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Ulcerative Colitis: Definition, Clinic, Diagnosis, Differential Diagnosis, Therapy, Prognosis and Complications

Source: www.mayoclinic.org


    UC is a chronic inflammatory disease affect the mucosa of the large intestine, usually begins at rectum and extends proximally (just 5% of cases without rectum involvement, third of cases in pediatric onset). 
    It is characterized by recurring episodes of inflammation with periods of remissions, some patients have persistent disease activity, and a small number of patients present with fulminant disease


    The condition may present at any time and at all ages, but there is a predominant age distribution of onset that peaks between ages 15 and 30 years.
    In North America, incidence rates range from 2.2 to 19.2 cases per 100,000 person-years

    Clinical manifestation

    -        Diarrhea with/without blood
    -        colicky abdominal pain, urgency, tenesmus, and incontinence 
    -        Patients with mainly distal disease may have constipation accompanied by frequent discharge of blood and mucus.
    -        systemic symptoms including fever, fatigue, and weight loss.
    -        Complications such as anemia due to bleeding and iron deficiency with palpitations, dyspnea.
    Disease activity: The severity of disease activity can be objectively measured using a clinical disease activity index, such as the 1- Montreal classification of severity of ulcerative colitis:
    • Mild:
    -        four or fewer stools per day with or without blood
    -        no signs of systemic toxicity
    -        normal erythrocyte sedimentation rate (ESR).
    -        Mild crampy pain, tenesmus, and periods of constipation
    -        severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease.
    • Moderate:
    -        Frequent loose, bloody stools (>4 per day)
    -        Patients have minimal signs of systemic toxicity, including a low-grade fever.
    -        mild anemia not requiring blood transfusions
    -        abdominal pain that is not severe.
    -        Adequate nutrition is usually maintained, and weight loss is not associated with moderate clinical disease.
    • Severe: 
    -        frequent loose bloody stools (≥6 per day)
    -        severe cramps
    -        evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5ºC), tachycardia (HR ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30 mm/hour). 
    -        Patients may have rapid weight loss.
    Other scores to estimate the severity of UC 2- MAYO-Score:

    Source: ACG Clinical Guideline: Ulcerative Colitis in Adults

    Extraintestinal manifestations: present in up to 25% of patients:
    ·        Musculoskeletal:
    -        nondestructive Arthritis which primarily involves large joints
    -        ankylosing spondylitis.
    -        osteoporosis, osteopenia, and osteonecrosis.

    ·        Eye: 
    -        uveitis and episcleritis
    -        Scleritis, iritis, and conjunctivitis

    ·        Skin 
    -        erythema nodosum
    -        pyoderma gangrenosum

    ·        Hepatobiliary: 
    -        Primary sclerosing cholangitis
    -        fatty liver
    -        autoimmune liver

    ·        Hematopoietic/coagulation:
    -        increased risk for both venous and arterial
    -        Autoimmune hemolytic anemia (AIHA) has been associated with IBD.


    ·        History: 
    -        recent travel to areas endemic for parasitic infections: amebiasis?
    -        recent antibiotic use: Clostridium difficile?
    -        Sexual anamneses: sexually transmitted diseases? Neisseria gonorrhea and herpes simplex virus (HSV) are associated with proctitis!
    -        Atherosclerotic disease or prior ischemic episodes: chronic colonic ischemia?
    -        history of abdominal/pelvic radiation and NSAID/medication 
    -        In an immunocompromised patient, cytomegalovirus (CMV) can mimic ulcerative colitis. 

    ·        Laboratory:
    -        HGB: anemia? iron deficiency?  Signs of hemolysis?   
    -        ESR, CRP: elevated?
    -        Electrolyte: abnormalities due to diarrhea
    -        Kidney and lever functions tests
    -        APH: elevated by PSC
    -        pANCA may be elevated but its rule in the diagnosis is unclear

    ·        Stool tests:
    -        Clostridium difficile toxin
    -        stool cultures (Salmonella, Shigella, Campylobacter, Yersinia, and specific E. coli 0157:H7)
    -        Microscopy for ova and parasites (three samples)
    -        Giardia stool antigen test
    -        Calprotectin: elevated

    ·        Serologic testing for sexually transmitted diseases
    -        Neisseria gonorrhea
    -        HSV
    -        Treponema pallidum 
    -        CMV by Immunosuppressed

    ·        Coloscopy:
    -         Colonoscopy with intubation of the ileum and biopsies of affected and unaffected areas should be obtained
    -         Extend of the disease: according to Montreal classification:
    1-     (E1) proctitis (within 18 cm of the anal verge, distal to the rectosigmoid junction) 30-50%
    2-     (E2) left-sided colitis (extending from the sigmoid to the splenic flexure), 20-30%
    3-     (E3) extensive colitis (beyond the splenic flexure). 20%
    -        Endoscopic severity of UC can be evaluated with different indexes, such as Ulcerative Colitis Endoscopic Index of Severity UCEIS:

    Source: ACG Clinical Guideline: Ulcerative Colitis in Adults
    -        The biopsy features suggestive of ulcerative colitis include:
    Crypt abscesses, and crypt atrophy.
    Increased lamina propria cellularity
    Basal plasmacytosis, basal lymphoid aggregates
    Lamina propria eosinophils.
    None of these features are specific for ulcerative colitis, the presence of two or more histologic features is highly suggestive of ulcerative colitis 

    Differential Diagnosis

    • Crohn's disease: Features that are suggestive of Crohn’s disease include absence of gross bleeding, presence of perianal disease (eg, anal fissures, anorectal abscess), and fistulas. The absence of rectal inflammation and the presence of ileitis, focal inflammation, and granulomas on endoscopy and biopsy are also suggestive of Crohn’s disease. 
    • Infectious colitis: stool and tissue cultures.
    • Radiation colitis: Radiation colitis may be seen weeks to years after abdominal or pelvic irradiation. histologic findings suggestive of radiation colitis include eosinophilic infiltrates, epithelial atypia, fibrosis, and capillary telangiectasia.
    • Solitary rectal ulcer syndrome: Patients with solitary rectal ulcer syndrome may have bleeding, abdominal pain, and altered bowel habits. Mucosal ulceration may be seen on endoscopy similar to ulcerative colitis, but solitary rectal ulcer syndrome has a characteristic appearance on histology with a thickened mucosal layer and distortion of crypt architecture. The lamina propria is replaced with smooth muscle and collagen leading to hypertrophy and disorganization of the muscularis mucosa.
    • Graft versus host disease: Graft versus host disease (GVHD) of the colon can cause chronic diarrhea in patients with a history of bone marrow transplantation. Patients may have symptoms due to involvement of other organs (eg, liver). Histologic examination in chronic GVHD is characterized by the presence of crypt cell necrosis with the accumulation of degenerative material in the dead crypts.
    • Medication associated colitis: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause chronic diarrhea and bleeding.  The diagnosis is established by a history of medication use and the presence of nonspecific mucosal inflammation or mucosal erosions on biopsy that resemble ischemic changes.


    therapy has two goals: to induce remission and to maintain it.
    Therapeutic management in UC should be guided by assessment of disease activity (i.e., mild, moderate, or severe), and disease prognosis.
    Mild diseased patients with bad prognose factors are to be treated as severe diseased patients.

    1-   mildly active UC:
    -        Proctitis: rectal 5-ASA 1g/d
    -        Left-sided UC: 5-ASA Enema 1 g/d alone or in combination with oral 5-ASA 2 g/d, by intolerance or nonresponsive: oral budesonide multi-matrix (MMX) 9 mg/d.
    -        Extensive UC: oral 5-ASA 2 g/d.
    -        higher dosage of 5-ASA has no more difference in the remission rate 
    -        Symptomatic improvement and a decrease in bleeding can be seen within a few days.

    Maintenance of remission in patients with previously mildly active UC:

    -        Proctitis: rectal 5-ASA 1g/d
    -        Left-sided/Extensive colitis: oral 5-ASA 2 g/d.

    -        Systemic steroids: Prednisolone 30 mg x2/d or budesonide multi-matrix (MMX) 9 mg/d.
    -        Oral 5-ASA as combination therapy with steroids: 4.8g/d
    -        Local 5-ASA/Steroids may help
    Caution: 5-ASA may cause Exacerbation of the disease in some rare cases, and should be discontinued
    -        When systemic toxicity with fever è consider antibiotics: Ciprofloxacin+ Metronidazole
    -        When no meaningful clinical response after 7-10 days of intravenous therapy with steroids è consider anti-TNF: Infliximab

    Maintenance of remission in patients with MODERATELY TO SEVERELY ACTIVE UC:

    -        Begin steroid taper 2-4 weeks after patient has been stabile
    -        Taper Steroid over 8 weeks: 10 mg/week until 20 mg/d then 2.5/week
    -        Local steroids/5-ASA should be tapered over 2-4 months
    -        Oral 5-ASA should be continued at the same dose 4.8 g/d

    When: (
    1-   Steroid-dependent:
    -        glucocorticoids cannot be tapered to less than 10 mg/day within three months of starting glucocorticoids without recurrent disease
    -        or relapse occurs within 3 months of stopping glucocorticoids.
    2-   Steroid-refractory:
    -        No significant response on steroid 40-60 mg p.o. within 30 days
    -        Or 40-60 mg i.v. within 7-10 days
    3-   Severe ulcerative colitis with >2 relapses requiring glucocorticoids in 12 months despite optimal doses of oral 5-ASA medication
    4-   Patients who cannot tolerate 5-ASA.
    è consider: 6-mercaptopurine (6-MP)/ azathioprine (AZA) or an anti-TNF           agent for maintenance of remission:
    1-   AZA: 2 mg/kg/day WHEN patient take steroid and benefit from it (dependent) è Steroid reduction after 2-4 weeks due to the schemata above. AZA takes 3-6 months till effect.
    2-   When Steroid-refractory then the patient can’t wait till AZA takes its effect è fast-acting Agent Cyclosporine: 2-4 mg/kg/day as continuous infusion
    -        Effect to be seen after 3 days: (no pain, consistent stools, patients can eat)
    -        Then give it as oral therapy with the double doses 4-8 mg/kg divided om 2 time a day
    -        Continue steroid therapy as above (oral) with successive reduction after 4-6 weeks of begin
    -        Start reduction of cyclosporin after 6-8 weeks of begin
    -        Begin AZA 2mg/kg/day therapy 1 week after beginning with oral cyclosporin therapy.
    -        Cyclosporin levels in blood should be taken every 2-3 days: by 4 mg/kg i.v. 300-400 ng/ml, by oral therapy 200-300 ng/ml, under 200 ng/ml no response
    3-   When AZA is not an option due to allergy or has already failed then a bridge therapy with cyclosporin has no Sinn è Infliximab: can be used to both initiation a remission and maintain it. 5-10 mg/kg at week 0.2.6 and then every 8 weeks.

    Surgical therapy: 
    20-30% of Patients will require OP.
    -        Cyclosporin fails to achieve improvement in 3 days of i.v. therapy
    -        Infliximab fails to achieve remission
    -        Side effects of medication are intolerable
    -        Dysplasia or Coloncancer
    -        Acute fulminant UC with acute Abdomen
    -        Acute fulminant UC without acute Abdomen, when Cyclosporin/Infliximab fails to induce Remission within 4-7 days, or by toxic megacolon within 3 days.
    ð  Consider Colectomy

    Fulminant colitis is subgroup severe ulcerative colitis with:
    -         > 10 stools per day
    -        continuous bleeding
    -        abdominal pain, distension
    -        acute, severe toxic symptoms including fever and anorexia.
    -        risk of progressing to toxic megacolon and bowel perforation.

    -        Admission to a hospital
    -        vital signs and physical examination every four to six hours
    -        A complete blood count, serum electrolytes, serum albumin, liver function tests, and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) should be checked every 12 to 24
    -        Patients should be kept NPO. Nutritional support should be considered if the patient is malnourished.
    -        Intravenous fluid and electrolyte replacement are necessary to correct and prevent dehydration or electrolyte imbalance.
    -        Blood transfusions may be needed to maintain a hemoglobin ≥10 g/dL.
    -        Patients with intestinal dilation (transverse colon diameter ≥5.5 cm) should receive decompression with a nasoenteric tube. Intermittent rolling maneuvers every two hours or the knee-elbow position should be recommended.
    -        Plain abdominal radiography should be repeated if there is clinical deterioration to determine if there is colonic dilation (diameter ≥5.5 cm) or toxic megacolon (diameter ≥6 cm or cecum >9 cm and systemic toxicity).
    -        intravenous glucocorticoids. Prednisolone (30 mg IV every 12 hours)
    -         broad-spectrum antibiotics (eg, ciprofloxacin 400 mg every 12 hours and metronidazole 500 mg every eight hours).
    -         When fail to improve by the third day of intensive treatment è cyclosporine or infliximab or undergo colectomy.
    -        Cyclosporine  Intravenous as a short-term "bridge" to therapy with the slower onset, longer acting medications, including azathioprine (AZA) or 6-mercaptopurine (6-MP).
    -        Infliximab: can induce remission rapidly and can be used for the maintenance of remission. For patients with an allergy to AZA/6-MP or who have failed to AZA/6-MP. 
    -        Colectomy When Patients with fulminant colitis fail treatment with cyclosporine or infliximab within four to seven days and those with toxic megacolon who do not respond to therapy within 72 hours.


    -        Relapse in 10 years after diagnosis:  67 %
    -        Extension of colonic disease is seen in up to 20 % of patients within five years.
    -        Approximately 20 to 30 % of patients with ulcerative colitis will require colectomy for acute complications or for medically intractable disease.
    -        Poor prognostic factors in ulcerative colitis.

    Source: ACG Clinical Guideline: Ulcerative Colitis in Adults


    • Severe bleeding:
    in up to 10% of Patients
    • Fulminant colitis and toxic megacolon:
     Fulminant colitis: is defined as:  
    -        >10 stools per day
    -        continuous bleeding
    -        abdominal pain, distension
    -        acute, severe toxic symptoms including fever and anorexia.

    Toxic megacolon: is characterized by:
    -        colonic diameter ≥6 cm or cecal diameter >9 cm
    ·        The presence of systemic toxicity (fever (temperature ≥37.5ºC), tachycardia (HR ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30 mm/hour). 

    ·        Perforation: 

    Perforation of the colon most commonly occurs as a consequence of toxic megacolon but may also occurs without megacolon. Mortality by perforation with consequent peritonitis up to 50%.
    • Stricture:
    Benign strictures can occur due to repeated episodes of inflammation and muscle hypertrophy in about 10 % of cases with ulcerative colitis
    • Dysplasia or colorectal cancer:
    the cumulative incidence of CRC was 2.5 % after 20 years and 7.6 % after 30 years of disease

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