Inflammatory%20bowel%20disease Diagnosis

• IBD is confirmed by clinical evaluation and a combination of biochemical, endoscopic, radiologic, histologic and/or nuclear medicine-based investigations
• Specific diagnosis of UC or CD is not determined in about 5% of patients because they have features of both conditions; this is termed as IBD type unclassified (IBDU)

• Complete patient history should include:
  
  • Recent travel history, intolerances to food, smoking history, sexual history, medication (including use of NSAIDs and antibiotics) and vaccination history, past medical history [eg previous appendectomy, tuberculosis (TB), intestinal infection], family history
• Onset and duration of symptoms
• Stool frequency, consistency, urgency
• Presence of extraintestinal manifestations (eg arthritis, osteoporosis, fractures, inflammatory ocular symptoms, thromboembolic symptoms, primary sclerosing cholangitis (PSC), secondary amyloidosis, erythema nodosum, pyoderma gangrenosum)
• Presence of mood disorders

• General well-being, pulse rate, blood pressure, temperature, body mass index (BMI), hydration/nutritional status, check for anemia
• Inspection of eyes, mouth, skin and joints for extraintestinal involvement
• Abdominal tenderness or distension, palpable mass, perianal exam (eg presence of fissures and fistulas)
• Digital rectal exam for anal strictures, mass

• Complete blood count (CBC), liver function test (LFT), serum albumin, ferritin, calcium, magnesium, vitamin B12 level
• Electrolytes - as indicators of decreased absorption
• Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
  • Elevated CRP with increased ESR, anemia and hypoalbuminemia are used as predictive biomarkers to assess the need for colectomy in patients with acute severe colitis
• Routine stool exam including checking for occult blood or fecal leukocyte and stool culture
• Stool microbiologic testing for infectious diarrhea including Clostridioides difficile toxin, cytomegalovirus (CMV)
  
  • Should be considered in severe or refractory colitis
• Fecal calprotectin to detect intestinal inflammation
  • A neutrophil-derived protein and is the most sensitive marker of intestinal inflammation in IBD
  • Aids in differentiating IBD from irritable bowel syndrome 
  • Can be used for diagnosis and assessment of disease severity in UC and has good correlation with endoscopic indices, relapse and response to treatment
    • May be used for monitoring disease activity of IBD patients on therapy
    • May be used as a marker for relapse in patients with inactive IBD
• HIV and TB testing for high-risk population

Serologic Markers

• Occasionally helpful in identifying patients who are at higher risk for complications and in selected patients in whom no other pathologic or clinical feature differentiates between CD from UC
• UC: Perinuclear antineutrophil cytoplasmic antibodies (pANCAs)
• CD: Anti-Saccharomyces cerevisiae antibodies (ASCA), CBir 1 (an anti-flagellin antibody)
• Not sufficiently sensitive nor specific to be used as screening or diagnostic tool

Endoscopy

• May differentiate CD from UC in >85% of patients if used in conjunction with other diagnostic modalities
• Used to assess disease extent and activity, to monitor response to therapy, and for surveillance of dysplasia or neoplasia
• Upper GI endoscopy is recommended for patients with CD with upper GI symptoms (nausea and vomiting, dyspepsia), but not for asymptomatic, newly diagnosed, adult IBD patients
  • Findings include aphthous ulcers, superficial erosions, late-stage stricture development, and cobblestoning of the mucosa
• Biopsy is an important part of endoscopic exam
  
  • Differentiates CD from UC and excludes presence of other causes of colitis
  • May help in establishing the extent of inflammation which aids in determining the appropriate therapy and disease prognosis
  • Recommended even in the absence of macroscopic change (normal-looking mucosa)

Colonoscopy

• Ileocolonoscopy with biopsies from inflamed and uninflamed segments is recommended for suspected IBD to establish diagnosis
  • Recommended to confirm the diagnosis of UC, and to determine the extent and severity of inflammation
  • Recommended for patients with unexplained perianal fistula and suspicion of CD to assess mucosal inflammation in the ileum or colon
• Should not be done in patients with acute severe colitis or suspected of toxic megacolon due to increased risk of perforation
• CD: Findings of segmental or discontinuous colitis or patchiness, presence of stricture and fistulae, rectal sparing, involvement of the terminal ileum and right-sided colon, and anal or perianal disease
  
  • Presence of ulcers (discrete, aphthous or serpiginous), cobblestoning of mucosa, granulomata
• UC: Findings of granularity, friability, ulceration of the rectal mucosa and the vascular pattern is lost, diffuse superficial inflammation, erosions, and ulcers
  
  • These changes, seen endoscopically and histologically, usually involves the distal rectum
  • Characterized by continuous and confluent colonic involvement with clear demarcation of inflammation and rectal involvement
• Colonoscopy with ileoscopy may help distinguish true CD ileitis from backwash ileitis
• At least 2 biopsies from 5 sites, including distal ileum and rectum, is recommended
• Use of chromoendoscopy during colonoscopy is recommended in patients with high risk for colorectal cancer (CRC) (eg patients with history of dysplasia or with PSC)

Flexible Sigmoidoscopy

• Performed when colonoscopy is considered high risk (eg fulminant colitis) or where there is higher risk of bowel perforation
• In patients diagnosed with UC, it helps in assessing disease activity and in evaluating other causes of colitis during disease exacerbations
• Proctosigmoidoscopy or ileocolonoscopy is recommended in all patients with perianal CD to assess extent of disease, severity of luminal inflammation, presence of internal openings, and to exclude complications eg stricture and cancer
• Recommended to confirm the diagnosis of severe colitis and exclude infection
  • Severe colitis is demonstrated as hemorrhagic mucosa with deep ulceration, mucosal detachment on the edge of the ulcerations, and well-like ulceration

Capsule Endoscopy

• Small bowel capsule endoscopy (SBCE) allows for direct visualization of the small intestinal mucosa 
• A less invasive technique in diagnosing CD when ileoscopy and small bowel follow-through (SBFT) are negative or unsuccessful
  • Presence of ≥3 small intestine ulcers is highly suggestive of CD, provided patient has not been taking NSAIDs for at least 1 month
• May also be considered in patients with unclassified IBD at diagnosis
• Contraindicated in CD patients with known or suspected high-grade strictures, swallowing disorders and GI obstruction
• Does not allow tissue sampling but may identify a site for directed biopsy to obtain tissue samples for diagnosis
• Major concern on capsule retention limits its use

Balloon-assisted Enteroscopy

• Allows direct mucosal visualization of the entire small bowel, may be used for diagnostic evaluation and endoscopic intervention throughout the small bowel
• Advantages include the possibility of taking biopsies, conduct therapeutic intervention throughout the small bowel and interventions to manage bleeding
• Disadvantages include the need for patient sedation and examination is time-consuming
• Endoscopic balloon dilatation is an option for CD patients with primary intestinal strictures or anastomotic strictures

Endoscopic Ultrasonography (Rigid Scope or with Flexible Endoscopes)

• It can accurately assess and characterize Crohn’s perianal fistula
• Used in assessing disease activity of colitis and transmural disease

Radiologic Studies

• Complements endoscopic techniques in the diagnosis of IBD

Abdominal Radiography

• Excludes colonic dilatation, helps assess disease extent in UC or identify proximal constipation
• In CD, it shows mass in the right iliac fossa or small bowel dilatation, obstruction or perforation

Barium Contrast Examinations

• Eg SBFT, small bowel enteroclysis (SBE)
• Typically inferior to colonoscopy
• Shows luminal narrowing with ulcerations, loop adhesions/separations, and circular fold thickening and alterations
• SBE is 95% sensitive and 96.5% specific for small bowel diseases especially for early mucosal lesions
• SBFT is safer and better in detecting gastroduodenal abnormalities as compared to SBE (67-72% accuracy in detecting inflammation)
• Limitations: Extraluminal extensions, bowel wall complications of CD and radiation exposure

Ultrasound

• Excludes colonic dilatation, helps assess disease extent in UC and identify proximal constipation
• A noninvasive, sensitive way of identifying thickened small bowel loops in CD
  • Intestinal ultrasound (IUS) is recommended for newly diagnosed CD patients to assess the small bowel
• 79% sensitive, 93% specific for stenosis; 71-74% sensitive, 95-96% specific for fistula; 84% sensitive, 93% specific for abscess
• May also identify abscess and free fluid in peritoneum
• Also used as an imaging guide during procedures
• Advantages of IUS: Non-invasive, provides rapid evaluation of bowel wall thickness, direct visualization of bowel vascularization and motility, and does not use ionizing radiation
• A prospective trial has shown good concordance between ultrasound and magnetic resonance (MR) enterography for disease location and activity, and fewer technical difficulties with IUS
• Limitations: Limited access to the proximal ileum and jejunum, transverse colon and rectum

Computed Tomography (CT)

• The gold standard for the detection of extraluminal complications particularly abscess formation
  
  • UC: May show marked bowel wall thickening, although this finding is nonspecific
• Can be used for newly diagnosed CD patients to assess the small bowel
  • Can establish disease extent and activity based on wall thickness and increased intravenous (IV) contrast enhancement
• A better imaging tool against peristalsis and motion because of its rapid pacing
  
  • 92% sensitive, 100% specific for stenosis; 89% sensitive for inflammation; 70% sensitive, 97% specific for fistula; 85% sensitive, 95% specific for abscess
• Produces results faster and is readily available as compared to MRI
• Limitation: May require luminal distention and application of contrast media; carries a potential risk for radiation-induced malignancy

Magnetic Resonance Imaging (MRI)

• A good imaging tool that limits motion and peristalsis due to its fast sequences
• 89% sensitive, 94% specific for stenosis; 83% sensitive for inflammation; 76% sensitive, 96% specific for fistula; 86-100% sensitive, 93-100% specific for abscess; 76% sensitive, 96% specific for abscess/fistula/inflammation infiltrates in CD
• Can be used for newly diagnosed CD patients to assess the small bowel
  • Can establish disease extent and activity based on wall thickness and increased IV contrast enhancement
• Most accurate imaging modality to diagnose and classify perianal CD and is considered as the 1st-line test 
• Provides information about disease activity, detects extraluminal findings and wall complications, and helps distinguish between inflammatory and fibrotic stricturing
  
  • Preferred over CT to minimize cumulative risks of radiation
• Limitation: Requires administration of contrast media

Nuclear Medicine/Scintigraphy

• A technique that can identify disease extension and activity
• Has lower radiation exposure; recommended for children
• WBC scintigraphy is more sensitive for screening of IBD because of the application of radiolabeled leukocytes
  • There is not enough evidence to support the use of FDG-PET in post-treatment IBD patients

• Should attempt to define the type of IBD, mention coexistent diagnosis or complications, and determine presence of dysplasia and its grade
• UC: Mucosal separation, distortion and atrophy of crypts; acute and chronic inflammatory cells in the lamina propria, preferential homing of neutrophils to the crypt epithelium, increased number of plasma cells near crypt base
  • Focal or diffuse basal plasmacytosis is the earliest feature with the highest predictive value for diagnosis
  • Widespread mucosal or crypt architectural distortion, mucosal atrophy, and an irregular or villous mucosal surface are features that appear 4 weeks after presentation
• CD: Granulomas and focal crypt architectural abnormalities with focal or patchy chronic inflammation (defined as the presence of lymphocytes and plasma), or mucin preservation at active sites
  • Diagnosis is made when at least 3 histological features of CD are present on surgical samples in the absence of granulomas, or when an epitheloid granuloma is present with one other feature:
    • Segmental crypt architectural abnormalities and mucin depletion
    • Mucin preservation at active sites
    • Focal chronic inflammation without crypt atrophy

Severity Assessment of Ulcerative Colitis

• Clinical severity and anatomical extent of an acute attack of UC determines the therapeutic approach
• Disease severity can be assessed using several disease activity indices (eg Truelove and Witts criteria, Mayo Clinic index, Sutherland index)

Endoscopic Scoring

• Used for standardization of care to guide treatment decisions with the aim of achieving mucosal healing

Severity Assessment

Histological Scoring

• Active disease: Presence of neutrophils within the crypt epithelium and crypt lumen, and erosions and ulcers
• Mucosal healing: Partial resolution of the crypt architectural distortion and of the inflammatory infiltrate, but mucosa will still show some features of sustained damage (decreased crypt density with branching, shortening of crypts), decrease in basal plasmacytosis
• Histological remission: Evidence of normalization of bowel mucosa

Severity Assessment of Crohn's Disease

• CD severity is generally more difficult to determine than UC
• Crohn’s Disease Activity Index (CDAI), the Harvey-Bradshaw Index (HBI) and Perianal Disease Activity Index (PDAI) are commonly used systems in describing disease severity
• Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are validated and reproducible scoring systems for measuring luminal endoscopic activity

Mild to Moderate Disease (Corresponds to CDAI 150-220)

• Patient is ambulatory
• Able to tolerate oral alimentation with:
  
  • No manifestation of dehydration
  • No sign of toxicity (high fever, rigors, prostration)
  • No abdominal tenderness or painful mass
  • No intestinal obstruction
  • <10% weight loss

Moderate to Severe Disease (Corresponds to CDAI 220-450)

• Fever
• Significant weight loss (>10%)
• Abdominal pain or tenderness
• Intermittent nausea or vomiting without obstructive findings
• Significant anemia
• May also refer to patients who failed to respond to treatment for mild to moderate disease

Severe to Fulminant Disease (Corresponds to CDAI >450)

• High fever
• Persistent vomiting
• Evidence of intestinal obstruction
• Rebound tenderness or involuntary guarding
• Cachexia
• Evidence of an abscess
• Also describes patients with persistent symptoms despite outpatient treatment of corticosteroids or biologic agents

• Anatomical extent of UC is assessed endoscopically
• Defined by the maximal macroscopic extent during colonoscopy
• Determines treatment modality whether oral and/or topical, and determines onset and frequency of surveillance

Montreal Classification of Extent of Ulcerative Colitis

Proctitis

• Involvement is limited to the rectum (proximal extent of inflammation is distal to the rectosigmoid junction)
• Same risk of developing CRC with the population
• 10-year colectomy rate of 5%

Left-sided (Distal) Colitis

• Limited to below the splenic flexure and therefore may be reached by topical therapy
• Intermediate risk of developing CRC but risk increases as duration of disease increases
• 10-year colectomy rate of 8%

Extensive Colitis (Pancolitis)

• Colitis that extends proximal to the splenic flexure, including pancolitis and therefore requires systemic therapy
• Highest risk of developing CRC
• 10-year colectomy rate of 19%