is extrapolated from the BSG guideline [Lamb 1, 2019] and the ECCO consensus guideline on extra-intestinal manifestations [Harbord, 2016]. It is also pragmatic, based on what CKS considers to be good clinical practice.
  •  The ECCO consensus guideline notes that the management of complex extra-intestinal manifestations should be discussed in a multi-disciplinary team setting.
• The recommendations to arrange referral to a colorectal surgeon and/or stoma nurse have been extrapolated from the NICE clinical guideline [NICE, 2019]. They are also pragmatic, based on what CKS considers to be good clinical practice.
• The recommendation to consider referral to a dietitian is extrapolated from the ESPEN guideline, which states that nutritional care is important, particularly in children, to promote optimal growth and pubertal development [Bischoff, 2023].

Advice on vaccinations

• These recommendations are based on the BSG guideline [Lamb 1, 2019], the ECCO consensus guideline on diagnosis and management [Magro, 2017], and expert opinion in a review article [Ford, 2013].
  • People with ulcerative colitis may be at increased risk of opportunistic infections due to underlying disease activity, malnutrition, long-term immunosuppressive drug treatment, or surgery [Magro, 2017; Lamb 1, 2019].

Disease severity assessment tools

Table 1. Truelove and Witts' severity index for assessing severity of ulcerative colitis in adults.

Table 2. Paediatric Ulcerative Colitis Activity Index (PUCAI) for assessing severity of ulcerative colitis in children and young people.

Basis for recommendation

The recommendations on management of suspected acute severe disease are largely based on the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], the National Institute for Health and Care Excellence (NICE) clinical guideline Ulcerative Colitis: management [NICE, 2019], the European Crohn's and Colitis Organisation (ECCO) consensus guidelines Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders [Magro, 2017], Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management [Harbord, 2017] and Practical guideline for fatigue management in inflammatory bowel disease [Kreijne, 2016]; the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline Clinical nutrition in inflammatory bowel disease [Bischoff, 2023], two joint ECCO and European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) evidence-based guidelines Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care [Turner, 2018a] and Management of Paediatric Ulcerative Colitis, Part 2: Acute severe colitis [Turner, 2018], and expert opinion in review articles on ulcerative colitis [Ford, 2013; Fell, 2016] and inflammatory bowel disease in children [Rosen, 2015].

Clinical features of acute severe disease

• The information on clinical features suggesting acute severe disease are based on the BSG guideline [Lamb 1, 2019], the NICE clinical guideline [NICE, 2019], the ECCO consensus guideline on management [Harbord, 2017], the joint ECCO/ESPGHAN guidelines [Turner, 2018a; Turner, 2018], and expert opinion in review articles [Ford, 2013; Fell, 2016].
  • Use of a disease severity scoring tool may help to distinguish people with severe symptoms needing hospital admission from people with mild or moderately active disease who need outpatient clinic referral [Harbord, 2017; Lamb 1, 2019].
  • The ECCO consensus guideline on management notes that the Truelove and Witt severity index remains the best validated and most widely used scoring tool. Bloody diarrhoea is a key clinical feature, with one additional parameter needed to define a severe flare-up of disease [Harbord, 2017]. The body mass index (BMI) parameter is based on the ESPEN guideline on nutrition which states that this value reflects undernutrition and disease-associated catabolism [Bischoff, 2023]. CKS notes that raised inflammatory markers including C-reactive protein (CRP) in addition to erythrocyte sedimentation rate (ESR) cited in the Truelove and Witt severity index, may be used to help identify acute severe disease activity [Ford, 2013; Harbord, 2017; Magro, 2017; Turner, 2018].
  • The NICE clinical guideline and the ECCO/ESPGHAN guideline recommend using the Paediatric Ulcerative Colitis Activity Index (PUCAI) to monitor disease activity when children are reviewed [NICE, 2019; Turner, 2018a]. Repeat PUCAI scoring may be helpful in monitoring disease activity and response to treatment [Fell, 2016]. However, CKS notes that the retrospective recall of symptoms needed to complete a disease severity tool may not always be reliable, especially in children and young people.

Arranging urgent hospital admission

• People with acute severe colitis require emergency hospital admission because it may be life-threatening or they may require specialist hospital treatment for symptom control [Harbord, 2017; Magro, 2017; Turner, 2018; Lamb 1, 2019; NICE, 2019].
  • The ECCO consensus guideline on diagnosis and management notes that immediate hospital admission is needed for all people fulfilling criteria for severe colitis, to prevent delayed decision-making which may lead to increased peri-operative morbidity and mortality [Magro, 2017].
  • The joint ECCO/ESPGHAN guideline notes that, with few exceptions, children with acute severe colitis should be admitted to hospital for immediate evaluation and intensive medical treatment with intravenous corticosteroids to induce remission. In addition, alternative diagnoses such as toxic megacolon or bowel perforation should be excluded if there is severe or escalating abdominal pain [Turner, 2018].
  • This approach is supported by the NICE clinical guideline [NICE, 2019], the BSG guideline [Lamb 1, 2019], and expert opinion in a review article [Ford, 2013] that intravenous corticosteroids, rescue therapy with infliximab or ciclosporin, or early surgical intervention may be needed.

Management if admission not indicated

• The recommendation to exclude alternative causes for symptoms suggesting a disease flare-up such as checking for Clostridium difficile infection is based on the ECCO consensus guidelines [Harbord, 2017; Magro, 2017] and expert opinion in a review article [Fell, 2016].
  • Ulcerative colitis is an independent risk factor for infection with C. difficile [Magro, 2017].
  • The joint ECCO/ESPGHAN guideline on management notes that enteric infections and adverse effects of medications (primarily mesalazine and thiopurines) can mimic acute severe colitis and need to be excluded [Turner, 2018].
  • The ECCO consensus guideline on current management notes that causes of refractory disease include poor adherence to therapy, unrecognised complications, or an inappropriate diagnosis [Harbord, 2017]. 
• The recommendation to arrange an urgent gastroenterology review appointment or seek specialist advice is based on the ECCO consensus guideline on management [Harbord, 2017] and the BSG guideline, which states that people experiencing a possible relapse of inflammatory bowel disease should have access to specialist review within five working days [Lamb 1, 2019]. It is also extrapolated from expert opinion in a review article which states a person's specialist should be contacted in the event of a relapse of ulcerative colitis [Ford, 2013].
• The information on considering starting oral corticosteroids in primary care is extrapolated from the ECCO consensus guideline on management, which states that systemic corticosteroids are appropriate in people with moderate to severe disease activity and in those with mild activity who do not respond to oral mesalazine [Harbord, 2017].
• The recommendation that nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in acute severe colitis is based on the ECCO consensus guideline on diagnosis and management [Magro, 2017] and the joint ECCO/ESPGHAN guideline on management of acute severe colitis [Turner, 2018].
• The recommendation to consider referral to a dietitian is extrapolated from the ESPEN guideline, which states that nutritional care is important, particularly in children, to promote optimal growth and pubertal development [Bischoff, 2023].

Management of recurrent flares of disease activity

• The recommendation to seek specialist advice about recurrent disease flares is based on the NICE clinical guideline [NICE, 2019] and the joint ECCO/ESPGHAN guideline on management [Turner, 2018a], and is also extrapolated from the ECCO consensus guideline on current management [Harbord, 2017] and supported by expert opinion in the BSG guideline [Lamb 1, 2019] and in review articles [Ford, 2013; Rosen, 2015].
  • Elective colectomy surgery may be curative (with ileostomy or ileo-anal pouch) and this may be appropriate for unresponsive or frequently relapsing disease that is affecting the person's quality of life [Harbord, 2017; NICE, 2019]. The joint ECCO/ESPGHAN guideline notes that elective colectomy should be considered in children with active or corticosteroid-dependent ulcerative colitis despite optimized medical therapy [Turner, 2018a].
  • Surgical intervention may be indicated if disease is not responding to intensive medical therapy, if there is poorly controlled disease, or if there are recurrent flare-ups [Rosen, 2015; Lamb 1, 2019].

Basis for recommendation

The recommendations on the management of symptoms are largely based on the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], the National Institute for Health and Care Excellence (NICE) clinical guideline Ulcerative Colitis: management [NICE, 2019], the European Crohn's and Colitis Organisation (ECCO) consensus guidelines Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management [Harbord, 2017], European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases [Dignass, 2015], The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease [Harbord, 2016], and Practical guideline for fatigue management in inflammatory bowel disease [Kreijne, 2016]; the joint ECCO and European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) evidence-based guideline Management of Paediatric Ulcerative Colitis, Part 2: Acute severe colitis [Turner, 2018]; the British Society of Paediatric Gastroenterology, Hepatology, and Nutrition (BSPGHAN) consensus document Guidelines for the management of inflammatory bowel disease in children in the United Kingdom [Sandhu, 2010], the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline Clinical nutrition in inflammatory bowel disease [Bischoff, 2023], and expert opinion in review articles on ulcerative colitis [Collins, 2006] and on inflammatory bowel disease [Shah, 2007; Kefalakes, 2009; Oliveira, 2017].

Management of diarrhoea

• These recommendations are based on the BSG guideline [Lamb 1, 2019], the ESPEN guideline on nutrition [Bischoff, 2023], and expert opinion in a review article [Shah, 2007]. They are also pragmatic, based on what CKS considers to be good clinical practice.

Management of constipation

• The recommendation to increase the amount of soluble fibre in the diet is based on the ESPEN guideline on nutrition [Bischoff, 2023], and is pragmatic, based on what CKS considers to be good clinical practice.
• The recommendation to use bulk-forming laxatives is based on expert opinion in a review article which suggests that proximal constipation may be relieved by bulk-forming laxatives [Collins, 2006]. The British National Formulary (BNF) notes that some other types of laxative (including macrogols) are contraindicated for use in severe inflammatory bowel disease [BNF, 2024].

Management of abdominal pain

• The information that persistent or recurrent pain may indicate poor disease control is based on information in the BSG guideline [Lamb 1, 2019] and the BSPGHAN guideline [Sandhu, 2010].
• The recommendations to offer paracetamol and avoid nonsteroidal anti-inflammatory drugs (NSAIDs) which may exacerbate colitis symptoms are based on the BSG guideline [Lamb 1, 2019] and the joint ECCO/ESPGHAN guideline [Turner, 2018]. The information about the risks of NSAID use is supported by expert opinion in a review article [Kefalakes, 2009].
• The recommendation to avoid opiate analgesia is based on the fact it can affect bowel motility and lead to stasis and toxic megacolon [Turner, 2018; Lamb 1, 2019].

Management of fatigue

• These recommendations are based on the ECCO consensus guidelines on iron deficiency and anaemia [Dignass, 2015] and fatigue management [Kreijne, 2016], and the BSG guideline [Lamb 1, 2019]. They are also supported by the expert opinion of previous external reviewers of this CKS topic. 

  • The ECCO consensus guideline on fatigue management notes that inflammatory bowel disease-related fatigue is an underdiagnosed and undertreated issue in clinical practice with a severe negative effect on the person's quality of life. Many factors are known to contribute to fatigue, such as inflammation, pain, emotional distress, sleep disturbance, anaemia, alterations in nutrition and overall nutritional status, and reduced activity levels. In addition, adverse effects of medications and alcohol and/or drug misuse may be relevant [Kreijne, 2016].

  • The information on medications that may cause drug-induced anaemia is based on the BSG guideline [Lamb 1, 2019].

Management of oral problems

• This recommendation is based on the BSPGHAN guideline [Sandhu, 2010] and the BSG guideline [Lamb 1, 2019]. It is also pragmatic, based on what CKS considers to be good clinical practice.

Basis for recommendation

The recommendations on contraception, fertility, and pre-pregnancy planning are largely based on the European Crohn's and Colitis Organisation (ECCO) consensus guideline The second European evidence-based consensus on reproduction and pregnancy in inflammatory bowel disease [van der Woude, 2015], the College of Sexual and Reproductive Healthcare (CoSRH) guidelines Sexual and reproductive health for individuals with inflammatory bowel disease [CoSRH, 2016] and UK Medical Eligibility Criteria for Contraceptive Use (UKMEC 2019) [CoSRH, 2019], the British Society of Gastroenterology (BSG) Guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], and expert opinion in a review article on ulcerative colitis [Ford, 2013].

Advice on contraception issues

• The information on factors affecting the choice of contraceptive method, and the safety and efficacy of oral methods, is based on the CoSRH UKMEC document [CoSRH, 2019].
• The recommendations on the use of effective contraception during and after taking certain specialist drug treatments are based on the CoSRH guideline on inflammatory bowel disease (IBD) [CoSRH, 2016] as well as advice from the drug manufacturers [EMC, 2021; EMC, 2023a; EMC, 2023b; EMC, 2024]. The basis for the recommendations to avoid pregnancy while taking these drugs include:
  • High-dose methotrexate used in the management of ectopic pregnancy is an abortifacient and can cause congenital malformation when used in the first trimester. Data on the lower doses used to treat ulcerative colitis are equivocal regarding risk of fetal harm but the drug should be avoided in pregnancy as a precaution  [UKTIS, 2022a].
  • Methotrexate use in males poses a theoretical risk of sperm damage. The limited available data do not suggest adverse effects on pregnancy outcomes where the male partner used methotrexate around the time of conception. However, as a precaution, some men may be offered an alternative treatment if planning to father a pregnancy. The recommendation for males to avoid methotrexate for 6 months prior to conception is to allow for several methotrexate-free sperm cycles  [UKTIS, 2020]. 
  • Preclinical (animal) data suggests that mercaptopurine has teratogenic potential. The available human data, which mainly relate to the use of the pro-drug azathioprine, are reassuring [UKTIS, 2024]. The BSG recommends that thiopurines can be used in pregnancy [Lamb 1, 2019] and CKS notes that in practice, azathioprine is commonly used in pregnancy to treat inflammatory conditions.
  • While the manufacturers of infliximab and adalimumab advise that these drugs should be avoided during pregnancy where possible, there is no evidence of fetal harm and the BSG [Lamb 1, 2019] and UK Teratology Information Service (UKTIS) [UKTIS, 2022b; UKTIS, 2022c] advise that they can be continued where there are clear benefits of treatment, especially as uncontrolled UC is associated with adverse pregnancy outcomes.

Advice on fertility issues

• A population-based cohort study (n=11,163 women with UC) found that histologic inflammation was associated with a statistically significant reduction in fertility, corresponding to an approximately 10% decreased fertility rate compared to matched women in the background population. Clinically apparent UC activity was associated with approximately 16% reduced fertility [Mårild, 2024].
• The information on the potential impact of pelvic or abdominal sepsis or surgery on fertility is based on the ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015] and the CoSRH guideline on IBD [CoSRH, 2016].
  • The CoSRH guideline notes that for women following pelvic surgery, such as a proctocolectomy or an ileal pouch-anal anastomosis (IPAA), the risk of subfertility may increase as much as three-fold.
• The information on the effects of sulfasalazine, methotrexate, and infliximab on male spermatogenesis and semen motility is based on the ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015] and the CoSRH guideline on IBD [CoSRH, 2016].

Advice on pre-pregnancy planning

• The ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015], the CoSRH guideline on IBD [CoSRH, 2016], and the BSG guideline [Lamb 1, 2019] recommend referral for pre-conception counselling for men and women with inflammatory bowel disease, to advise and optimize disease management before conception.
  • Optimum disease control is needed prior to conception and during pregnancy, as if conception occurs during active ulcerative colitis, there is an increased risk of persistent disease activity or relapse during pregnancy, and an increased risk of adverse pregnancy outcomes, such as miscarriage, preterm labour, and low birth-weight [Ford, 2013; van der Woude, 2015; Lamb 1, 2019]. If conception occurs at a time of quiescent disease, the risk of relapse is the same as in non-pregnant women [van der Woude, 2015].
  • The rate of voluntary childlessness is higher among women with ulcerative colitis than the general population. This may be due to concerns about the risk of adverse pregnancy outcomes, possible teratogenicity of drug treatments, and the heritability of the disease. Pre-pregnancy counselling may provide an opportunity for women to identify and discuss these issues [van der Woude, 2015; CoSRH, 2016].
• The CoSRH guideline on IBD notes that the decision to discontinue any treatment requires expert clinical judgement, balancing the risks of stopping the drug against the risks associated with continuing [CoSRH, 2016].

Basis for recommendation

The recommendations on pregnancy and breastfeeding are largely based on the National Institute for Health and Care Excellence (NICE) clinical guideline Ulcerative Colitis: management [NICE, 2019], the European Crohn's and Colitis Organisation (ECCO) consensus guideline The second European evidence-based consensus on reproduction and pregnancy in inflammatory bowel disease [van der Woude, 2015], the College of Sexual and Reproductive Healthcare (CoSRH) guideline Sexual and reproductive health for individuals with inflammatory bowel disease [CoSRH, 2016], the British Society of Gastroenterology (BSG) Guidelines on the management of inflammatory bowel disease in adults [Lamb 1, 2019], and expert opinion in a review article on ulcerative colitis [Ford, 2013].

Advice on pregnancy issues

• The recommendation that pregnant women are jointly managed by a gastroenterologist and obstetrician is based on the NICE clinical guideline [NICE, 2019], the CoSRH guideline on inflammatory bowel disease (IBD) [CoSRH, 2016], and the BSG guideline [Lamb 1, 2019]. It is also extrapolated from the ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015].
  • The NICE clinical guideline recommends effective communication and information-sharing across specialities, including obstetrics and gynaecology, gastroenterology, and primary care. This involves giving specialist information on the risks and benefits of drug treatments to induce or maintain remission during pregnancy.
  • Optimum disease control is needed during pregnancy, as persistent disease activity or relapse during pregnancy may be associated with an increased risk of adverse pregnancy outcomes, such as miscarriage, preterm labour, and low birth-weight [van der Woude, 2015; Lamb 1, 2019]. The CoSRH guideline on IBD notes that the benefits of clinical remission in pregnancy generally outweigh the risks to the fetus from specialist medication [CoSRH, 2016]. This is supported by expert opinion in a review article [Ford, 2013].
• The recommendation to seek immediate specialist advice if a woman or her partner is taking potentially teratogenic medication is based on the FSRH guideline on IBD, which notes that the decision to discontinue any treatment requires expert clinical judgement, balancing the risks of stopping the drug against the risks associated with continuing [CoSRH, 2016].
  • High-dose methotrexate used in the management of ectopic pregnancy is an abortifacient and can cause congenital malformation when used in the first trimester. Data on the lower doses used to treat ulcerative colitis are equivocal regarding risk of fetal harm but the drug is usually avoided in pregnancy as a precaution  [UKTIS, 2022a].
  • Methotrexate use in males poses a theoretical risk of sperm damage. The limited available data do not suggest adverse effects on pregnancy outcomes where the male partner used methotrexate around the time of conception. However, as a precaution, some men may be offered an alternative treatment if planning to father a pregnancy [UKTIS, 2020]. 
  • Preclinical (animal) data suggests that mercaptopurine has teratogenic potential. The limited human data, which mainly relates to the use of the pro-drug azathioprine are reassuring [UKTIS, 2024]. The BSG recommends that thiopurines can be used in pregnancy [Lamb 1, 2019] and CKS note that in practice, azathioprine is commonly used in pregnancy to treat inflammatory conditions.
  • The manufacturers of infliximab and adalimumab advise that these drugs should be avoided during pregnancy where possible . However, there is no evidence of fetal harm and the BSG [Lamb 1, 2019] and the UK Teratology Information Service (UKTIS) [UKTIS, 2022b; UKTIS, 2022c] advise that they can be continued where there are clear benefits of treatment, especially as uncontrolled UC is associated with adverse pregnancy outcomes. It is usually recommended that the administration of live vaccines in infants who were exposed in utero to adalimumab or infliximab is delayed for several months after birth [Lamb 1, 2019].
• The ECCO consensus guideline notes that adherence to planned maintenance treatment will reduce the risk of relapse in pregnancy [van der Woude, 2015].
• The information that a woman may be offered an elective Caesarean section in certain clinical situations is based on the CoSRH guideline on IBD [CoSRH, 2016], the ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015], and the BSG guideline [Lamb 1, 2019].

Advice on breastfeeding issues

• The recommendations on breastfeeding are based on the CoSRH guideline on IBD [CoSRH, 2016], the ECCO consensus guideline on reproduction and pregnancy [van der Woude, 2015], and are pragmatic, based on what CKS considers to be good clinical practice. 

  • The decision to discontinue any treatment requires expert clinical judgement, balancing the risks of stopping the drug against any risks associated with continuing [CoSRH, 2016].
  • The ECCO consensus guideline notes that in women with ulcerative colitis, the risk of a post-partum flare may be increased.