PHR 927 Block 4 IBD Etiology and Pathophysiology

irritable bowel disease (IBD)

chronic inflammation of the bowel

two types: ulcerative colitis and crohn's disease

ulcerative colitis

(UC)

mucosal inflammatory condition

confined to rectum and colon

crohn's disease

(CD)

transmural inflammatory condition

can affect any part of the GI tract

IBD epidemiology

- most common in USA and Northern Europe

- peak in 2nd - 3rd decade of life

- UC: more frequently in males

- CD: more frequently in women

- higher incidence in Jewish population

- more likely to develop if a relative has IBS

4 theories of IBD cause

1. immunologic

2. infectious: microbial dysbiosis; early exposure to antibiotics

3. genetics: 200+ genes associated with IBS

4. environmental:

- diet: ↓ dietary fiber, red meat, trans-unsaturated far, artificial sweeteners

- breastmilk: ↑ breastmilk ↓ UC development

- hygiene hypothesis: early exposure stimulates diversity and maturation of gut microbiome

- smoking: ↑ smoking ↓ UC development ↑ CD development

- NSAIDs: ↑ NSAIDs ↑ IBD onset (15+ days/month)

UC pathophysiology

- confined to rectum and colon: proctitis and left sided colitis are most common

- affects mucosal and submucosal layers

- fistula, perforation, or obstruction are uncommon

UC complications

local:

- hemorrhoids

- anal fissures

- perirectal abscess

- toxic megacolon

- colorectal carcinoma

- extra-intestinal manifestations

UC clinical features

common features:

- rectal bleeding

may be present:

- abdominal tenderness

rare/ uncommon:

- malaise/ fever

- abdominal pain

UC clinical presentation

1. distal disease: inflammation limited to areas distal to splenic flexure; "left sided disease"

2. extensive disease: inflammation extending proximal to the splenic flexure; majority of colon

3. proctitis: inflammation confined to the rectum

4. proctosigmoiditis: inflammation of the rectum and sigmoid colon

- onset: gradual (weeks to months)

- disease characterized by relapsing and remitting flares of mucosal inflammation

CD pathophysiology

- occurs anywhere in GI tract: mouth to anus

- terminal ileum most common

- transmural inflammatory process with deep ulcers

- fistula, perforation, or obstruction are more common

CD complications

fistulas (perianal, enterocutaneous, enteroenteric, enterovesicular, enterovaginal)

- lower risk of carcinoma than UC

- nutritional deficiencies

- extra-intestinal manifestations

CD clinical features

common:

- malaise/ fever

- rectal bleeding

- abdominal tenderness

- abdominal pain

- fistulas

- aphthous ulcers

CD clinical presentation

S&S:

- malaise and fever

- abdominal pain

- frequent bowel movements

- hematochezia

- fistula

- weight loss and malnutrition

- arthritis

- bone fractures

- thromboembolism

physical exam & labs:

- abdominal mass and tenderness

- perianal fissure or fistula

- increased WBC, ESR, CRP, and fecal calprotectin

extraintestinal manifestations

symptoms affecting organs outside the intestines

- hepatobiliary

- joint arthralgias

- ocular

- dermatologic

- mucotaneous

- hematologic

- coagulation

- pulmonary

- metabolic

UC disease classification

Truelove and Witts: number of stools per day, blood in the stools, temperature, pulse, hemoglobin, and ESR

Mayo Score: from 0-12 , remission - severe disease

CD disease classification

no gold standard

Crohn's Disease Activity Index (CDAI): gauge response to therapy and determine remission

Harvey-Bradshaw Index (HBI): simpler than CDAI, but 93% with CDAI

- <150 to >450

endoscopy

- ileocolonscopy with at least 2 biopsies should be performed in the assessment of patients with IBD

- disease distribution and severity should be documented

- upper endoscopy should only be performed in pts with upper GI signs and symptoms

- video capsule endoscopy may be useful in diagnosis of patients with small bowel CD

imaging studies

radiograph: for pts with concern for toxic megacolon, warranted to assess for colonic dilation

small bowel imaging: performed as initial diagnostic workup for pts with suspected CD

abdominal CT scan: often imaging of choice; thickening is seen in advanced disease

magnetic resonance enterography (MRE): useful in diagnosing chronic IBD; expensive and time consuming

transabdominal ultrasound: most sensitive in the ileum and sigmoid/ descending colon

- new, noninvasive, cheaper, well tolerated; operator dependent, may fail to detect superficial mucosal disease

routine laboratory investigation

complete blood count: anemia, elevated platelets

serum C-reactive protein (CRP): acute-phase reactant produced by the liver; short half life

erythrocyte sedimentation rate (ESR): non-specific measure of inflammation

stool studies for fecal pathogens: C. diff, viruses, parasites

fecal calprotectin and fecal lactoferrin

dehydration: electrolytes

malnutrition

monitoring disease activity

fecal markers: fecal calprotectin (>160 - predicts relapse)

serum CRP: monitor response in pts on infliximab

CTE and MRE: useful for pts with small bowel disease

mucosal healing: determined by endoscopy

- absence of ulceration, sustained remission, decreased surgery and hospitalization

serologic markers of IBD

routine use of serologic markers for the diagnosis or prognosis of IBD is not indicated

perinuclear antineutrophil cytoplasmic antibody (pANCA)

- positivity in up to 70% of pts with UC

- no relationship between pANCA and disease site/ activity/ treatment/ surgery

genetic testing

not indicated to establish diagnosis of IBD