Inflammatory bowel disease (IBD) classically presents with bloody diarrhoea with rectal urgency and tenesmus. Typically the onset is gradual with progression over weeks but it can be acute.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
[24]Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet. 2023 Aug 12;402(10401):571-84.
http://www.ncbi.nlm.nih.gov/pubmed/37573077?tool=bestpractice.com
Rectal bleeding is reported by more than 90% of patients so it should be an important consideration in patients who have bloody diarrhoea and/or diarrhoea with signs of systemic inflammation.[25]Gros B, Kaplan GG. Ulcerative colitis in adults: a review. JAMA. 2023 Sep 12;330(10):951-65.
http://www.ncbi.nlm.nih.gov/pubmed/37698559?tool=bestpractice.com
Diagnosis requires, at a minimum, negative stool culture and some form of sigmoidoscopy or colonoscopy.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
History and examination
In addition to the presence of bloody diarrhoea, further suggestive features include:[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
a history of lower abdominal pain
faecal urgency
tenesmus (a feeling of needing to pass a stool even though the colon is empty), and
the presence of extraintestinal manifestations, particularly those related to disease activity, such as erythema nodosum and acute arthropathy.
UC should be suspected in patients with primary sclerosing cholangitis, as up to 70% have underlying inflammatory bowel disease.[26]Palmela C, Peerani F, Castaneda D, et al. Inflammatory bowel disease and primary sclerosing cholangitis: a review of the phenotype and associated specific features. Gut Liver. 2018 Jan 15;12(1):17-29.
http://www.gutnliver.org/journal/view.html?doi=10.5009/gnl16510
http://www.ncbi.nlm.nih.gov/pubmed/28376583?tool=bestpractice.com
Initial work-up
The initial work-up for all patients should include basic laboratory tests (full blood count [FBC], metabolic panel, inflammatory markers), stool studies, and either a colonoscopy or flexible sigmoidoscopy to visualise the mucosa and obtain a biopsy.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
An abdominal x-ray is ordered when initial presentation or subsequent relapses are associated with signs and symptoms of an acute abdomen.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
If there is uncertainty about the type of inflammatory bowel disease, an upper gastrointestinal work-up should be carried out to assess for Crohn’s disease present in the upper gastrointestinal tract.[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
Stool studies
Between 5% and 47% of cases of newly diagnosed or relapsing inflammatory bowel disease are associated with Clostridium difficile infection.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
Stool studies should be obtained, including comprehensive culture and C difficile toxin A and B immunoassay, even in patients with a relapse of known UC.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
White blood cells may be present in the stool with negative stool culture.
Faecal calprotectin (FC) testing
FC can be used in patients with UC as a non-invasive marker of disease activity and to assess response to therapy and relapse.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com
In the UK, FC testing is recommended in patients <60 years old to exclude inflammatory causes for recent onset lower gastrointestinal symptoms.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
[28]National Institute for Health and Care Excellence. Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. Oct 2013 [internet publication].
https://www.nice.org.uk/guidance/dg11
[29]Deputy M, Devanaboina R, Al Bakir I, et al. The role of faecal calprotectin in the diagnosis of inflammatory bowel disease. BMJ. 2023 Feb 13;380:e068947. It is elevated when there is bowel inflammation and correlates with endoscopic and histological gradings of disease severity.
FC testing is useful in supporting clinicians when considering inflammatory bowel disease in the differential diagnosis of irritable bowel syndrome. It can help determine which patients require urgent endoscopy and can prevent unnecessary referrals for colonoscopy (>60% in younger patients presenting with lower gastrointestinal symptoms, the majority of whom will not have inflammatory bowel disease).[28]National Institute for Health and Care Excellence. Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. Oct 2013 [internet publication].
https://www.nice.org.uk/guidance/dg11
In those with an established diagnosis of IBD this test can be useful to assess for ongoing bowel inflammation.[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
[28]National Institute for Health and Care Excellence. Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. Oct 2013 [internet publication].
https://www.nice.org.uk/guidance/dg11
[29]Deputy M, Devanaboina R, Al Bakir I, et al. The role of faecal calprotectin in the diagnosis of inflammatory bowel disease. BMJ. 2023 Feb 13;380:e068947.[30]Poullis A, Foster R, Northfield TC, et al. Review article: faecal markers in the assessment of activity in inflammatory bowel disease. Aliment Pharmacol Ther. 2002 Apr;16(4):675-81.
https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2036.2002.01196.x
http://www.ncbi.nlm.nih.gov/pubmed/11929384?tool=bestpractice.com
Laboratory studies
FBC may show leukocytosis, thrombocytosis, and anaemia.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
Inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) may be raised.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
[31]Croft A, Lord A, Radford-Smith G. Markers of systemic inflammation in acute attacks of ulcerative colitis: what level of C-reactive protein constitutes severe colitis? J Crohns Colitis. 2022 Aug 4;16(7):1089-96.
https://academic.oup.com/ecco-jcc/article/16/7/1089/6527048
http://www.ncbi.nlm.nih.gov/pubmed/35147694?tool=bestpractice.com
Metabolic abnormalities can include hypokalaemic metabolic acidosis secondary to diarrhoea; elevated sodium and urea secondary to dehydration; elevated alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase in patients with concomitant primary sclerosing cholangitis; and hypoalbuminaemia secondary to malnourishment or as an acute-phase reactant.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
Sigmoidoscopy and biopsy
Flexible sigmoidoscopy can be performed in the endoscopy unit without sedation or full bowel prep but can only visualise the distal colon. Full bowel prep and colonoscopy is required if disease is suspected to extend beyond the distal bowel on the basis of x-ray. Endoscopic evaluation with histological confirmation is the key to diagnosis, but histological features overlap considerably between UC, Crohn's disease, and infectious colitis; hence, the diagnosis is based on the combination of history, endoscopic findings, histology, and microbiology, rather than on any single modality.[7]World Gastroenterology Organisation. Global guidelines: inflammatory bowel disease. Aug 2015 [internet publication].
http://www.worldgastroenterology.org/guidelines/global-guidelines/inflammatory-bowel-disease-ibd/inflammatory-bowel-disease-ibd-english
During acute flares endoscopic examination should be limited to flexible sigmoidoscopy without bowel prep, due to the increased risk of perforation.
For a reliable diagnosis of IBD, ileocolonoscopy should be performed. A minimum of two biopsies from at least five sites along the colon, including the rectum and terminal ileum, should be obtained.[32]Magro F, Langner C, Driessen A, et al; European Crohn's and Colitis Organisation; European Society of Pathology. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013 Nov;7(10):827-51.
https://academic.oup.com/ecco-jcc/article/7/10/827/379239
http://www.ncbi.nlm.nih.gov/pubmed/23870728?tool=bestpractice.com
[33]Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019 Dec;68(suppl 3):s1-106.
https://gut.bmj.com/content/68/Suppl_3/s1.long
http://www.ncbi.nlm.nih.gov/pubmed/31562236?tool=bestpractice.com
[34]Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011 May;60(5):571-607.
http://www.ncbi.nlm.nih.gov/pubmed/21464096?tool=bestpractice.com
Imaging
Although generally reserved for those with severe or extensive colitis, plain abdominal radiography can help to rule out toxic megacolon or perforation at first presentation or during subsequent acute relapses.[27]Maaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019 Feb 1;13(2):144-64.
https://academic.oup.com/ecco-jcc/article/13/2/144/5078195
http://www.ncbi.nlm.nih.gov/pubmed/30137275?tool=bestpractice.com
The use of intestinal ultrasound has grown in recent years as a tool for objectively assessing and monitoring IBD activity including in UC. It is a non-invasive, radiation-free alternative to endoscopies and biomarkers which enables real-time, high-resolution examination of the bowel wall, mesentery, and adjacent structures.[35]Chavannes M, Dolinger MT, Cohen-Mekelburg S, et al. AGA clinical practice update on the role of intestinal ultrasound in inflammatory bowel disease: commentary. Clin Gastroenterol Hepatol. 2024 Sep;22(9):1790-95.e1.
https://www.cghjournal.org/article/S1542-3565(24)00454-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39001773?tool=bestpractice.com
The American Gastroenterology Association (AGA) suggests that it could be used as a screening tool in a similar way to FC, to rule out IBD, or to monitor disease activity.[35]Chavannes M, Dolinger MT, Cohen-Mekelburg S, et al. AGA clinical practice update on the role of intestinal ultrasound in inflammatory bowel disease: commentary. Clin Gastroenterol Hepatol. 2024 Sep;22(9):1790-95.e1.
https://www.cghjournal.org/article/S1542-3565(24)00454-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39001773?tool=bestpractice.com
Follow-up tests
Colonoscopy requires full bowel preparation and sedation. It is needed to assess the extent of disease if sigmoidoscopy suggests proximal extension. It is also indicated in patients with UC who are not responding well to treatment, in order to rule out infections (particularly cytomegalovirus and C difficile) and assess the need for surgery.[36]Shergill AK, Lightdale JR, Bruining DH, et al; American Society for Gastrointestinal Endoscopy Standards of Practice Committee. The role of endoscopy in inflammatory bowel disease. Gastrointest Endosc. 2015 May;81(5):1101-21;e13.
https://www.giejournal.org/article/S0016-5107(14)02386-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25800660?tool=bestpractice.com
Colonoscopy is also essential for cancer screening in long-standing cases.
Contrast computed tomography should be ordered when complications (e.g., primary sclerosing cholangitis) or other diagnoses are being considered.[23]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019 Mar;114(3):384-413.
http://www.ncbi.nlm.nih.gov/pubmed/30840605?tool=bestpractice.com