Ulcerative Colitis, Colon



Ulcerative Colitis, Colon


Scott R. Owens, MD





Key Facts


Terminology



  • Chronic, idiopathic, remitting, and relapsing inflammatory disease


  • Part of spectrum of inflammatory bowel disease (IBD)


Clinical Issues



  • Rectum usually involved



    • Variable amount of contiguous disease proximal to rectum


  • Correlation of histological and endoscopic findings essential for accurate diagnosis



    • Precise endoscopic appearance of any “polyps” or areas of raised mucosa important


    • Classically characterized by periods of remission and relapse (“UC flares”)


    • Markedly ↑ risk of dysplasia/neoplasia in IBD (1-2% ↑ carcinoma risk each year after 10 years)


Microscopic Pathology



  • Lymphoplasmacytic inflammation in lamina propria


  • Active inflammation


  • Evidence of chronic and ongoing mucosal injury


Diagnostic Checklist



  • Not all polypoid dysplasia in UC is DALM



    • Sporadic adenomas possible


  • Mucosal granulomas not specific to CD


  • Distribution of chronic changes most important in determination of type and overall extent of disease


Reporting Considerations



  • Knowledge of extent of disease important for ongoing assessment of colitis-associated dysplasia


  • Avoid phrases such as “nonspecific chronic colitis” or “nonspecific chronic inflammation”







Gross photograph shows a resected colon with active ulcerative colitis. Note erythema and granularity of mucosa image, as well as adherent mucopurulent exudate image.






Hematoxylin & eosin shows combined acute and chronic inflammation, characteristic of ulcerative colitis. A crypt abscess image is visible, as is intense lamina propria chronic inflammation image.


TERMINOLOGY


Abbreviations



  • Ulcerative colitis (UC)


Definitions



  • Chronic, idiopathic, remitting, and relapsing inflammatory disease



    • Autoimmune-like


    • Primarily affects colonic mucosa


    • Part of spectrum of inflammatory bowel disease (IBD)



      • Crohn disease (CD) → separate subtype of IBD


    • Associated with ↑ risk of neoplasia


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • UC may involve dysregulation of immune response to luminal bacteria



    • Response to infection and tolerance of commensal organisms normally closely controlled


    • Loss of normal regulation probably involves genetically determined susceptibility


Genetic Predisposition



  • Certain HLA haplotypes associated with UC



    • A7, A11


    • DRB*12, DRB*103


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Around 10-20/100,000 individuals in North America



      • Incidence reportedly increased in last 2 decades in USA and Europe


  • Age



    • Mean age at diagnosis in early 4th decade


    • 3 peaks of incidence



      • 1st in early 20s


      • 2nd in early 40s


      • 3rd in early 60s


  • Gender



    • M < F


    • Occurs earlier in women than in men


  • Ethnicity



    • Highest incidence in those of European descent


Site



  • UC classically involves only colon



    • Rectum usually involved



      • Can be termed ulcerative proctitis if limited to rectum


    • Variable amount of contiguous disease proximal to rectum



      • Proctosigmoiditis involves sigmoid colon and rectum


      • Left-sided UC begins in vicinity of splenic flexure and continues distally


      • Pancolitis begins proximal to hepatic flexure and continues distally


    • Appendix may be involved


    • Relatively rare upper tract (particularly duodenal) involvement possible in otherwise typical UC


  • Extraintestinal manifestations



    • Arthralgias


    • Primary sclerosing cholangitis (PSC)



      • Fibroinflammatory disease of biliary tree


      • ˜ 5% of UC patients also have PSC


      • ˜ 70% of PSC patients have UC


Presentation



  • Abdominal pain


  • Diarrhea



    • May occur dozens of times/day


    • Constipation possible in left-sided disease (due to left colonic spasm “trapping” stool in right colon)


  • Fecal urgency



  • Fever


  • Hematochezia


  • Tachycardia


  • Ulcer


  • Weight loss


Endoscopic Findings



  • Contiguous mucosal inflammation



    • Evidence of disease activity



      • Mucosal erythema


      • Shallow ulcers


      • Fresh blood, mucosal oozing


    • Evidence of chronic inflammation and mucosal injury



      • Loss of normal vascular pattern


      • Mucosal granularity


      • Loss of normal mucosal folds


  • Correlation of histological and endoscopic findings essential for accurate diagnosis



    • Allows accurate determination of disease distribution


    • Ideally, endoscopic report should be available for review by pathologist


    • Knowledge of biopsy sites and appearance of mucosa biopsied are important


  • Grossly/endoscopically normal mucosa may be inflamed



    • Both normal- and abnormal-appearing mucosa should be biopsied throughout colon


  • Colons with longstanding disease may have extensive changes



    • Flat, featureless mucosa


    • Foreshortened, tube-like anatomy



      • Caused by smooth muscle contraction and mucosal changes


  • Precise endoscopic appearance of any “polyps” or areas of raised mucosa important



    • Evidence of colitis-associated dysplasia must be sought



      • Raised dysplasia often has unusual, worrisome endoscopic appearance


      • Dysplasia may be endoscopically invisible (flat dysplasia)


    • Sporadic adenomas and other polyps also possible in UC patients



      • Biopsy of “polyps” should prompt discussion with endoscopist as to exact appearance


      • Must know whether polyp was within area affected (currently or historically) by colitis


    • “Filiform” polyps → long, finger-like or worm-like mucosal projections into colonic lumen



      • Essentially old inflammatory polyps


      • May be extensive in longstanding disease (“filiform polyposis”)


Laboratory Tests



  • Serology



    • Antineutrophil cytoplasmic antibodies (ANCA)



      • Occur more often in UC than in CD patients


    • Anti-Saccharomyces cerevisiae antibodies (ASCA)



      • Occur in CD patients


    • May be helpful in establishing diagnosis in difficult cases


Natural History



  • Classically characterized by periods of remission and relapse (“UC flares”)



    • 1st onset may be abrupt


    • Most have distal disease (proctitis) at presentation



      • May continue as proctitis or spread more proximally over time


      • Some patients present with more extensive colitis (including pancolitis)


    • Remissions



      • Some patients essentially symptom-free between periods of activity (“recurrent colitis”)


      • Others have continuous disease with waxing and waning severity


  • Toxic megacolon



    • Severe UC complication occurring in small number of patients


    • Characterized by extensive dilation, loss of colonic motility, and thinning of wall




      • May lead to mural necrosis and perforation


    • Usually occurs in patients with pancolitis


  • Colitis-associated dysplasia



    • Markedly increased risk of dysplasia/neoplasia in IBD (1-2% increased carcinoma risk each year after 10 years)



      • Develops in areas affected by chronic inflammation


      • Can be flat (endoscopically invisible) or raised (dysplasia-associated lesion/mass [DALM])


      • Risk directly related to duration and extent of disease


Treatment



  • Surgical approaches



    • Colectomy may be urgent/emergent or elective



      • Urgent indications: Fulminant colitis, perforation, intractable bleeding, toxic megacolon


      • Elective indications: Failed medical therapy, development of dysplasia/carcinoma


    • Definitive operation → total abdominal colectomy with ileal pouch-anal anastomosis (IPAA)



      • Most patients have so-called ileal J-pouch created → serves as fecal reservoir


      • Interim ileostomy may be constructed, particularly when surgery is emergent


  • Drugs



    • 1st line therapy (effective in mild-moderate disease)



      • 5-aminosalicylic acid (5-ASA, mesalamine)


      • Corticosteroids


    • Refractory or continuously active disease



      • Azathioprine


      • 6-mercaptopurine (6-MP)


      • Other immunomodulators (tacrolimus, methotrexate, infliximab)


    • Novel therapies



      • Probiotics → alter luminal flora (may be beneficial as adjunctive therapy)


Prognosis



  • Chronic, usually unrelenting disease


  • High probability of active disease (˜ 75%) in any year following year in which disease was active


MACROSCOPIC FEATURES


General Features



  • Mucosal abnormalities in active disease



    • Granularity and erythema


    • Pseudopolyps



      • Inflamed projections of regenerative mucosa created when ulcers undermine adjacent mucosa


      • May impart “cobblestone” appearance to mucosa if multiple


    • Shallow ulcers


    • Adherent blood &/or mucopurulent exudate


  • Chronic changes



    • Flattened, finely granular mucosa


    • Muscular contraction and mucosal fibrosis may lead to rigid, “foreshortened” colon


  • Disease distribution



    • Should be described in relation to normal anatomical landmarks


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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Ulcerative Colitis, Colon

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