Inflammatory bowel diseases (I.B.D)

IBD TWO MAIN FORMS: ULCERATIVE COLITIS- AFFECTS LARGE BOWEL ONLY CROHN’S DISEASE- AFFECTS ANY PART OF GIT

Epidemiology of IBD Ulcerative colitis Crohn’s disease 11/100 000 Incidence (US) 11/100 000 7/100 000 Age of onset 15-30 & 60-80 Male:female ratio 1:1 1,1-1,8:1 Smoking May prevent disease May cause disease Oral contraceptive No increased risk Relative risk 1,9 Appendectomy Not protective Protective Monozygotic twins 8% concordance 67% concordance

High Medium Low

Epidemiology UC Highest incidence in Europe, United Kingdom, North America Incidence per person-years 2.2–14.3/100,000 Age of onset 15–30 & 60–80 Male:female ratio 1:1 Smoking May prevent disease Oral contraceptives No increased risk Appendectomy Protective Monozygotic twins 6% concordance Dizygotic twins 0% concordance

Epidemiology Crohn,s disease Incidence: 7/100 000 pop/yr World wide distribution but more common in the West. The incidence is lower in non-white races. Females are affected more than males 1.2:1 Epidemiology Jews are more affected than non-Jews Bimodal age distribution: 20-40 yrs/60-80 yrs The incidence is rising Prevalence: 100/100 000 pop/yr

Etiology Genetic Defective immune regulation Exogenous factors

Etiology & Pathogenesis The aetiology of IBD disease is unknown. There are many proposed pathogenic mechanisms, some of which are represented in this diagram. As there is no one cause, it is likely that IBD disease is an outcome of interactions between genetic predisposition, environmental factors and the subsequent reaction of the host immune system. Genetic susceptibility Environmental factors Host Immune Response IBD

Genetic: IBD patients have disease-associated foci on chromosome 16, 12,7,5,3,1 (gene NOD-2) Ulcerative colitis express HLA DR2 and CD express DR5 DQ1, DRB0301. IBD patients with HLA DRB10130, have extensive disease and extraintestinal manifestation such as : mouth ulcers,arthritis,uveitis

Immune dysregulation in IBD NORMAL IBD normal IBD Antigen and flora Antigen and flora Dysregulation ? CD4+ T Inhibitory cytokines IL-10,TGF-b CD -TH2 CD-TH1 IL-4,IL5,IL13 ING- ,TNF Inflammatory cytokines Oral tolerance Ulcerative colitis Crohn,s colitis

Pathology Ulcerative colitis : (1)Is a mucosal disease of colon (2) 40-50% involve rectum ,30-40% rectosigmoid ,20% pancolitis (3) Backwash ileitis :10-2%% (4) Mucosa is erythematous , hemorrhage ,ulcerations , pseudopolyps

Pathology( crohn,s): Affect any part of GI from mouth to anus 30-40% small bowel 40-55% small and large bowel 15-25% alone colitis,” cobblestone” 90% terminal ileum is involved is a transmural disease with skip area , rectum is spared ,preanal lesion like fistula ,fissures , abcesses,anal stenosis in see in 30%.

Normal colon

ULCERATIVE COLITIS CONTINUOUS INVOLVEMENT

CROHNS vs PM COLITIS

Clinical: Intestinal Extraintestinal

Ulcerative colitis

Disease distribution Ulcerative Colitis Left sided cloitis Proctosigmoiditis Proctitis

Disease distribution The disease typically is most severe distally and progressively less severe more proximally. In contrast to Crohn's disease, continuous and symmetrical involvement is the hallmark of UC, with sharp transition between diseased and uninvolved segments of bowel

Clinical Features diarrhea rectal bleeding passage of mucus tenesmus urgency abdominal pain

The onset of UC typically is slow and insidious. Clinical Features The onset of UC typically is slow and insidious. Symptoms have usually been present for weeks or months by the time the patient seeks medical attention. The median interval between the onset of symptoms and diagnosis of UC is approximately 9 months. Some patients with UC may present much more acutely, with symptoms mimicking infectious colitis.

Intestinal symptoms of UC Diarrhea, rectal bleeding ,tenesmus, passage of mucus crampy pain, incomplete evacuation. Intestinal complications : bleeding, toxic colon, perforations , obstructions

Intestinal symptoms of CD : Ileocolitis : diarrhea and chronic RLQ pain Jejunoileitis :malabsorption Colitis :diarrhea, low grade fever,pain, some times hematochezia Gastroduodenal : G.O.O Intestinal complications :fistula, perforation, intestinal obstruction, hemorrhage, preanal diseases.

Extraintestinal Manifestations of IBD Skin Erythema nodosum Pyoderma gangrenosum Joints Peripheral arthritis Sacroileitis Ankylosing spondylitis Eye Uveitis Episcleritis Iritis Hepatobiliary complications Gallstones PSC Renal complications Nephrolithiasis Recurrent UTIs

Extraintestinal complications of I.B.D Oral : Dermatologic : (1)Erythema nodosum, CD, 15% (2)Pyoderma gangrenosum , UC ,1-12%

Extraintestinal complications of I.B.D Rheumatologic : (1)Peripheral arthritis, CD,15-20% (2)Ankylosing spondylitis : CD, 10%, and 2/3 have positive test fir HLA-B27,no relation to activity (3)Sacroiliitis :CD=UC, No relation to activity

Extraintestinal complications of I.B.D Ocular :1-10% (1)Conjuntivitis (2)Anterior uveitis/iritis (3)Episcleritis

Extraintestinal complications of I.B.D Hepatobiliary: (1)Hepatic steatosis :50% (2)Cholelithiasis : CD>UC is seen in 10-35% patients with ileitis (3) Primary sclerosing cholangitis :1-5%of I.B.D patients have PSC 50%-75 of patients with PSC have I.B.D (4)Peicholangitis :

Extraintestinal complications of I.B.D Urologic : (1)Calculi :CD, 10-20% (2)Ureteral obstruction (3)fistula

Lab in IBD In ESR,CRP, Hb PANCA :Is positive in 5% population, 5-10% in first degree relatives 5-10% in CD , 60-70% in UC ASCA : 5% Population ,10-15% in UC, 60-70% in CD ANCA positivity is more associated with pancolitis, early surgery, pouchitis, PSC.

Medical treatment (1)Sulfasalazine

Adverse Effects of Sulfasazine Dose related nausea vomiting anorexia folate mal-ab. Headache alopecia Not dose related skin rash hemolytic anemia agrannulocytosis fibrosing alveolitis hepatitis male infertility colitis

Newer therapy: (2) 5-ASA a-azo-band : olsalazine b-5-ASA dimer(resin) :delayed release, pH dependent , Asacol c: sustained released: ethylcellulose microgranules , PENTASA

Treatment (continuous): (3)Glucocorticoids : a-oral b-Iv c-suppository and enema (4) Antibiotics : metronidazole, ciprofloxacin. fistula , preanal lesions (5)Azthioprine,,methotrexate,cyclosporine(iv dose2-4mg/kg 82% effective in UC refractory to therapy ) 6-MP (6)Anti-TNF antibody (infliximab) : dose 5mg/kg ,65% of refractory CD respond,repeat every 8 weeks.

Treatment protocol is based in two factors: Colonic involvement extent DAI

Disease distribution Ulcerative Colitis Left sided cloitis Proctosigmoiditis Proctitis

FACTORS MODIFYING RISK OF COLITIS-ASSOCIATED CANCER Cancer risk in IBD: 41. FACTORS MODIFYING RISK OF COLITIS-ASSOCIATED CANCER It has long been recognized that long duration and wide anatomical extent of colitis are the two principal factors contributing to increased risk of colitis-associated colorectal cancer. More recently, a positive family history of colorectal cancer has been identified as an additive risk factor, much as it is in the non-colitis population. The co-existence of colitis with primary sclerosing cholangitis also sharply increases the likelihood of dysplasia and carcinoma of the colon. Although it is not entirely clear whether the reasons for this observation are primarily biological or artifactual, the fact remains that colorectal cancer surveillance needs to start soon after the diagnosis of PSC-associated colitis. (See Fig. 38) On the other side of the coin, there is also some evidence suggesting that aminosalicylate treatment, folate supplementation, and “tight” medical control of the inflammatory process might lower the long-term risks of colorectal cancer in ulcerative colitis. • Shetty K, Rybicki L, Brzezinski A et al. The risk of cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1999;94:1643-9 • Itzkowitz SH. Inflammatory bowel disease and cancer. Gastroenterol Clin North Am 1997;26:129-39. • Askling J, Dickman PW, Karlen P et al. Family history as a risk factor for colorectal cancer in IBD. Gastroenterology 2001;120:1356-62. Primary sclerosing cholangitis Family history of colorectal cancer pseudopolyp

Cancer in I.B.D Sporadic colonic cancer (SCC) arise from adenomatous polyp; colitis associated colonic cancer(CACs ) arise from flat dysplasia or dysplasia-associated lesion or mass (DALM) Multiple synchronous cancers occurs in3-5% SCC and in 12% CAC Mean age SCC is 60 and CAC 30 years SCC exhibits a left- sided predominance ,CAC distribute uniformly Mucinous and anaplastic cancers are more common in CAC than SCS

Inflammatory bowel diseases & pregnancy Patients with quiescent UC and CD have normal fertility rates With increased activity patients have chance of abortion , stillbirths and developmental defects, but not due to medications Antibiotics like ampicillin, cephalosporin,ormetronidazole for short courses are safe Methotrexate and ciprofloxacin are contraindicated Sulfasalazine , 5-ASA and Glucocorticoids are safe

Indications for surgery: Ulcerative colitis Crohn,s disease Intractable disease Fulminant disease Toxic megacolon Colonic perforation Massive colonic hemorrhage Extracolonic disease Colonic obstruction Colonic cancer CD of small intestine: Stricture,obstruction,fistula Refractory to medical therapy Abscess CD of colon and rectum: Intractable Preanal disease,fistula, obstruction refractory to therapy cancer