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					   Diagnosis
        &
  Management
        of
Ulcerative Colitis
                   Epidemiology

• Ulcerative colitis is a World-Wide disease
• Incidence (new cases):
    – 5 cases per 100,000
    – High incidence in White Population (Northern Europe, North America)
    – The incidence is increasing in the black population
• Prevalence (patients):
    – 50 cases per 100,000


• Equal male/female incidence

•   Peak presentation
    – 1st peak between 15-25 years of age
    – 2nd peak between 55-65 years of age



                                        Cecil textbook of Medicine p. 722, 21st Edition, 2000
    Factors associated with increased
                incidence
• First degree relatives
• Identical twins
• Associated with autoimmune thyroiditis & SLE
• Patients with HLA B27 develop ankylosing
  spondylitis
• More common in non smokers & ex smokers
• Associated with low fiber & high refined sugar
  diet
            Ulcerative Colitis
                   Etiology
Inflammation                                         Genetics




                  ULCERATIVE
                    COLITIS


Immuno-
                                                    Infection
pathology



                        Cecil textbook of Medicine p. 722, 21st Edition, 2000
           Ulcerative Colitis

• Ulcerative colitis is a chronic inflammatory
  disease of colon of unknown cause
• Pursue a protracted relapsing & remitting
  course
• Always affects the rectum
• Extends proximally to involve a variable
  extent of the colon




                             Oxford Textbook of Medicine p. 1943, Vol. 2, 3rd Edition 1996
      U.C Disease Distribution at Presentation

            Pancolitis                                                             n=1116
                                                                  Ulcerative proctitis
                                      37% ENTIRE                  or Proctosigmoiditis
                                        COLON

                                                      46% RECTO
                                                       SEGMOID


                                             17%
                                            COLON
                                          UPTO LEFT
                                           FLEXURE




     Left Sided Colitis



Farmer RG. Dig Dis Sci;38:1137-1146
         Ulcerative Colitis
Pathology

– Inflammatory reaction primarily involving the colonic mucosa

– Grossly the colon appears ulcerated, hyperemic, and usually
  hemorrhagic

– Inflammation is uniform and continuous with no intervening
  areas of normal mucosa

– Rectum is usually involved (95% of the cases)

– Inflammation extend proximally in a continuous fashion but
  for a variable distance

                                Harrison’s Principles of Internal Medicine, p.1404, Vol 2, 13th Edition 1995
          Ulcerative Colitis

Symptoms: depend on site & activity of
 disease
• Proctitis : Rectal bleeding, mucus discharge &
  tenesmus
• Proctosigmoiditis: Bloody diarrhea, mucus &
  those with active disease have fever, lethargy &
  abdominal discomfort
• Extensive Colitis: Severe bloody diarrhea, mucus,
  fever, weight loss, malaise, abdominal pain,
  tachycardia



                 Davidson’s Principles& practice of Medicine, 19th edition
            Ulcerative Colitis
Clinical Course

• 60-75% of patients will have intermittent flares
  interrupted by periods of complete clinical remission

• 5-45% of patients unable to attain clinical remission;
  they have chronic unremitting symptoms

• 10% will have one attack and enter permanent
  clinical remission (probably misdiagnosed infectious
  colitis)
                 Ulcerative Colitis
  Relapses
• Six major factors thought to be responsible
   – Failure to comply with a maintenance regimen
   – Mesalamine sensitivity
   – Activation of eosinophils by environmental stimuli,
     including seasonal changes
   – Systemic and enteric infection
   – Use of NSAIDs / antibiotics
   – Changes in smoking status
   – Emotional stress
    Assessment of disease severity

VARIABLE            MILD           SEVERE           FULMINANT


Stools (no./ day)   <4             >6               >10

Blood in stool      Intermittent   Frequent         Continuous

Temperature         Normal         >37.5            >37.5

Pulse               <90            >90              >90
(beats/min)

Hemoglobin          Normal         <75% of normal   Transfusion
                                   value
Erythrocyte         Normal         >30              >30
sedimentation
rate (mm/hr)
              Ulcerative Colitis
Clinical Grading
• Mild
   – Less than four stool daily, with or without blood,
   – No systemic disturbance and normal ESR
• Moderate Between mild and severe
• Severe
   – At-least six stools daily, with bleeding
     Fever, Tachycardia, Falling Hemoglobin, Hypoalbuminaenia,
     Raised ESR and C-reactive protein




                                Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
               Ulcerative Colitis
Extra-intestinal manifestations
• Related to activity of colitis
    – Aphthous ulceration of the mouth

    – Fatty liver

    – Erythema nodosum

    – Peripheral arthropathy

    – Liver abscess / portal pyemia

    – Mesentric / Portal vein thrombosis

    – Conjunctivitis / Iritis / episcleritis / venous thrombosis


                                   Oxford Textbook of Medicine p. 1948, Vol. 2, 3rd Edition 1996
               Ulcerative Colitis
Extra-intestinal manifestations of ulcerative colitis

• Usually related to activity of colitis
    – Pyoderma gangrenosum

    – Anterior uveitis

• Unrelated to colitis
    – Ankylosing spondylitis

    – Primary sclerosing cholangitis / Autoimmune hepattis

    – Cholangiocarcinoma

    – Gall stones

    – Amyloidosis
                                Oxford Textbook of Medicine p. 1948, Vol. 2, 3rd Edition 1996
          Ulcerative Colitis

Complications
  – Anemia
  – Hemorrhage
  – Toxic megacolon, perforation & peritonitis
  – Electrolyte disturbances
  – Dehydration
  – Strictures, benign and malignant
  – Cancer: patients ewith disease of > 8 years
    duration are at risk
                Harrison’s Principles of Internal Medicine, p.1408, Vol 2, 13th Edition 1995
            Ulcerative Colitis

Diagnosis
• History
• Stool culture
• Sigmoidoscopy
• Colonoscopy
• Radiology




                    Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
            Ulcerative Colitis
Stool Culture


   – Performed to exclude superimposed infection in those
     who presents with exacerbations

   – Special culture conditions are required for
     Campylobacter spp., Yersinia, Gonococci and
     Clostridium difficile

   – Possibility of an infection with E. coli must be
     considered, specially when bleeding and abdominal
     pain are predominant symptoms
                         Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
          Ulcerative Colitis

Sigmoidoscopy
• To evaluate for pattern and character of mucosal
  inflammation

• To obtain biopsies for confirmation

• The early sign of colitis on sigmoidoscopy are
  blurring of the vascular pattern associated with
  hyperemia and edema, leading to blunting of the
  valves of houston



                        Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
             Ulcerative Colitis

Sigmoidoscopy

• In severe cases the mucosa becomes granular and than
  friable

• With severe inflammation the mucosa shows spontaneous
  bleeding and ulceration, these changes begin in the
  rectum, they are diffuse, and extend proximally to affect a
  variable length of the colon




                           Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
          Ulcerative Colitis
Colonoscopy

• Colonoscopy with multiple biopsies is useful for
  assessing the extent of disease and is mandatory for
  patients with a colonic stricture
• May show pseudopolyposis or a cancer

• Biopsies specimens must be taken at sigmoidoscopy
  or colonoscopy preferably with small, cupped
  forceps.

• Histological assessment contributes to grading
  severity as well as the differential diagnosis
                        Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
              Ulcerative Colitis
Laboratory Data

• Iron deficiency is common as a result of chronic iron loss

• Neutrophilic leucocytosis, thrombocytosis, esinophilia or
  monocytosis may also be present ,indicators of active
  inflammation

• Biochemical abnormalities are rare in mild or moderate attack

• Hypokalaemia, hypoalbuminaemia, and a rise in 2-globulin
  frequently accompany a severe attack

• Serum immunoglobulins rarely exceed the upper limit of normal
  during a relapse but usually fall as remission occurs

                             Oxford Textbook of Medicine p. 1946, Vol. 2, 3rd Edition 1996
             Ulcerative Colitis
Radiology
• Barium enema may reveal the extent of the disease

• Helps define associated features such as stricture,
  pseudopolyposis, or carcinoma

• The earliest feature is incomplete filling due to associated
  inflammation

• In the chronic stage, the characteristic features are shortening
  of the bowel, depression of the flexures, narrowing of the
  bowel lumen, and rigidity



                     Harrison’s Principles of Internal Medicine, p.1409, Vol 2, 13th Edition 1995
            Ulcerative Colitis
Medical Management

• The main principles of therapy for the treatment are:


   – Control active disease rapidly
   – Maintain remission
   – Detect cancer at an early stage
   – Select patients for whom surgery is appropriate
   – Ensure as good a quality of life as possible


                          Oxford Textbook of Medicine p. 1943, Vol. 2, 3rd Edition 1996
           TREATMENT
• PROCTITIS
 Mesalamine suppositories 500 mg /
  rectum BD or
Hydrocortisone suppositories 100 mg OD
• PROCTOSIGMOIDITIS
Mesalamine Enema 4 gm OD
Hydrocortisone Enema 100 mg OD
             TREATMENT
• EXTENSIVE COLITIS (mild-mod.)
Mesalamine tab 2.4-4.8 g / d or
Sulfasalazine 1.5-3 g / bd
Add prednisolone: Initially enema & then
  oral 40-60 mg / d if no response after 2-4 w
              TREATMENT
• SEVERE COLITIS
 Hospitalization
 Stop all oral intake
 Correct fluid & electrolytes
 Transfusion for anemia
 Plain X ray abdomen to look for dilatation
 Methylprednisolone IV 48-64 mg or
  hydrocortisone 300 mg
 Surgery: If no response after 7-10 days of steroids
            TREATMENT
• FULMINANT COLITIS
Severely ill with fever, dehydration
Risk of perforation or toxic megacolon
Antibiotics for anaerobes & Gm-ve bacteria
N/G tube suction
If fail to improve within 48-72 hr, surgery
  indicated
           TREATMENT
• REMISSION MAINTAINANCE
75% relapse within one year without
  maintainance therapy
Mesalamine 800 mg TDS or sulfasalazine
  1-1.2 g bd
Decrease relapse rate to < 33%
            TREATMENT
• REFRACTORY DISEASE
Patients who refuse surgery may be given
  immunosuppressive drugs
Azathioprine OR Mercaptopurine benefit
  60% patients
Infliximab 5mg / kg benefits some patients
  with refractory disease
ASACOL    ™

The Drug of
  Choice
Colon Cancer
     Cumulative Incidence for Colorectal Cancer Based on
           Extent of Disease at Time of Diagnosis

         40
                    pancolitis
         30         left-sided colitis
Cumulative
 CRC (%) 20

         10

          0
              0       10          20       30        40
                           Years follow-up

                                         Ekbom, et al NEJM, 1990
             Ulcerative Colitis


 Conclusion

– First choice is an aminosalicylate, depending on which one the
  patient can tolerate. Aminosalicylates generally are effective and
  have minimal side effects.

				
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