Drug-induced colitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qasim Salau, M.B.B.S., FMCPaed [2]

Synonyms and keywords: Drug-related colitis, Drug-induced enterocolitis, Non-steroidal anti-inflammatory drug (NSAID) induced colitis; Chemotherapeutic drug-induced colitis

Historical Perspective

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

• There is no established classification method for drug-induced colitis. However, it may be classified based on the pathophysiology pattern, type of drug and duration of symptoms.

Classification based on pathophysiology pattern

Based on the pathophysiology, drug-induced colitis may be classified into:

Pathophysiologic pattern of colitis	Drugs
Focal active colitis	NSAIDs, sodium phosphate (oral)
Eosinophilic colitis	NSAIDs, carbamazepine, antiplatelet drugs, estrogen, progesteron, gold
Ischemic colitis	NSAIDs, digoxin, diuretics, cocaine, ergotamine, serotonin agonists/antagonists, amphetamines, glutaraldehyde, antibiotics, chemotherapy drugs, drugs that cause constipation, laxatives, vasopressor agents, estrogen, progesteron, mycophenolic acid
Microscopic colitis	NSAIDs, Protein pump inhibitors (lansoprazole), H2 receptor blockers (e.g. ranitidine), ticlopidine, simvastatin, carbamazepine, sertraline, oral penicillin
Pseudomembranous colitis	Antibiotic-associated Clostridium difficile colitis (e.g. penicillins, clindamycin, cephalosporins, fluoroquinolones)
Apoptotic colitis	NSAIDs, oral sodium phosphate, laxatives, chemotherapy drugs (especially anti-metabolites), and cyclosporine A
Neutropenic enterocolitis	Chemotherapy drugs
Immune-mediated colitis	Antibody to cytotoxic T-lymphocyte–associated antigen (CTLA4)

Classification based on type of drugs

Drug-induced colitis can be classified based on the type of drugs into:

• Non-steroidal anti-inflammatory drugs (NSAID)-induced colitis
• Chemotherapy drug-induced colitis
• Antibiotic-associated Clostridium difficile colitis
• H2 receptor blockers induced colitis

Classification based on duration of symptoms

Based on the duration of symptoms, drug-induced colitis can be classified into:

• Acute
• Chronic e.g. diaphragm disease (results from prolonged use of NSAIDs)

Pathophysiology

Pathogenesis

• The pathogenesis of drug-induced colitis depends on the causative drug. The most common drugs implicated in drug-induced colitis are NSAIDs.
  • The exact mechanism by which NSAID cause colitis is not completely understood. NSAIDs can either induce new-onset colitis or exacerbate a pre-existing colitis.
    • NSAIDs inhibit cyclooxygenase and thus prostaglandin production. Prostaglandin helps to maintain mucosal integrity. NSAIDs also impair oxidative phosphorylation, increasing risk of oxidative injury to the gut.
    • Direct damage to the intestinal mucosa is another proposed mechanism in NSAID related injury, since the rectum is often spared with colitis mainly limited to the right side of the colon.
    • Increased intestinal permeability to antigens following the use of NSAIDs is another hypothesized mechanism. This is said to cause the activation of the immune system and subsequent inflammation.

Genetics

• There is no specific genetic cause for drug-induced colitis

Gross Pathology

Gross pathology findings in drug-induced colitis depends on the causative drug.

• NSAID-induced colitis is characterized by nonspecific mucosal ulcers of varying degree, with intervening areas of normal mucosa. Perforations and fibrosis may also be seen. The lesions are predominantly on the right, sparing the rectum.

• Pseudomembranes may be seen in NSAID colitis and antibiotic induced Clostridium difficile colitis.

Microscopic Histopathology

• On histology, NSAID-induced colitis findings include ulcers that are often discrete and superficial with increased polymorphonuclear inflammatory cells especially eosinophils. The area of pathology is surrounded by normal colonic mucosa. Submucosal fibrosis with disruption of normal mucosal architecture is seen in diaphragm disease.

• Other histology findings associated with drug-induced colitis include increased epithelial apoptosis, especially involvement of the crypts, presence of pseudomembranes and features of microscopic colitis (presence of lymphocytes within the crypts in an otherwise normal looking mucosa).

Causes

• [Disease name] may be caused by either [cause1], [cause2], or [cause3].
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

Differentiating [disease name] from other Diseases

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

The table below lists the differential diagnosis of common causes of colitis:

Diseases	History and Symptoms				Physical Examination				Laboratory findings				Other Findings
	Diarrhea	Rectal bleeding	Abdominal pain	Atopy	Dehydration	Fever	Hypotension	Malnutrition	Blood in stool (frank or occult)	Microorganism in stool	Pseudomembranes on endoscopy	Lab Test 4
Allergic Colitis	+	++	+	++					++
Chemical colitis	+	++	++		+	+		+			+
Infectious colitis	++	++	+		+++	+++	++		+	++	+
Radiation colitis	+	++	+		+			+
Ischemic colitis	+	++	++			+		++		+

Epidemiology and Demographics

• The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

• There are no [imaging study] findings associated with [disease name].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].