Definition/General
Introduction:
Drug-induced colitis is iatrogenic inflammatory condition caused by medications
Shows variable histologic patterns depending on drug class
Reversible condition with drug discontinuation
Important differential for inflammatory bowel disease.
Origin:
Results from direct drug toxicity or immune-mediated mechanisms
Shows dose-dependent effects (some drugs)
Demonstrates hypersensitivity reactions
Associated with altered gut microbiome
Individual susceptibility varies.
Classification:
NSAID-induced colitis (most common)
Antibiotic-associated colitis (non-C
difficile)
Chemotherapy-induced colitis
Immunosuppressive drug colitis
Proton pump inhibitor colitis
SSRI-associated colitis.
Epidemiology:
Increasing incidence with polypharmacy
Elderly population at higher risk
Chronic medication users
Cancer patients (chemotherapy)
Underrecognized condition
Reversible nature often leads to resolution.
Clinical Features
Presentation:
Diarrhea (most common symptom)
Abdominal pain
Rectal bleeding (variable)
Nausea and vomiting
Drug exposure history
Temporal relationship with medication.
Symptoms:
Watery or bloody diarrhea
Crampy abdominal pain
Urgency
Mucus passage
Constitutional symptoms (fever, malaise)
Dehydration.
Risk Factors:
Advanced age (>65 years)
Polypharmacy
Chronic NSAID use
Chemotherapy treatment
Immunosuppression
Previous drug reactions.
Screening:
Detailed drug history
Temporal correlation
Colonoscopy (mucosal assessment)
Exclude other causes
Response to drug withdrawal.
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Gross Description
Appearance:
Variable endoscopic findings by drug class
Mucosal erythema and edema
Ulceration (NSAIDs)
Normal appearance (microscopic colitis)
Strictures (rare).
Characteristics:
Patchy mucosal changes
Right-sided predominance (some drugs)
Aphthous ulcers
Friable mucosa
Pseudomembranes (severe cases)
Normal intervening mucosa.
Size Location:
Variable distribution by drug
Right-sided colitis (NSAIDs)
Pan-colonic involvement (chemotherapy)
Rectal sparing (some drugs)
Small bowel involvement possible.
Multifocality:
Patchy involvement
Skip lesions
Dose-dependent severity
Temporal progression
Resolution with withdrawal.
Microscopic Description
Histological Features:
Variable patterns: acute colitis, microscopic colitis, eosinophilic colitis
Increased apoptosis (chemotherapy)
Eosinophilic infiltration (hypersensitivity)
Surface epithelial damage
Chronic inflammation.
Cellular Characteristics:
Eosinophils (allergic reactions)
Neutrophils (acute inflammation)
Apoptotic epithelial cells
Lymphocytes and plasma cells
Surface epithelial flattening.
Architectural Patterns:
Preserved crypt architecture (early)
Crypt distortion (chronic)
Surface ulceration
Increased intraepithelial lymphocytes (microscopic colitis pattern)
Subepithelial collagen thickening (some drugs).
Grading Criteria:
Mild: minimal inflammation, preserved architecture
Moderate: active inflammation, surface changes
Severe: ulceration, extensive inflammation
Drug-specific patterns.
Immunohistochemistry
Positive Markers:
CD3 (T lymphocytes)
CD20 (B lymphocytes)
CD68 (macrophages)
Mast cell tryptase (mast cells)
Cytokeratin (epithelium).
Negative Markers:
Specific infectious agents
Malignancy markers
IBD-specific markers
Autoimmune markers.
Diagnostic Utility:
Excludes other causes
Assesses inflammatory pattern
Identifies cell types
Usually not required
Clinical correlation more important.
Molecular Subtypes:
NSAID-induced (COX inhibition)
Chemotherapy-induced (cytotoxic)
Immune checkpoint inhibitor colitis
Antibiotic-associated
PPI-associated microscopic colitis.
Molecular/Genetic
Genetic Mutations:
Drug metabolism genes (CYP450 variants)
HLA associations (hypersensitivity)
Pharmacogenomic factors
Individual susceptibility genes
No specific driver mutations.
Molecular Markers:
Drug-specific pathways
COX inhibition (NSAIDs)
Immune activation (checkpoint inhibitors)
Apoptosis markers (chemotherapy)
Inflammatory mediators.
Prognostic Significance:
Reversibility with drug withdrawal
Dose-dependent severity
Individual sensitivity
Rechallenge risk
Alternative drug availability.
Therapeutic Targets:
Drug discontinuation (primary treatment)
Supportive care
Anti-inflammatory agents
Corticosteroids (severe cases)
Alternative medications.
Differential Diagnosis
Similar Entities:
Inflammatory bowel disease
Infectious colitis
Ischemic colitis
Microscopic colitis (idiopathic)
Radiation colitis
Pseudomembranous colitis.
Distinguishing Features:
Drug-induced colitis: Drug history, temporal relationship, reversibility
IBD: Chronic course, architectural changes
Infectious: Organisms identified
Ischemic: Watershed zones, vascular disease
Idiopathic microscopic colitis: No drug association.
Diagnostic Challenges:
Establishing temporal relationship
Excluding other causes
Recognizing drug-specific patterns
Multiple drug exposure
Rechallenge confirmation.
Rare Variants:
Immune checkpoint inhibitor colitis
Gold-induced colitis
Penicillamine colitis
SSRI-associated colitis
Combined drug toxicity.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type] from [anatomical location]
Drug History
Medications: [list drugs]. Duration: [timeline]. Temporal relationship: [onset after drug initiation]
Histologic Pattern
Pattern: [acute colitis/microscopic colitis/eosinophilic colitis]. Distribution: [patchy/diffuse]
Drug-Related Changes
Eosinophilia: [present/absent]. Apoptosis: [increased/normal]. Surface damage: [present/absent]
Inflammatory Features
Inflammation: [acute/chronic/mixed]. Severity: [mild/moderate/severe]
Other Causes
Infectious organisms: [not identified]. IBD features: [absent]
Recommendations
Consider drug withdrawal if clinically appropriate. Monitor for improvement after discontinuation.
Final Diagnosis
Drug-Induced Colitis - [specify suspected drug if known]