View source for Inflammatory bowel disease

__NOTOC__
{{Inflammatory bowel disease}}
{{CMG}} ; {{AE}} {{ADG}} ; {{OS}}
{{SK}} IBD ; 
{{Infobox medical condition

| name = Inflammatory bowel disease

| field = Gastroenterology

| synonyms = IBD

| symptoms = Abdominal pain, chronic diarrhea, rectal bleeding, weight loss, fatigue, fever, anemia

| onset = Variable

| duration = Chronic, relapsing-remitting

| types = Crohn disease, ulcerative colitis, IBD-unclassified

| causes = Dysregulated immune response to intestinal microbiota in genetically susceptible individuals with environmental contributions

| diagnosis = Clinical assessment, inflammatory biomarkers, fecal calprotectin, ileocolonoscopy with histology, cross-sectional imaging

| treatment = Treat-to-target therapy using anti-inflammatory agents, immunomodulators, biologics, and small molecules

| frequency = Increasing worldwide prevalence

}}

'''Inflammatory bowel disease (IBD)''' is a group of chronic immune-mediated inflammatory disorders of the gastrointestinal tract characterized by periods of inflammatory activity and remission.

The major disease entities include:

* '''Crohn disease (CD).'''
* '''Ulcerative colitis (UC).'''
* '''IBD-unclassified (IBDU).'''

IBD is a systemic inflammatory disorder with intestinal and extraintestinal manifestations. Inflammation may involve the joints, eyes, skin, and hepatobiliary system.

== Disease entities ==

=== Ulcerative colitis ===

Ulcerative colitis is a chronic inflammatory disorder limited primarily to the colon.

Characteristics:

* Continuous inflammation beginning in the rectum and extending proximally.
* Primarily mucosal inflammation.
* Bloody diarrhea and fecal urgency are common.
* Longstanding colonic inflammation increases colorectal neoplasia risk.

=== Crohn disease ===

Crohn disease may affect any portion of the gastrointestinal tract from mouth to anus.

Characteristics:

* Segmental "skip" lesions.
* Transmural inflammation.
* Strictures, fistulas, and abscess formation.
* Noncaseating granulomas may occur.

Disease behavior is categorized as:

* Inflammatory.
* Stricturing.
* Penetrating.

=== IBD-unclassified ===

IBD-unclassified describes patients with clinical, endoscopic, histologic, and radiologic findings that do not allow definitive classification as Crohn disease or ulcerative colitis.

Classification may change over time with longitudinal follow-up.

== Epidemiology and disease burden ==

IBD prevalence continues to increase globally due to:

* Improved survival.
* Accumulation of chronic disease burden.
* Increasing incidence in newly industrialized regions.

Historically high-incidence Western countries show stabilization or decline in incidence, while prevalence continues to rise.

== Clinical presentation ==

Clinical manifestations depend on:

* Disease location.
* Inflammatory activity.
* Presence of complications.

Common symptoms include:

* Abdominal pain.
* Chronic diarrhea.
* Nocturnal diarrhea.
* Rectal bleeding.
* Mucus passage.
* Weight loss.
* Fatigue.
* Fever.
* Anemia.

Features suggesting Crohn disease complications:

* Postprandial abdominal pain.
* Vomiting.
* Abdominal distension.
* Obstructive symptoms.

Children and adolescents may present with:

* Growth impairment.
* Delayed puberty.
* Nutritional deficiencies.

== Extraintestinal manifestations ==

Extraintestinal manifestations may occur independently of intestinal disease activity.

=== Musculoskeletal ===

* Peripheral arthritis.
* Axial spondyloarthritis.
* Sacroiliitis.

=== Ocular ===

* Episcleritis.
* Uveitis.

=== Dermatologic ===

* Erythema nodosum.
* Pyoderma gangrenosum.

=== Hepatobiliary ===

* Primary sclerosing cholangitis (PSC).

== Diagnosis overview ==

Diagnosis requires integration of:

* Clinical history.
* Physical examination.
* Laboratory inflammatory markers.
* Stool biomarkers.
* Endoscopy with histology.
* Cross-sectional imaging when indicated.

No single test independently establishes the diagnosis.

Fecal calprotectin should be interpreted according to clinical context and pretest probability.

== Biomarker monitoring ==

=== Fecal calprotectin ===

Fecal calprotectin is a neutrophil-derived stool biomarker used to assess intestinal inflammation.

Clinical applications include:

* Differentiating IBD from functional gastrointestinal disorders.
* Monitoring inflammatory activity.
* Supporting treatment decisions.

The AGA framework is based on clinical probability.

{| class="wikitable"
! Clinical scenario !! Threshold !! Interpretation !! Action
|-
| Symptomatic remission with low probability of inflammation || Approximately ≤150 µg/g || Suggests absence of active inflammation || Avoid routine endoscopy
|-
| Moderate-to-severe symptoms with high probability || >150–250 µg/g || Supports active inflammation || Treatment decisions may proceed without routine endoscopy
|-
| Mild symptoms with intermediate probability || Any cutoff || Accuracy insufficient || Perform endoscopy
|}

In established ulcerative colitis for detection of Mayo endoscopic subscore 2–3:

* 50 ± 50 µg/g:
** Sensitivity approximately 78%.
** Specificity approximately 57%.

* 150 ± 50 µg/g:
** Sensitivity approximately 71%.
** Specificity approximately 69%.

* 250 ± 50 µg/g:
** Sensitivity approximately 67%.
** Specificity approximately 73%.

ACG guideline interpretation:

* Pooled sensitivity for endoscopic inflammation: approximately 87%.
* Pooled specificity: approximately 77%.
* Fecal calprotectin around 321 µg/g during clinical remission predicts relapse risk at 6 and 12 months.

A normal fecal calprotectin does not exclude active disease when clinical suspicion remains high.

== Treat-to-target strategy ==

Symptoms correlate poorly with inflammatory burden.

Approximately:

* 50% of asymptomatic patients with Crohn disease.
* 15% of asymptomatic patients with ulcerative colitis.

may have ongoing objective inflammation.

Treatment decisions should integrate:

* Symptoms.
* CRP.
* Fecal calprotectin.
* Endoscopy.
* Imaging when appropriate.
== STRIDE-II treatment targets ==

The STRIDE-II framework defines treatment targets according to time horizon.

=== Immediate targets ===

* Clinical response.
* Improvement in symptoms.

=== Short- to intermediate-term targets ===

* Clinical remission.
* Normalization of CRP when previously elevated.

=== Intermediate targets ===

* Reduction in inflammatory biomarkers.
* Fecal calprotectin reduction toward approximately '''100–250 µg/g'''.
* Endoscopic response in Crohn disease.

=== Long-term targets ===

* Endoscopic healing.
* Absence of disability.
* Restoration of quality of life.
* Normal growth in pediatric patients.

Additional prognostic markers:

* Transmural healing in Crohn disease.
* Histologic improvement in ulcerative colitis.

These provide prognostic information but are not mandatory formal STRIDE-II targets.

=== Endoscopic definitions ===

==== Crohn disease ====

Endoscopic response:

* >50% decrease in SES-CD or CDEIS.

Endoscopic remission:

* SES-CD ≤2.
* CDEIS ≤3 according to validated definitions.

==== Ulcerative colitis ====

Endoscopic healing refers to resolution of visible inflammatory mucosal lesions.

STRIDE-II defines endoscopic remission as:

* Mayo Endoscopic Score (MES) 0.
* UCEIS ≤1.

Endoscopic response:

* Reduction in MES by ≥1 point.
* Reduction in UCEIS by ≥2 points.

Endoscopic improvement, commonly reported in trials, generally refers to MES 0 or 1.

== Treat-to-target trial evidence ==

=== CALM trial — biomarker-driven tight control ===

CALM was an open-label phase 3 randomized trial evaluating biomarker-driven escalation compared with symptom-driven management in patients with active Crohn disease.

Eligibility criteria included:

* CDEIS >6.
* CDAI 150–450.
* No previous immunomodulator or biologic exposure.

Tight-control escalation triggers included:

* Fecal calprotectin ≥250 µg/g.
* CRP ≥5 mg/L.
* CDAI ≥150.
* Recent corticosteroid requirement.

The primary endpoint was mucosal healing defined as:

* CDEIS <4.
* Absence of deep ulcerations.

Results:

=== Primary endpoint ===

Mucosal healing:

* Tight control:
** 56/122 patients (46%).

* Clinical management:
** 37/122 patients (30%).

CMH-adjusted risk difference:

* 16.1%.
* 95% CI 3.9–28.3.
* p=0.010.

=== Secondary endpoints ===

Deep remission:

* Risk difference 14.5%.
* 95% CI 2.9–26.0.
* p=0.014.

Biologic remission:

* Risk difference 14.5%.
* 95% CI 4.1–25.0.
* p=0.006.

Treatment-emergent adverse events:

* 86% versus 82%.
* No treatment-related deaths.

Clinical implication:

Biomarker-driven monitoring has randomized evidence supporting improved objective outcomes in early active Crohn disease.

Limitations:

* Open-label design.
* Site-read endoscopy.
* Short follow-up duration.

=== STARDUST trial — endoscopy-driven escalation of ustekinumab ===

STARDUST evaluated endoscopy-driven treat-to-target escalation compared with standard management in Crohn disease patients responding to ustekinumab induction.

Primary endpoint:

* Endoscopic response at week 48.

Results:

Endoscopic response:

* 38% versus 30%.
* Not statistically significant.

Endoscopic remission:

* 11% versus 15%.
* Not statistically significant.

Clinical remission:

* 62% versus 70%.
* Not statistically significant.

Important limitation:

The maintenance strategy included every-12-week ustekinumab dosing, which differs from FDA-approved every-8-week dosing in the United States.

Subgroup findings remain hypothesis-generating.

=== REACT-2 trial — endoscopic versus symptom-based management ===

REACT-2 was a cluster-randomized trial comparing enhanced care targeting ulcer healing with standard symptom-based management.

It was not an early-combination-therapy trial.

Results:

* No significant difference in the primary endpoint.
* No consistent improvement in endoscopic outcomes.

Post hoc analyses suggested possible benefit in selected patients with:

* Elevated CRP.
* Baseline ulceration.

These findings are hypothesis-generating.

=== AGA pooled analysis ===

Pooling STARDUST and REACT-2:

No significant difference was demonstrated between endoscopic targets and symptom-based targets for clinical remission.

Clinical remission:

* 63.2% versus 57.3%.
* RR 1.04.
* 95% CI 0.78–1.39.

== Practical interpretation of treat-to-target evidence ==

Current evidence supports:

* Objective monitoring rather than symptom assessment alone.
* Biomarker-guided escalation in selected Crohn disease populations.
* Endoscopic reassessment when clinically indicated.

However:

* The incremental benefit of mandatory endoscopic escalation over clinical plus biomarker monitoring remains unproven.

== Early effective therapy and risk stratification ==

Treatment intensity should be individualized according to risk of disease progression.

=== High-risk Crohn disease features ===

* Young age at diagnosis.
* Extensive small bowel involvement.
* Deep ulcerations.
* Perianal disease.
* Stricturing phenotype.
* Penetrating phenotype.
* Need for corticosteroids.

Patients with mild, non-progressive disease may not require aggressive escalation.

== Early combination therapy evidence ==

=== PROFILE trial ===

PROFILE evaluated early infliximab plus immunomodulator therapy compared with conventional step-up treatment.

Findings:

Symptomatic remission at 1 year:

* RR 1.12.
* 95% CI 0.98–1.30.
* Not statistically significant.

Steroid-free, surgery-free remission:

* 79% versus 15%.

Clinical interpretation:

The 79% versus 15% finding should not be presented as the primary clinical remission outcome.

=== REACT-1 trial ===

Pragmatic trial evaluating accelerated treatment strategies.

Findings:

* No significant difference in steroid-free remission.
* Lower disease-related adverse events:
** HR 0.73.
** 95% CI 0.62–0.86.

=== AGA meta-analysis ===

Across 3 trials including 2497 patients:

Clinical remission:

* 66.4% versus 60.6%.
* RR 1.18.
* 95% CI 0.96–1.46.

Overall:

* Benefit for steroid-free and endoscopic outcomes is more consistent than benefit for clinical remission alone.

== Therapeutic classes ==

Treatment selection depends on:

* Disease severity.
* Disease location.
* Disease behavior.
* Prior treatment exposure.
* Risk of progression.
* Patient preference and safety considerations.

The therapeutic goal is sustained steroid-free remission with control of objective inflammation.

== 5-aminosalicylates ==

5-aminosalicylates (5-ASA) are primarily used in ulcerative colitis.

Clinical considerations:

* Effective for mild ulcerative colitis induction and maintenance.
* Oral mesalamine is not recommended for induction or maintenance of moderate-to-severe Crohn disease.
* Mesalamine is not recommended as postoperative prophylaxis for Crohn disease.

== Corticosteroids ==

Corticosteroids are induction therapies only.

They should not be used for maintenance because of:

* Osteoporosis.
* Infection risk.
* Hyperglycemia and metabolic complications.
* Adrenal suppression.
* Other cumulative steroid toxicities.

=== Budesonide ===

Controlled ileal-release budesonide:

* Dose: 9 mg daily.
* Used for selected patients with mild-to-moderate ileocecal Crohn disease.
* Induction therapy only.

Steroids should generally be tapered and discontinued within approximately 3 months whenever possible.
== Acute severe ulcerative colitis ==

Acute severe ulcerative colitis (ASUC) is a medical emergency requiring hospitalization, intravenous corticosteroids, close monitoring, and early colorectal surgical involvement.

Approximately 20–30% of hospitalized patients with ASUC eventually require colectomy.

== Initial evaluation and admission bundle ==

Initial assessment should include:

* Stool frequency.
* Rectal bleeding.
* Abdominal pain.
* Fever.
* Signs of systemic toxicity.

Laboratory evaluation:

* Complete blood count.
* C-reactive protein (CRP).
* Electrolytes.
* Albumin.
* Renal function.
* Other inflammatory markers as clinically indicated.

Additional evaluation:

* Stool testing for infectious causes, particularly '''''Clostridioides difficile''''' infection.
* Flexible sigmoidoscopy with biopsies when appropriate.

=== Recommended admission management ===

Management includes:

* '''Intravenous corticosteroids.'''
* '''Pharmacologic venous thromboembolism (VTE) prophylaxis unless contraindicated.'''
* Avoidance of routine broad-spectrum antibiotics in uncomplicated ASUC.
* Avoidance of total parenteral nutrition solely for bowel rest.
* Preference for enteral nutrition when tolerated.

== Corticosteroid induction ==

Common regimens:

* Methylprednisolone approximately 60 mg/day intravenously.
* Hydrocortisone 100 mg intravenously three to four times daily.

Clinical response should be assessed after approximately 3 days.

Failure to improve requires evaluation for:

* Rescue therapy.
* Surgical intervention.

== Predicting corticosteroid failure ==

The Oxford criteria identify patients at increased risk of colectomy.

High-risk criteria:

* Stool frequency >8 bowel movements/day.

OR

* Stool frequency 3–8 bowel movements/day with CRP >45 mg/L.

Patients meeting these criteria require early escalation planning.

== Rescue therapy ==

For corticosteroid-refractory ASUC:

=== Infliximab ===

Advantages:

* Effective rescue therapy.
* Can continue as maintenance therapy.

Infliximab remains one of the best-established rescue therapies, particularly in patients without contraindications to anti-TNF therapy.

=== Cyclosporine ===

Advantages:

* Rapid immunosuppressive effect.
* Alternative rescue option.

Limitations:

* Nephrotoxicity.
* Hypertension.
* Infection risk.
* Drug interactions.

After cyclosporine-induced remission, transition to maintenance therapy is required.

Options include:

* Thiopurines.
* Vedolizumab.
* Other advanced therapies.

=== Tofacitinib and newer rescue strategies ===

Tofacitinib salvage therapy has demonstrated encouraging results in observational studies; however, randomized evidence remains insufficient for routine first-line rescue use in ASUC.

Selection of rescue therapy should consider:

* Prior biologic exposure.
* Comorbidities.
* Safety profile.
* Need for long-term maintenance strategy.

== Cytomegalovirus colitis in ASUC ==

CMV reactivation may occur in a substantial proportion of patients with corticosteroid-refractory severe colitis.

Active CMV infection is associated with severely inflamed mucosa and poorer outcomes.

== Diagnosis ==

Important principles:

* Biopsies obtained from ulcer bases provide the highest diagnostic yield.
* Hematoxylin-eosin staining has limited sensitivity.
* Immunohistochemistry, rapid viral culture, or tissue PCR are preferred diagnostic methods.

== Treatment ==

Treatment options:

* Intravenous ganciclovir followed by oral therapy.
* Typical treatment duration approximately 14 days.
* Valganciclovir in selected patients.

Clinical principles:

* Antiviral therapy has not demonstrated benefit in patients responding to intravenous corticosteroids.
* Colectomy should not be delayed solely to complete antiviral therapy in patients failing medical management.

== Surgical management in ASUC ==

Urgent colectomy is indicated for:

* Perforation.
* Toxic megacolon.
* Massive hemorrhage.
* Progressive clinical deterioration.

Colectomy should be considered when:

* No meaningful improvement occurs after approximately 3–7 days of appropriate medical therapy.
* Rescue therapy fails.

Surgical consultation should occur early during hospitalization rather than after multiple failed medical interventions.

== Venous thromboembolism prevention ==

Patients with IBD have increased risk of venous thromboembolism (VTE), especially during:

* Active inflammation.
* Hospitalization.
* Corticosteroid exposure.

The risk of VTE remains elevated even in patients with active intestinal bleeding.

== Thromboprophylaxis recommendations ==

Pharmacologic thromboprophylaxis should be provided during hospitalization for:

* IBD-related admissions.
* Non-IBD-related admissions in patients with IBD.

Inflammatory rectal bleeding alone should not prevent prophylactic anticoagulation.

Studies have not demonstrated increased:

* Major bleeding.
* Minor bleeding.
* Blood transfusion requirements.

Preferred agents include standard inpatient pharmacologic prophylaxis regimens unless contraindicated.

== Risk reduction strategies ==

Important measures:

* Achieving inflammatory remission.
* Minimizing corticosteroid exposure.
* Smoking cessation.
* Individualized thrombotic risk assessment before JAK inhibitor therapy.

== Preventive care and vaccination ==

Patients with IBD require preventive care according to:

* Age.
* Disease status.
* Medication exposure.
* Immunosuppression intensity.

General principles:

* Inactivated vaccines are safe and do not increase IBD activity.
* Live vaccines should generally be avoided during significant immunosuppression.
* Vaccinations should ideally be completed before immune-modifying therapy when feasible.
* Appropriate IBD therapy should not be delayed solely because vaccination is incomplete.

== Recommended vaccinations ==

Include:

* Annual influenza vaccination.
* COVID-19 vaccination according to recommendations.
* Pneumococcal vaccination when indicated.
* Recombinant zoster vaccine when eligible.

== Herpes zoster vaccination ==

All adults aged ≥19 years receiving or planning to initiate immune-modifying therapy should receive recombinant zoster vaccine (RZV).

Key points:

* RZV is non-live.
* RZV is not associated with increased IBD flare risk.
* It is preferred in immunosuppressed patients.

Risk of herpes zoster is increased with:

* Thiopurines.
* Anti-TNF therapy.
* JAK inhibitors.
* Corticosteroids.

== Other preventive measures ==

Patients receiving immunosuppressive therapy require:

* Bone mineral density assessment after prolonged systemic corticosteroid exposure (≥3 months at ≥7.5 mg prednisone equivalent daily).
* Annual skin examination in patients receiving thiopurines, methotrexate, or anti-TNF therapy.
* Cervical cancer screening according to recommended guidelines, with consideration of increased surveillance in immunosuppressed women.

Before advanced therapies, evaluate for:

* Tuberculosis.
* Hepatitis B.
* Hepatitis C.
* HIV when clinically indicated.

Additional assessment may be required before:

* JAK inhibitors.
* S1P receptor modulators.

== Natural history and surgery ==

Contemporary surgical rates are substantially lower than historical pre-biologic estimates.

{| class="wikitable"
! Time after diagnosis
! Ulcerative colitis
! Crohn disease
|-
| 1 year
| ~2.8%
| ~12.3%
|-
| 5 years
| ~7.0%
| ~18.0%
|-
| 10 years
| ~9.6%
| ~26.2%
|}

The above estimates represent modern all-era pooled estimates rather than historical cohorts.

Earlier pooled estimates across all treatment eras reported:

* Ulcerative colitis:
** 4.0% at 1 year.
** 8.8% at 5 years.
** 13.3% at 10 years.

* Crohn disease:
** 18.7% at 1 year.
** 28.0% at 5 years.
** 39.5% at 10 years.

A genuinely pre-biologic estimate reported approximately 46.6% cumulative Crohn disease surgery by 10 years.

Declining surgery rates likely reflect multiple factors, including:

* Earlier diagnosis.
* Improved monitoring.
* Better multidisciplinary care.
* Modern medical therapy.
* Changes in surgical practice.

Surgery is not curative for Crohn disease.

Following first intestinal resection:

* Approximately 17.7% require a second resection within 5 years.
* Approximately 31.3% require a second resection within 10 years.

== Postoperative Crohn disease ==

Risk factors for postoperative recurrence include:

* Active smoking.
* Penetrating disease.
* Prior intestinal resection.
* Extensive small bowel disease.
* Perianal disease.

=== Low-risk patients ===

Characteristics:

* Nonsmoker.
* No penetrating phenotype.
* No previous resection.

Management:

* Observation may be appropriate.
* Ileocolonoscopy approximately 6 months after surgery.

=== Intermediate-risk patients ===

Management options:

* Thiopurine therapy.
* Thiopurine plus short-course metronidazole.

Escalate therapy when Rutgeerts score is ≥i2b.

=== High-risk patients ===

Examples:

* Previous resection within 10 years.
* Multiple prior resections.
* Active smoking.

Preferred therapy:

* Anti-TNF therapy.
* Consider combination immunomodulator.

Repeat ileocolonoscopy approximately 6 months postoperatively.

=== Rutgeerts score ===

{| class="wikitable"
! Score
! Findings
|-
| i0
| No lesions
|-
| i1
| ≤5 aphthous ulcers
|-
| i2
| >5 aphthous ulcers with normal intervening mucosa or lesions confined to the anastomosis
|-
| i3
| Diffuse aphthous ileitis
|-
| i4
| Diffuse inflammation with large ulcers, severe lesions, or narrowing
|}

=== Key evidence ===

'''POCER'''

* Colonoscopy-guided treatment escalation reduced postoperative endoscopic recurrence.

'''REPREVIO'''

* Early postoperative vedolizumab reduced severe endoscopic recurrence compared with placebo.

Mesalamine is not recommended for postoperative prophylaxis.
== Colorectal cancer surveillance ==

Patients with longstanding colonic inflammatory bowel disease have increased risk of colorectal cancer (CRC).

Surveillance applies to:

* Ulcerative colitis extending beyond the rectum.
* Crohn colitis with substantial colonic involvement.

Average-risk colorectal cancer screening applies to:

* Isolated small bowel Crohn disease.
* Isolated ulcerative proctitis.

== When to begin surveillance ==

Routine surveillance:

* Approximately 8 years after onset of colonic disease.

Patients with primary sclerosing cholangitis (PSC):

* Begin surveillance at the time PSC is diagnosed regardless of IBD duration.

Patients with a first-degree relative diagnosed with colorectal cancer before age 60:

* Begin surveillance 10 years before the relative's age at diagnosis or 8 years after IBD onset, whichever occurs first.

== Surveillance intervals ==

Risk stratification determines surveillance frequency.

High-risk patients:

* Annual colonoscopy.

Intermediate-risk patients:

* Every 2–3 years.

Selected low-risk patients:

* Longer intervals may be appropriate, although many guidelines recommend intervals no longer than 3 years.

== Preferred surveillance technique ==

Preferred approach:

* High-definition colonoscopy with chromoendoscopy and targeted biopsies.

If chromoendoscopy is unavailable:

* High-definition white-light colonoscopy.
* Targeted biopsies.
* Four-quadrant random biopsies approximately every 10 cm.

Surveillance should ideally be performed during remission.

Colonic strictures require careful evaluation because malignancy may coexist.

== Pouchitis and inflammatory pouch disorders ==

Inflammatory disorders of the ileal pouch occur after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).

Diagnosis requires:

* Endoscopic confirmation of inflammation.
* Exclusion of alternative causes.

AGA guidance consists primarily of conditional recommendations based on low-certainty evidence.

== Management ==

=== Intermittent pouchitis ===

Management:

* Antibiotics.

=== Recurrent antibiotic-responsive pouchitis ===

Management:

* Consider probiotics to reduce recurrence.

=== Chronic antibiotic-dependent pouchitis ===

Options include:

* Chronic antibiotics.
* Advanced therapies when long-term antibiotics are undesirable or ineffective.

=== Chronic antibiotic-refractory pouchitis ===

Management:

* Advanced immunosuppressive therapy.
* Corticosteroids may be considered in selected patients.

=== Crohn-like disease of the pouch ===

Management:

* Corticosteroids.
* Advanced biologic or targeted therapy.

=== Cuffitis ===

Initial treatment:

* Topical 5-ASA.
* Topical corticosteroids.

Current evidence has not demonstrated clear superiority of one advanced therapy class over another.

== Pregnancy ==

Women with IBD should ideally conceive while disease is in documented remission.

Active disease is associated with increased:

* Maternal complications.
* Preterm birth.
* Low birth weight.
* Disease-related complications.

== Continue during pregnancy ==

Generally appropriate when clinically indicated:

* 5-ASA agents.
* Sulfasalazine.
* Thiopurines.
* Anti-TNF therapy.
* Vedolizumab.
* Ustekinumab.
* Corticosteroids when necessary.

== Avoid or discontinue ==

Avoid:

* Methotrexate.
* JAK inhibitors.
* S1P receptor modulators.

Methotrexate should be discontinued at least 6 months before conception.

Ozanimod should be discontinued at least 6 months before conception.

Thiopurines and methotrexate should not be newly initiated during pregnancy.

== Practical considerations ==

* Sulfasalazine requires folic acid supplementation.
* Infliximab and adalimumab cross the placenta after approximately 20 weeks.
* Infants exposed to biologics during late pregnancy should avoid live vaccines during the first 6 months of life.
* Certolizumab has minimal placental transfer.
* MRI without gadolinium is preferred over CT when imaging is required.
* Cesarean delivery is recommended for active perianal Crohn disease or previous rectovaginal fistula.

== Anemia and nutritional deficiencies ==

Anemia is one of the most common systemic complications of inflammatory bowel disease.

Iron deficiency and/or iron deficiency anemia occur in up to 90% of patients during the disease course.

Common causes include:

* Chronic intestinal blood loss.
* Active inflammation with impaired iron utilization.
* Reduced dietary intake.
* Malabsorption.
* Previous intestinal surgery.

== Screening ==

Assessment should include:

* Complete blood count.
* Ferritin.
* Transferrin saturation.
* C-reactive protein (CRP).

Monitoring frequency:

* Every 6–12 months during remission or mild disease.
* Approximately every 3 months during active disease.

Ferritin is an acute-phase reactant; therefore, normal or elevated ferritin does not exclude iron deficiency during active inflammation.

Additional nutritional assessment should include:

* Vitamin B12.
* Folate.
* Vitamin D.
* Other micronutrients when clinically indicated.

== Iron replacement ==

Treatment principles:

* Optimize control of intestinal inflammation.
* Correct iron deficiency in all patients with iron deficiency anemia.

Intravenous iron is preferred in:

* Active IBD.
* Hemoglobin <10 g/dL.
* Significant anemia.
* Oral iron intolerance.
* Failure of oral iron therapy.
* Extensive intestinal disease.

Randomized trials demonstrate that intravenous iron is associated with:

* Greater likelihood of hemoglobin increase ≥2 g/dL.
* Lower treatment discontinuation rates than oral iron.

ECCO recommends intravenous iron as first-line therapy for active disease and clinically significant anemia.

== Vitamin B12 deficiency ==

Risk factors include:

* Terminal ileal Crohn disease.
* Ileal resection.
* Extensive ileal involvement.

Management:

* Screen patients with ileal disease or previous ileal resection.
* Replace vitamin B12 when deficiency is identified.

== Folate deficiency ==

Risk factors:

* Poor nutritional intake.
* Malabsorption.
* Methotrexate therapy.

Management:

* Replace folate deficiency.
* Supplement when clinically indicated.

== Vitamin D deficiency and bone health ==

Vitamin D deficiency is particularly common in Crohn disease.

Potential consequences:

* Reduced bone mineral density.
* Osteopenia.
* Osteoporosis.
* Increased fracture risk.

Management:

* Assess vitamin D status in at-risk patients.
* Replace deficiency.
* Minimize corticosteroid exposure whenever possible.

== Perianal Crohn disease ==

Perianal Crohn disease represents an aggressive phenotype associated with significant morbidity.

Evaluation should include:

* Pelvic MRI.
* Examination under anesthesia when appropriate.

== Abscess management ==

'''Drainage of abscess is mandatory before initiation of immunosuppressive therapy.'''

Management may include:

* Surgical drainage.
* Seton placement for complex fistulas.

== Medical therapy ==

Anti-TNF therapy remains the best-established biologic treatment.

Infliximab has the strongest evidence for:

* Fistula closure.
* Durable fistula healing.

Persistent fistulizing disease requires multidisciplinary management involving:

* Gastroenterology.
* Colorectal surgery.
* Radiology.

== Therapeutic drug monitoring ==

Therapeutic drug monitoring (TDM) measures serum drug concentration—usually trough concentration—together with antidrug antibodies.

It is most established for TNFα antagonists.

== Rationale ==

=== Exposure–response relationship ===

Across ACT, PURSUIT, GEMINI, UNIFI, FORTIFY, PREVENT, ADVANCE, and MOTIVATE studies:

* Patients in the lowest drug-concentration quartile achieved clinical remission and endoscopic outcomes nearly identical to placebo.

=== Variability in clearance ===

Drug clearance varies because of:

* Immune-mediated mechanisms:
** Neutralizing antidrug antibodies.

* Nonimmune-mediated mechanisms:
** High inflammatory burden.
** Protein loss.

=== Mechanistic failure ===

Adequate drug exposure may still fail when the targeted inflammatory pathway is not the principal driver of disease.

== Reactive TDM ==

Reactive TDM is performed in patients with:

* Clinical evidence of inflammation.
* Biochemical activity.
* Radiologic inflammation.
* Endoscopic inflammation.

It is supported for:

* Primary nonresponse.
* Secondary loss of response.

{| class="wikitable"
! Drug concentration
! Antidrug antibodies
! Interpretation
! Management
|-
| Low
| Absent or low titer
| Underexposure
| Dose intensification or interval shortening
|-
| Low
| High titer
| Immunogenic failure
| Switch therapy; consider adding immunomodulator
|-
| Adequate
| Any
| Mechanistic failure
| Switch mechanism of action
|}

== Concentration threshold before declaring failure ==

Infliximab or adalimumab should not be considered mechanistically ineffective until trough concentrations of approximately:

'''10–15 µg/mL'''

have been achieved.

Stopping therapy below this threshold risks misclassifying underdosing as treatment failure.

== Thiopurine monitoring ==

Target:

* 6-thioguanine nucleotide concentration of '''230–450 pmol/8 × 10⁸ red blood cells'''.

== Proactive TDM — unresolved ==

Proactive TDM involves routine measurement regardless of disease activity.

Current evidence remains conflicting.

Evidence against routine use:

* Meta-analysis of 9 randomized trials found no improvement in clinical remission.
* Increased therapy escalation occurred without reduction in antidrug antibody formation.

Evidence supporting proactive monitoring:

* Meta-analysis of 8 studies found reduced treatment failure, although evidence was mainly observational.

Expert consensus:

* A modified Delphi panel supported proactive anti-TNF monitoring after induction and at least once during maintenance.

Current society position:

* AGA and ECCO consider proactive TDM a knowledge gap and make no recommendation for or against routine use.

== Practical principles ==

* Reactive TDM is established practice for loss of response and primary nonresponse.
* Proactive TDM should be individualized.
* Do not abandon infliximab or adalimumab below 10–15 µg/mL trough concentrations.
* Drug concentrations should always be interpreted with symptoms, CRP, fecal calprotectin, endoscopy, and imaging.

== Common pitfalls ==

* Treating symptoms without confirming objective inflammatory control.
* Using corticosteroids as maintenance therapy.
* Presenting PROFILE secondary outcomes as the primary remission outcome.
* Describing REACT-2 as an early-combination therapy trial.
* Applying STARDUST every-12-week ustekinumab dosing to U.S. clinical practice.
* Applying all-era pooled surgery estimates as historical pre-biologic cohorts.
* Describing filgotinib as FDA-approved.
* Withholding pharmacologic VTE prophylaxis solely because of inflammatory rectal bleeding.
* Omitting recombinant zoster vaccination before immune-modifying therapy when indicated.
* Delaying colectomy solely to complete antiviral therapy in corticosteroid-refractory CMV colitis.

[[Category:Gastroenterology]]
[[Category:Inflammatory bowel disease]]
[[Category:Crohn disease]]
[[Category:Ulcerative colitis]]
[[Category:Immune-mediated diseases]]

{{Gastroenterology footer}}

==Causes==
While the causes of inflammatory bowel disease is unknown, several possibly interrelated studies have been suggested following causes:

=== Common causes ===

==== Genetic factors ====

Important genetic associations include:

* '''NOD2 variants''' — strongly associated with Crohn disease.
* '''ATG16L1''' and autophagy pathways.
* '''IL-23/Th17 immune axis.'''
== Etiologic framework ==

IBD results from inappropriate immune activation against intestinal microbial communities in genetically susceptible individuals.

=== Environmental contributors ===

Potential contributors include:

* Westernized dietary patterns.
* Smoking.
* Altered microbial diversity.
* Antibiotic exposure.
* Urbanization and industrialization.

==== Environmental factors ====
* Alterations in normal bacterial flora of the intestinal tract is responsible for Crohn's disease.
* [[Tobacco smoking|Smoking]]: Unlike Crohn's disease, ulcerative colitis has a lesser [[prevalence]] in smokers than non-smokers.
* Use of [[NSAID|NSAIDs]]
* Stress
* Red meat consumption 

==== Rare causes ====
* [[Hemolytic-uremic syndrome|Hemolytic uremic syndrome]]
* [[Connective tissue disease]]
* [[Vasculitis]]
* [[Radiation therapy]] to the [[prostate]] or [[Pelvis|pelvic area]]
* Chemical or physical trauma to anorectal area
* [[Amyloidosis]]
* [[Behçet's disease|Behçet syndrome]]
* [[Chronic lymphocytic leukemia]]
* [[Lymphoma]]
* [[Proctocolitis|Lipid proctocolitis]]
* [[Tuberculosis]]
* [[Syphilis]]
* Infection with ''[[Entamoeba histolytica]]'' or ''[[Giardia lamblia]]'', most often seen in patients with [[AIDS|acquired immune deficiency syndrome]].
* Infection with ''[[C difficile]]''

==Classification==
Inflammatory bowel disease consists of Crohn's disease and ulcerative colitis. Microscopic colitis is a related inflammatory colitis characterized by chronic inflammation of the colon.

* Inflammatory bowel disease and related inflammatory colitides
** Crohn's disease
*** Based on region involved
**** Ileocolic Crohn's disease
**** Crohn's ileitis
**** Crohn's colitis
*** Based on disease behavior
**** Stricturing disease
**** Penetrating disease
**** Inflammatory disease
** Ulcerative colitis
*** Based on extent
**** Distal ulcerative colitis
**** Proximal ulcerative colitis
**** Pancolitis
*** Based on severity
**** Mild
**** Moderate
**** Severe
** Microscopic colitis
*** Collagenous colitis
*** Lymphocytic colitis
{{tree list/end}}

==Differential diagnosis==
Inflammatory bowel disease must be differentiated from other diseases that  present with [[abdominal pain]], [[fever]] and [[diarrhea]] which include [[appendicitis]], [[diverticulitis]], [[Whipple's disease]], [[mesenteric ischemia]], [[Tropical sprue]], [[hepatitis]] and [[spontaneous bacterial peritonitis]].

{| align="center"
|-
|
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" |Disease
| colspan="13" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Clinical manifestations'''
! colspan="2" rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" |Diagnosis
! rowspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" |Comments
|-
| colspan="9" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" |'''Symptoms'''
! colspan="4" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" | Signs
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" |Abdominal Pain
! colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" | Fever 
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rigors and chills
! style="background:#4479BA; color: #FFFFFF;" align="center" |Nausea or vomiting
! style="background:#4479BA; color: #FFFFFF;" align="center" |Jaundice 
! style="background:#4479BA; color: #FFFFFF;" align="center" |Constipation
! style="background:#4479BA; color: #FFFFFF;" align="center" |Diarrhea
! style="background:#4479BA; color: #FFFFFF;" align="center" |Weight loss
! style="background:#4479BA; color: #FFFFFF;" align="center" |GI bleeding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Hypo-
tension
! colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" | Guarding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rebound Tenderness
! style="background:#4479BA; color: #FFFFFF;" align="center" |Bowel sounds
! colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" | Lab Findings
! style="background:#4479BA; color: #FFFFFF;" align="center" |Imaging
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Inflammatory bowel disease|'''Inflammatory bowel disease''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal or hyperactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Anti-neutrophil cytoplasmic antibody]] ([[P-ANCA]]) in [[Ulcerative colitis]]
* [[Anti saccharomyces cerevisiae antibodies]] (ASCA) in [[Crohn's disease]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[String sign]] on [[abdominal x-ray]] in [[Crohn's disease]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
Extra intestinal findings:
* [[Uveitis]]
* [[Arthritis]]
|-
| colspan="1" rowspan="1" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Acute appendicitis|'''Acute appendicitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Starts in [[epigastrium]], migrates to RLQ
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in pyogenic appendicitis
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |−
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |−
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in perforated appendicitis
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hypoactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Leukocytosis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Ct scan 
* Ultrasound
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Positive Rovsing sign
* Positive Obturator sign
* Positive Iliopsoas sign
|-
| colspan="1" rowspan="1" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Diverticulitis|'''Acute diverticulitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |LLQ
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |−
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in perforated diverticulitis
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hypoactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Leukocytosis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* CT scan  
* Ultrasound 
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* History of [[constipation]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Whipple's disease|'''Whipple's disease''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |N
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Thrombocytopenia]]
* [[Hypoalbuminemia]]
* [[Small intestinal]] [[biopsy]] for [[Tropheryma whipplei]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Whipple's disease other diagnostic studies|Endoscopy]] is used to confirm diagnosis.
Images used to find complications
*[[Whipple's disease x ray|Chest and joint x-ray]]
*[[Whipple's disease CT|CT]]
*[[Whipple's disease MRI|MRI]]
*[[Whipple's disease ultrasound|Echocardiography]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Extra intestinal findings:
* [[Uveitis]]
* [[Endocarditis]]
* [[Encephalitis]]
* [[Dementia]]
* [[Hepatosplenomegaly]]
* [[Arthritis]]
* [[Ascites]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Toxic megacolon|'''Toxic megacolon''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hypoactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Anemia]]
*[[Leukocytosis]] especially in patients with [[Clostridium difficile infection|''Clostridium difficile'' infection]]
*[[Hypoalbuminemia]]
*[[Metabolic alkalosis]] associated with a poor [[prognosis]]
*[[Metabolic acidosis]] secondary to [[ischemic colitis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |CT and [[Ultrasound]] shows:
*Loss of colonic haustration 
*Hypoechoic and thickened bowel walls with irregular internal margins in the [[sigmoid]] and descending colon
*Prominent dilation of the transverse colon (>6 cm)

* Insignificant dilation of ileal bowel loops (diameter >18 mm) with increased intraluminal gas and fluid
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Tropical sprue|'''Tropical sprue''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |N
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Fat soluble vitamin deficiency
* [[Hypoalbuminemia]]
* Fecal stool test
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Barium studies: 
* Dilation and edema of mucosal folds
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Steatorrhea]]- 10-40 g/day (Normal=5 g/day)
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Infective colitis|'''Infective colitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in fulminant colitis
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hyperactive 
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Stool culture]] and studies
* Shiga toxin in bloody diarrhea
* [[PCR]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |CT scan 
* Bowel wall thickening
* Edema
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Hepatitis|'''Viral hepatitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[RUQ]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in Hep A and E
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in fulminant hepatitis
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in acute
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |N
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Abnormal LFTs
* Viral serology
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* US
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Hep A and E have fecal-oral route of transmission 
* Hep B and C transmits via blood transfusion and sexual contact.
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Liver abscess|'''Liver abscess''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |RUQ
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal or hypoactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* CBC
* Blood cultures
* Abnormal [[Liver function test|liver function tests]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* US
* CT
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| colspan="1" rowspan="1" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Spontaneous bacterial peritonitis|'''Spontaneous bacterial peritonitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive in cirrhotic patients
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hypoactive
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Ascitic fluid [[PMN]]>250 cells/mm<small>³</small>
* Culture: Positive for single organism 
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Ultrasound for evaluation of liver cirrhosis
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Mesenteric ischemia|'''Mesenteric ischemia''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Periumbilical
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Positive if bowel becomes gangrenous
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive if bowel becomes gangrenous
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Positive if bowel becomes gangrenous
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hyperactive to absent
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Leukocytosis]] and [[lactic acidosis]]
* [[Amylase]] levels
* [[D-dimer]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |CT angiography
* SMA or SMV thrombosis
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Also known as abdominal angina  that worsens with eating
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Ischemic colitis|'''Acute ischemic colitis''']]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Hyperactive then absent
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Leukocytosis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Abdominal x-ray]]
* Distension and pneumatosis
CT scan
* Double halo appearance, thumbprinting 
* Thickening of bowel
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* May lead to shock
|-
|}
|}
<span style="font-size:85%">'''Abbreviations:'''
'''[[RUQ]]'''= Right upper quadrant of the abdomen, '''LUQ'''= Left upper quadrant, '''LLQ'''= Left lower quadrant, '''RLQ'''= Right lower quadrant, '''LFT'''= Liver function test, SIRS= [[Systemic inflammatory response syndrome]], '''[[ERCP]]'''= [[Endoscopic retrograde cholangiopancreatography]], '''IV'''= Intravenous, '''N'''= Normal, '''AMA'''= Anti mitochondrial antibodies, '''[[LDH]]'''= [[Lactate dehydrogenase]], '''GI'''= Gastrointestinal, '''CXR'''= Chest X ray, '''IgA'''= [[Immunoglobulin A]], '''IgG'''= [[Immunoglobulin G]], '''IgM'''= [[Immunoglobulin M]], '''CT'''= [[Computed tomography]], '''[[PMN]]'''= Polymorphonuclear cells, '''[[ESR]]'''= [[Erythrocyte sedimentation rate]], '''[[CRP]]'''= [[C-reactive protein]], TS= [[Transferrin saturation]], SF= Serum [[Ferritin]], SMA= [[Superior mesenteric artery]], SMV= [[Superior mesenteric vein]], ECG= [[Electrocardiogram]]</span>