ULCERATIVE COLITIS

BY

AHMED FAWZY SELIM

Assistant lecturer of Internal Medicine

Faculty of medicine – Tanta university

Definition of UC

• Ulcerative colitis is a diffuse non-specific inflammatory disease of the large intestine of unknown cause, primarily affecting the mucosa, characterized by erosions and/or ulcerations. The disease is characterized by repeated cycles of relapses and remissions, occasionally accompanied by extra-intestinal manifestations.

Epidemiology of UC

• Ulcerative colitis is more common in the Western and Northern hemispheres with highest incidence in USA and UK.

• In the Past 2 decades , its incidence increased in Middle east and Asia and may be due to westernization of diet .

• Ulcerative colitis is slightly more common in women than in men. Age of onset around 15-25 years, although the disease can occur in people of any age. Ulcerative colitis is uncommon in persons younger than 10 years.

Etiology of UC• the exact etiology of ulcerative colitis is

unknown, but certain factors have been found to be associated with the disease, include genetic factors, immune system reactions, environmental factors, nonsteroidal anti-inflammatory drug (NSAID) use, low levels of antioxidants, psychological stress factors, and consumption of milk products.

• The incidence of UC is lower in smokers than in nonsmokers.

• Ingestion of animal fat can increase the occurrence of UC.

• A history of appendectomy is correlated

negatively with the occurrence of UC.

Pathophysiology • A variety of immunologic changes have been

documented in UC. T cells accumulate in the lamina propria of the diseased colonic segment. these T cells are cytotoxic to colonic epithelium. This change is accompanied by an increase in the population of B cells and plasma cells, with increased production of immunoglobulin G (IgG) and immunoglobulin E (IgE).[9]

• Anticolonic antibodies have been detected in patients with UC. A small proportion of patients with ulcerative colitis have smooth muscle and anticytoskeletal antibodies.

• Microscopically, acute and chronic inflammatory infiltrate of the lamina propria, crypt branching, and villous atrophy are present in ulcerative colitis. Microscopic changes also include inflammation of the crypts of Lieberkühn and abscesses. These findings are accompanied by a discharge of mucus from the goblet cells, the number of which is reduced as the disease progresses. The ulcerated areas are soon covered by granulation tissue. Excessive fibrosis is not a feature of the disease. The undermining of mucosa and an excess of granulation tissue lead to the formation of pseudopolyps.

Clinical presentation

• A major symptom of UC is bloody diarrhea, occasionally accompanied by abdominal pain

• UC should be suspected in cases with a history of persistent or repetitive mucous bloody stool/bloody feces.

• Patients with UC often have no abnormal findings on physical examination, but anemia, weight loss, abdominal tenderness and fresh bleeding on digital rectal examination are occasionally seen.

Classification of ulcerative colitis by severity

Classification by the extent of the lesions

Extra-intestinal manifestations of UC

• Extraintestinal IBD-related immune disease can be classified into two major groups:

• The first one includes reactive manifestations often associated with intestinal inflammatory activity and therefore reflecting a pathogenic mechanism common with intestinal disease (arthritis, erythema nodosum, pyoderma gangrenosum, aphthous stomatitis, iritis/

uveitis)• The second one includes many autoimmune

diseases independent of the bowel disease that reflect only a major susceptibility to autoimmunity.

Major extraintestinal immune-related manifestations of IBD

• Arthritis

• Erythema nodosum• Pyoderma gangrenosum• Aphthous stomatitis• Iritis/uveitis

Autoimmune disorders associated to IBD

• Alopecia areata• Ankylosing spondylitis• Cold urticaria• Hemolytic anemia• Henoch-Schoenlein purpura• Insulin-dependent diabetes mellitus• Pancreatitis• Primary biliary cirrhosis• Primary sclerosing cholangitis• Polymyositis• Raynaud phenomenon• Seropositive rheumatoid arthritis• Sjogren syndrome• Thyroid disease• Vitiligo• Wegener’s granulomatosis

Extra – intestinal complication of IBD

• Anemia due to Iron deficiency, inflammation• Thromboembolic events from Hypercoagulopathies,

platelet activation• Osteopathy due to Steroid therapy, vitamin D deficiency

inflammation• Growth failure and Malnutrition

• Urinary stones from Dehydration, hyperoxaluria, low urinary PH

• Gall bladder stones from Intestinal loss of bile acids

• Amyloidosis Acute phase reaction, chronic inflammation• Fatty liver from Malnutrition

Diagnostic criteria of UC

(A) Symptoms: continuous or repeated bloody diarrhea;

(B) endoscopy: diffuse inflammation, loss of vascular pattern, friability

(bleeding at contact), abundant mucus and (i) granular appearance;

(ii) multiple erosions, ulcers; and (iii) pseudopolyps, loss of haustration (lead-pipe pattern), lumen narrowing, and colonic shortening.

(C) Histology: active: inflammatory cells infiltration, crypt

abscess, goblet cell depletion. Remission: crypt architectural

abnormalities (distortion branching), atrophic crypts.

These changes usually begin in the rectum and extend proxi-mally in continuity.

Definite diagnosis: A+one item of B and C.

Investigations

1- Colonoscopy is the basic tool for diagnosis of UC

Typically, UC shows endoscopic findings such as loss of vascular pattern, granular mucosa, easy

bleeding, and ulceration in a continuous manner.

The mucosa is involved diffusely, the vascular pattern cannot be observed, and a coarse or microgranular

appearance is noted. Furthermore, the mucosa is fragile and easy to bleed by contact. Mucous/bloody/

puriform secretions, multiple erosions, ulcers and/or pseudopolyposis are observed

2-Serological markers

- ANCA is most commonly associated with ulcerative colitis while ASCA is more highly associated with Crohn disease and is present in 60% of cases

3- Markers of activity

a) Acute phase reactants ESR , CRP , TLC

b) Fecal calprotectin can reflect the severity of the disease

4- Radiological assessment

• Double-contrast barium enema examination is a valuable technique for diagnosing ulcerative colitis even in patients with early disease.

• Cross-sectional imaging studies (eg, US, MRI, CT scanning) are useful for showing the effects of these conditions on the wall of the bowel.

• Radionuclide studies are useful in cases of acute fulminant colitis when colonoscopy or barium enema examination is contraindicated

Comparison between UC and Crohns disease

I-Remission induction therapy for active distal colitis

• The basic drugs that are used in the treatment of mild to moderate distal colitis are oral ASA preparations,

topical 5-ASA preparations and topical steroids.

• The optimal dose level of 5-ASA enema for mild to moderate distal colitis is 1 g/day.

• When used for the treatment of active distal colitis, 5-ASA enema is superior to steroid enema in terms of improvement of the clinical symptoms, endoscopic findings and histological findings.

• It is not uncommon to find that 5-ASA enema is effective even in patients with active distal colitis who do not respond to steroid enema.

• The efficacy of a combination of oral and topical 5-ASA therapy is superior to that of either drug alone.

• Treatment of active distal colitis resistant to 5-ASA preparations

In cases who do not respond to oral 5-ASA therapy at an optimal dose combined with topical 5-ASA or steroid therapy, oral PSL (prednisolone) should be started at a daily dose of 30-40 mg.

• In January 2013, the US Food and Drug Administration (FDA) approved an extended-release oral formulation of budesonide for the treatment of active mild-to-moderate ulcerative colitis in adults patients.Because budesonide is a potent corticosteroid that exerts only minimal systemic activity, this formulation provides the benefit of a potent anti-inflammatory drug delivered locally while avoiding many of the systemic side effects associated with systemic steroids.

• Budesonide rectal foam was approved in October 2014 and is indicated for the induction of remission in adults with active mild-to-moderate distal ulcerative colitis extending up to 40 cm from the anal verge

II- Remission induction therapy for mild to moderate total colitis and left sided colitis

• Treatment is started with oral ASA preparations. SASP (2-6 g/day) can induce remission in 50-80% of all cases

• In patients who do not respond to ASA preparations or require rapid alleviation of symptoms, PSL is administered orally at the dose of 30-40 mg/day.

• It has been shown in a meta-analysis of multiple RCTs that in patients with active left-sided colitis, remission can often be induced by topical 5-ASA therapy alone and this therapy is superior to oral systemic drug therapy. “Comparing the efficacy between 5-ASA enema and steroid enema, many studies demonstrated superiority of 5-ASA.

III-Treatment of severe ulcerative colitis

• Patients failing to respond to maximum oral/topical treatment or those satisfying the criteria of severe

disease are generally required to be hospitalized and to receive intravenous steroid therapy and intravenous alimentation.

• The optimal steroid dose level for intravenous administration is 1-1.5 mg/k/day

• In patients who does not respond to 7-10 days of intensive steroid therapy, continuation of steroid is not expected to improve the efficacy, and surgical treatment or cyclosporine is indicated the optimal cyclosporine dose is 2 mg/kg

• Combined use of antimicrobial agents such as ciprofloxacin with steroid therapy for severe UC does not

improve the responses. • Antimicrobial agents are used only in cases possibly

complicated by infection and patients immediately

before surgery.

• Anticholinergics, antidiarrheal agents, NSAIDs, narcotics, etc., should be discontinued.

• Infection with C. difficile or CMV needs to be checked during treatment.

• According to a recent large-scale multicenter study conducted overseas, infliximab was useful for both inducing and maintaining remission in patients with therapy-resistant moderate to severe UC. In the USA, the use of infliximab in UC patients has been approved by the FDA.

IV- maintenance therapy

• None of commonly employed dietary restriction has been shown to reduce the risk of relapse

• All ASA preparations are effective for maintaining remission.

• Steroids are ineffective for maintenance of remission.

• Immunosuppressants (AZA/6-MP, etc.) are used in steroid-dependent patients or patients who are difficult

to wean from steroids.

INDICATION OF SURGERY

• Indications for urgent surgery in patients with ulcerative colitis include (1) toxic megacolon refractory to medical management, (2) fulminant attack refractory to medical management, and (3) uncontrolled colonic bleeding.

• Indications for elective surgery in ulcerative colitis include (1) long-term steroid dependence, (2) dysplasia or adenocarcinoma found on screening biopsy,

LONG TERM MONITORING • Patients with extensive colitis or left-sided colitis with negative

findings on screening colonoscopy should begin surveillance colonoscopy in 1-2 years. For patients with ulcerative colitis and primary sclerosing cholangitis, screening and subsequent surveillance colonoscopy should begin on an annual basis at the time of onset of primary sclerosing cholangitis.

• Patients with proctosigmoiditis have no increased risk for colorectal cancer compared with the general population. However, these patients should be managed according to the current guidelines on colorectal cancer screening. If high-grade dysplasia or cancer is found, colectomy is performed. The management of low-grade dysplasia is controversial[79] ; however, most experts would recommend colectomy.

PROGNOSIS

• The most common cause of death of patients with ulcerative colitis is toxic megacolon. Colonic adenocarcinoma develops in 3-5% of patients with ulcerative colitis, and the risk increases as the duration of disease increases. The risk of colonic malignancy is higher in cases of pancolitis and in cases in which onset of the disease occurs before the age of 15 years. Benign stricture rarely causes intestinal obstruction.