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Ulcerative Colitis

Ulcerative Colitis ( UC ) is a chronic, relapsing and remitting inflammatory disease of the colon with characteristic symptoms including bloody stools , diarrhoea , urgency , incontinence , fatigue , mucus discharge , cramps . night time bowel movements and an increased frequency in bowel movements ( Ungaro et al Lancet 2017 )

 

Part of conditions known as Inflammatory bowel disease ( IBD – Ulcerative Colitis and Crohn’s disease ) a group of chronic idiopathic inflammatory diseases of the gastrointestinal tract with symptoms evolving in a relapsing and remitting manner The prevalence of IBD has increased worldwide over the last 50 yrs Highest prevalence of UC has been noticed in Europe and N America – although rate of IBD is rising in the developing world ( possibly related to improved hygiene and sanitation which has led to reduced exposure to enteric infections and immaturity of the immune systems ) Incidence and prevalence of UC varies geographically It can be said that IBD is closely linked to a westernized environment and lifestyle In the developed world UC has plateaued or has even reduced UC is more common than CD ( Crohn’s disease ) in adults Often presents in young adulthood – peak incidence is reported in 2nd to 4th decade of life ( a second modest rise is also noted in later life- ie a bimodal pattern of incidence Mortality from UC has reduced possibly due to a combination of use of steroids ,sulfasalazine and optimization in surgical techniques NICE reports a prevalence of 243 per 10,000 which amounts to 146,000 patients with UC in UK UC is uncommon in children – although an increase in incidence in the paediatric / adolescent population has been noticed

 

Diffuse , continuous and superficial inflammation of the rectal and colonic mucosa UC involves the rectum in 95 % of cases and can extend continuously and circumferentially to more proximal parts of the large intestine ( ie the disease tends to begin in the rectum and then extends ) Defects in the epithelial barrier , immune response , leukocyte recruitment and microflora of the colon Inflammation leads to small ulcers on the lining of the large intestine which can cause bleeding , pus , diarrhoea , abdominal pain / cramping , nausea and extreme fatigue Histologically – it is known that in UC inflammation is limited to the mucosa whereas in CD it is transmural and histological features are so called granulomas Pathogenesis is complex ( still evolving ) and can be summarised as ‘ development of inadequate immune response to the intestinal microbial flora , which appears in a genetically susceptible individual ‘

 

Etiology of IBD is thought to be multifactorial ; both genetic and environmental factors contribute to development Smoking is the most consistent and established risk factor – it increases the risk of CD while conferring protection against UC
- smokers have milder disease and fewer hospitalization
- they need less medications
- smoking cessation increases the risk of UC development No other modifiable well established harmful or protective factor has been identified Family history reported as the most important independent risk factor 
- a 1st degree relative with UC increases the risk of UC by 4 times
- Jewish ethnicity increases the risk Appendicectomy – reduces the risk of UC ( particularly if done before age 20 ) Vitamin D C Diff and other enteric infections Use of antibiotics and NSAIDs ( disruption of microbiome and intestinal barrier ) Depression , stress , sleep and neurobehavioural factors Diet Hormones

 

UC is a lifelong condition It is associated with significant morbidity and the potential for social and psychological sequelae particularly if untreated or poorly controlled Relapses and severe flare ups are common
- during an episode of severe UC 20% will need colectomy on their 1st admission and 40 % on their 2nd admission
- mortality from acute severe colitis is p to 2 % It has also been reported that UC patients with C.diff have a higher morbidity and mortality than patients with just UC ( Frank Senatore et al 2019 ) UC has a known association with the development of colorectal cancer with greatest risk in long standing and extensive disease Problems / complications following surgery as stoma care , ileoanal pouch use , urgency , leakage , soiling , fertility issues The global burden of UC continues to rise , along with the associated healthcare and societal costs

 

An illness which manifests in young people with main symptoms of mucous and bloody diarrhoea with or without abdominal pain. Based on the extent and severity of the disease the presentation may vary for e.g

Proctitis –intense mucorrhoea tenesmus faecal incontinence defecation urgency vomiting fever anorexia bloating abdominal distension

 

Ask about stool frequency , consistency blood and mucus
- diarrhoea is often preceded by abdominal cramps which get better with defecation
- it can happen during the day or the night Abdominal pain -is generally mild to moderate but can be severe if complications as fulminant colitis and toxic megacolon is present Weight loss Family history Extraintestinal manifestations EIMs ( e.g joint , dermatological , ophthalmological , hepatobiliary and haematological ) Extraintestinal manifestations may happen before or after the intestinal event and they are seen in 25 % to 40 % of IBD patients

 

Symptoms of proctitis as above but the disease can involve the left semicolon ( left colitis ) or often extend throughout the colon ( pancolitis ) and the symptoms / presentation will vary accordingly. The symptoms will not necessarily be always proportional to the extent of the disease .

 

Extraintestinal manifestations can happen with both CD and UC. Musculoskeletal and dermatological are more common although they may involve any organ system
 MSK- arthritis , colitic type , ankylosing spondylitis , sacroiliitis Dermatological – erythema nodosum ,pyoderma gangrenosum , aphthous ulcers Scleritis , episcleritis and uveitis Primary sclerosing cholangitis

 

Diagnosis is established using a combination of History and clinical examination Laboratory tests Radiological and endoscopic findings Histology

 

FBC and routine biochemical profile Serum CRP and ESR Serological markers as pANCA and ASCA- anti-Saccharomyces antibody
( it is now known that about 65 % of patients with UC have + ve perinuclear antineutrophil cyto plasmatic antibodies & these patients tend to have more severe disease ) Faecal calprotectin ( has good sensitivity to diagnose bowel inflammation although little specificity ) Plain abdominal XR / Barium enema / US Stool culture for Clostridium difficile ( also obtain stool sample in all cases of disease flare up )

 

UC is a chronic lifelong disease Endoscopy must be done at some point with biopsy During the initial presentation a conclusive diagnosis may be difficult to establish and about 40 % of those who are considered to have IBD unclassified ( indeterminate colitis ) may later found to have UC .

Conversely about 5 % initially thought to have UC will be diagnosed with CD
 The disease is characterized by periods of relapse with debilitating symptoms and remission -up to 90 % will have one or more relapses after the 1st attack Several criteria exist to define the extent and severity of the disease

 

E-1 proctitis- limited to rectum E2 -affects the rectum and left colon -distal to the the splenic flexure E3 affects the rectum and colon proximal to the splenic flexure.

 

This the Montreal classification which takes into consideration that the UC mostly involves the distal segments of the large bowel and classifies the disease into 3 groups. NICE has used the Truelove and Witts severity index to categorize disease severity into mild ,moderate and severe You may use calculators available online for eg on MD CALC to determine the disease severity or look at the handy UC flare pathway management chart from the IBD toolkit.

 

Main goal of treatment is clinical remission of active disease remission maintenance without corticosteroids prevention of complications improvement of QoL

 

5 ASA preparations-shown to induce remission in mild to moderate disease- first line drugs usually well tolerated best evidence for mesalazine ( also better tolerated than sulfasalazine ) come in different forms ( oral , suppository , liquid enema ) may take up to 8 weeks to achieve remission suppositories or retention enema- use of preparation PR is considered topical ( often first line treatment ) main SEs are headache , abdominal pain , nausea , vomiting , skin rash and diarrhoea monitor for nephrotoxicity combination therapy ( oral+ topical ) is recommended in extensive disease how they work is not entirely clear- developed as antibacterial & and anti-inflammatory agents

 

Corticosteroids -indicated in patients with mild or moderate UC in whom 5-ASA therapy has failed or not tolerated useful in controlling acute attacks not indicated for remission maintenance and courses of oral corticosteroids should be time limited ( usually 4-8 weeks ) oral prednisolone is the most common preparation see the UC flare up pathway for details how to issue beware of SEs which can include infections , weight gain , hyperglycaemia , acne , hirsutism , hypertension and osteoporosis

 

Others -Refractory cases will be managed by hospital specialists using options as biologics , surgery ,immunomodulators

 

Please refer to UC flare up pathway which has been developed by RCGP / Crohns Colitis foundation -a very useful tool. Other than managing the acute flare up its also important to pay attention on the following aspects of care.

 

Increased risk- colorectal cancer

EIM-bone health ( osteoporosis and osteopenia ) opportunistic infections increased risk thromboembolism ^ ed risk primary sclerosing cholangitis

Psychological health anxiety and depression

Vaccination -Patients may be immunosuppressed – ensure vaccination ( non-live ) as per local guidelines

Side effects of medications -loss of BMD due to steroids interstitial nephritis is a serious complication of 5-ASA treatment

Pregnancy-patients often young and the disease has serious implication on pregnancy

Complications from surgery -most commonly performed procedure for medically refractive UC is restorative proctocolectomy 
( RPC ) with ileal pouch anal anastomosis ( complications can happen for e.g leak from anastomosis , fistulas , etc )

PATIENT INFORMATION

Crohn’s and Colitis UK -A comprehensive resource -every patient should be aware of this  https://www.crohnsandcolitis.org.uk/about-crohns-and-colitis/publications/ulcerative-colitis

Another wonderful resource from US Crohn’s and Colitis Foundation https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/overview

Canadian Society of Intestinal Research on UC https://badgut.org/information-centre/a-z-digestive-topics/ulcerative-colitis/

A good resource from – Guts charity UK https://gutscharity.org.uk/advice-and-information/conditions/ulcerative-colitis/

Printable information from The Association of Colproctology of Great Britain and Ireland https://www.acpgbi.org.uk/patients/conditions/ulcerative-colitis/

 

References

  1. Abdulrazeg OmniaLi BernadetteEpstein JennyManagement of ulcerative colitis: summary of updated NICE guidance 
  2. Davis, Stephanie C. PhD, RN, FNP-BC; Robinson, Brittani L. MS, RN, FNP-C; Vess, Joy DNP, RN, ACNP-BC; Lebel, Joseph S. MD Primary care management of ulcerative colitis, The Nurse Practitioner: January 15, 2018 – Volume 43 – Issue 1 – p 11-19 doi: 10.1097/01.NPR.0000527565.05934.14
  3. Levine, Jonathan S, and Robert Burakoff. “Extraintestinal manifestations of inflammatory bowel disease.” Gastroenterology & hepatology vol. 7,4 (2011): 235-41.Extraintestinal Manifestations of Inflammatory Bowel Disease (nih.gov)
  4. Collins, Paul, and Jonathan Rhodes. “Ulcerative colitis: diagnosis and management.” BMJ (Clinical research ed.) vol. 333,7563 (2006): 340-3. doi:10.1136/bmj.333.7563.340
  5. Lamb CAKennedy NARaine T, et al
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    Volume 35, Issue 4,
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  7. Ulcerative Colitis: Current and Emerging Treatment
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    Maia Kayal 1 and Shailja Shah 2 J. Clin. Med. 2020, 9, 94; doi:10.3390/jcm9010094
  8. Qiu, Y., Chen, B., Li, Y. et al. Risk factors and long-term outcome of disease extent progression in Asian patients with ulcerative colitis: a retrospective cohort study. BMC Gastroenterol 19, 7 (2019). https://doi.org/10.1186/s12876-018-0928-2
  9. Environmental Risk Factors for Inflammatory Bowel Disease Ashwin N. Ananthakrishnan, MD, MPH Gastroenterology & Hepatology Environmental Risk Factors for Inflammatory Bowel Disease – Gastroenterology & Hepatology (gastroenterologyandhepatology.net)

  10. Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses Daniele Piovani Silvio Danese Laurent Peyrin-Biroulet Georgios K. Nikolopoulos Theodore Lytras Stefanos Bonovas ALIMENTARY TRACT| VOLUME 157, ISSUE 3

  11. ULCERATIVE COLITIS
    Author: Dr Sandro Ardizzone1 Creation date: September 2003
    Scientific Editor: Prof Gabriele Bianchi Porr *Titre (orpha.net)
  12. Risk factors for complications in patients
    with ulcerative colitis Christine N Manser1,2, Jan Borovicka3
    , Frank Seibold4 , Stephan R Vavricka1,5, Peter L Lakatos6
    , Michael Fried1 and Gerhard Rogler1 ; the investigators
    of the Swiss Inflammatory Bowel Disease Cohort Study Risk factors for complications in patients
    with ulcerative colitis United European Gastroenterology Journal
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  13. Lynch WD, Hsu R. Ulcerative Colitis. [Updated 2020 Jun 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459282/
  14. da Silva, Bruno César et al. “Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis.” World journal of gastroenterology vol. 20,28 (2014): 9458-67. doi:10.3748/wjg.v20.i28.9458
  15. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 The Lancet Gastroenterology and Hepatology ARTICLES| VOLUME 5, ISSUE 1P17-30, JANUARY 01, 2020

  16. Pasvol TJHorsfall LBloom S, et al
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  17. Epidemiology, demographic characteristics and prognostic
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    Bruno César da Silva, Andre Castro Lyra, Raquel Rocha, Genoile Oliveira Santana World J Gastroenterol 2014 July 28; 20(28): 9458-9467
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  18. Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Similarities, Differences
    and a Lot of Things We Do Not Know Yet
    Anita Annaházi#
    and Tamás Molnár*# Molnar and Annaházi, J Clin Cell Immunol 2014,
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    DOI: 10.4172/2155-9899.1000253
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    Toshifumi HIBI
    Professor of Medicine, Department of Internal Medicine,
    Keio University School of Medicine Journal of the Japan Medical Association (Vol. 125, No. 2, 2001, pages 161–165) JMAJ, June 2003—Vol. 46, No. 6
  20. Ulcerative colitis
    Alexander C Ford,1 2 Paul Moayyedi,3
    Steven B Hanauer4 : BMJ 2013;346:f432
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