Chronic Colitis Differential Diagnosis: A Comprehensive Guide for Clinicians

Colitis, characterized by the inflammation of the colon’s mucosal lining, is a condition of increasing global prevalence. It manifests in both acute and chronic forms, presenting patients with a spectrum of symptoms including watery diarrhea, abdominal pain, tenesmus, urgency, fever, fatigue, and bloody stools. The diverse etiologies of colitis, ranging from infections and autoimmune disorders to ischemia and drug-induced reactions, pose a significant diagnostic challenge. This article provides an in-depth exploration of colitis, with a particular focus on the differential diagnosis of chronic colitis, aiming to equip clinicians with a robust framework for evaluation and management. Effective management of colitis necessitates a clear understanding of its underlying causes and clinical nuances. This review will delve into the etiology, epidemiology, pathophysiology, evaluation, management, and potential complications of colitis, emphasizing the crucial role of an interprofessional healthcare team in optimizing patient outcomes.

Objectives:

• Outline the epidemiological landscape of colitis.
• Elucidate the pathophysiological mechanisms underpinning colitis.
• Detail the management strategies available for colitis.
• Underscore the importance of collaborative care planning among healthcare practitioners in managing colitis to enhance patient outcomes and minimize morbidity.

Access free multiple choice questions on this topic.

Introduction

Chronic colitis, a persistent inflammation of the colon’s mucosal lining, is a growing health concern worldwide. While acute colitis often presents with distinct infectious etiologies, chronic colitis requires a more nuanced differential diagnosis to pinpoint the underlying cause and guide appropriate management. Patients commonly report symptoms such as persistent watery diarrhea, abdominal discomfort, tenesmus, urgency, fatigue, and hematochezia. The challenge in diagnosing chronic colitis lies in its varied origins, which include inflammatory bowel diseases (IBD), microscopic colitis, ischemic conditions, medication side effects, and colitis secondary to immunodeficiency or radiation exposure. Given the overlap in clinical presentations across different types of chronic colitis, a systematic approach is crucial for accurate assessment and differential diagnosis. This article aims to address this diagnostic complexity by providing a comprehensive review of the etiology, epidemiology, pathophysiology, clinical presentation, evaluation, differential diagnosis, complications, and management of chronic colitis, with a strong emphasis on the differential diagnostic process.

Etiology of Chronic Colitis

In adults, chronic colitis can stem from a multitude of factors. Accurate differential diagnosis relies on considering the following etiologies:

1. Inflammatory Bowel Disease (IBD): Ulcerative colitis (UC) and Crohn’s disease (CD) are primary considerations in chronic colitis. These autoimmune conditions involve chronic inflammation of the gastrointestinal tract. UC typically affects the colon and rectum, while CD can affect any part of the digestive tract, but frequently involves the colon.

2. Microscopic Colitis: This category encompasses collagenous colitis (CC) and lymphocytic colitis (LC). Microscopic colitis is characterized by chronic watery diarrhea with normal endoscopic findings, requiring biopsies for diagnosis. It’s more prevalent in older adults and associated with autoimmune disorders.

3. Ischemic Colitis: While often acute, ischemic colitis can become chronic or recurrent, particularly in individuals with underlying vascular disease or risk factors for hypoperfusion. Chronic ischemic colitis results from prolonged or repeated episodes of reduced blood flow to the colon.

4. Drug-Induced Colitis: Certain medications can induce chronic colitis-like symptoms. Non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and some immunosuppressants are among the potential culprits. A thorough medication history is crucial in the differential diagnosis.

5. Immune Deficiency Disorders: Conditions like HIV infection and other primary or secondary immunodeficiencies can predispose individuals to chronic colitis, often due to opportunistic infections or immune dysregulation.

6. Tuberculous Colitis: Although less common in Western countries, tuberculous colitis, caused by Mycobacterium tuberculosis, should be considered in the differential diagnosis, especially in endemic regions or in immunocompromised patients. Chronic tuberculous colitis can mimic Crohn’s disease.

7. Radiation Colitis: Patients who have undergone pelvic radiotherapy for cancers may develop chronic radiation colitis. This condition can manifest months to years after radiation therapy.

8. Infectious Colitis (Chronic or Persistent): While many infectious colitides are acute and self-limiting, some infections, such as cytomegalovirus (CMV) in immunocompromised individuals, or persistent Clostridioides difficile infection, can lead to chronic symptoms. Parasitic infections like Entamoeba histolytica, if untreated, can also cause chronic colitis.

Epidemiology of Chronic Colitis

Understanding the epidemiology of different types of colitis is crucial for differential diagnosis, as prevalence varies significantly based on etiology, age, and geographical location.

Inflammatory bowel disease (IBD), encompassing UC and CD, exhibits a rising global incidence and prevalence, particularly in North America and Europe. The prevalence in the USA is approximately 263 per 100,000 adults, highlighting IBD as a significant cause of chronic colitis.

Microscopic colitis is most commonly diagnosed in older adults, typically between 50 and 70 years of age. It is more prevalent in women, with a female-to-male ratio higher in collagenous colitis. The incidence ranges from 1 to 30 per 100,000 person-years, indicating its relatively common occurrence as a cause of chronic watery diarrhea in the elderly.

Ischemic colitis incidence increases with age and comorbidities. While acute ischemic colitis is more frequently reported, chronic or recurrent forms are also recognized, especially with an aging population and increased prevalence of cardiovascular risk factors.

Tuberculous colitis remains endemic in many parts of the world, and its resurgence in some Western countries necessitates its consideration in the differential diagnosis, especially in specific populations at risk for tuberculosis.

Drug-induced colitis prevalence is difficult to ascertain precisely, as it depends on medication usage patterns. However, with widespread use of NSAIDs and PPIs, drug-induced colitis represents a relevant differential diagnosis, particularly in chronic cases with no other clear etiology.

Pathophysiology of Chronic Colitis

The pathophysiology of chronic colitis varies depending on the underlying etiology, but common themes involve persistent mucosal inflammation and disruption of the intestinal barrier.

In ulcerative colitis, chronic inflammation is typically confined to the mucosa and submucosa of the colon and rectum. The inflammatory process is characterized by a continuous pattern, often starting in the rectum and extending proximally. Chronic inflammation leads to mucosal ulceration, crypt distortion, and goblet cell depletion.

Crohn’s disease pathophysiology involves transmural inflammation, meaning it affects all layers of the bowel wall. This can result in strictures, fistulas, and abscesses. The inflammation is often discontinuous or “skip lesions,” and granulomas are a hallmark histological feature. Chronic inflammation in CD is driven by a complex interplay of genetic predisposition, immune dysregulation, and environmental factors.

Microscopic colitis, in both collagenous and lymphocytic subtypes, is characterized by inflammation at a microscopic level. Collagenous colitis features a thickened subepithelial collagen band, while lymphocytic colitis shows increased intraepithelial lymphocytes. The exact pathophysiology is not fully understood but is thought to involve immune-mediated mechanisms and altered intestinal permeability.

Ischemic colitis pathophysiology in chronic cases involves repeated or persistent hypoperfusion, leading to chronic mucosal damage and inflammation. Reperfusion injury can exacerbate the damage. Underlying vascular disease, such as atherosclerosis, and systemic conditions that compromise blood flow are key factors.

Drug-induced colitis mechanisms are diverse and drug-specific. NSAIDs, for example, can reduce prostaglandin synthesis, impairing mucosal protection and leading to inflammation. Immunosuppressants can alter the gut microbiome or directly injure the colonic mucosa in some cases.

Immune deficiency-related colitis pathophysiology depends on the specific immunodeficiency. In HIV, for instance, opportunistic infections like CMV can cause chronic colitis. Immune dysregulation can also contribute to chronic inflammation in the absence of overt infection.

Tuberculous colitis pathophysiology involves infection with Mycobacterium tuberculosis, leading to granulomatous inflammation and caseation necrosis in the colon. Chronic infection and immune response contribute to tissue damage.

Radiation colitis results from radiation-induced damage to the colonic mucosa and vasculature. Chronic radiation colitis involves fibrosis, vascular changes, and persistent inflammation, leading to symptoms that can last for years after radiation therapy.

Histopathology in Differential Diagnosis

Histopathology plays a vital role in the differential diagnosis of chronic colitis, particularly when endoscopy findings are non-specific or to differentiate between various inflammatory conditions.

In ulcerative colitis, biopsies show chronic mucosal inflammation with crypt distortion, basal plasmacytosis, and reduced goblet cells. Neutrophils may be present in the lamina propria and epithelium during active phases, but granulomas are absent, aiding in differentiation from Crohn’s disease.

Crohn’s disease histopathology often reveals transmural inflammation with lymphoid aggregates, submucosal fibrosis, and granulomas (non-caseating). “Skip lesions” are also reflected histologically, with areas of normal mucosa interspersed with inflammation.

Microscopic colitis is diagnosed based on microscopic findings in colonic biopsies from patients with chronic watery diarrhea and macroscopically normal mucosa. Collagenous colitis is characterized by a thickened subepithelial collagen band (>10 μm) and increased intraepithelial lymphocytes. Lymphocytic colitis shows increased intraepithelial lymphocytes (>20 per 100 epithelial cells) without a thickened collagen band.

Ischemic colitis histopathology varies with severity and chronicity. Chronic ischemic colitis may show mucosal atrophy, fibrosis, and hemosiderin-laden macrophages. Acute phases might show ulceration and necrosis, but these are less prominent in chronic cases.

Drug-induced colitis histopathology is variable and depends on the drug. Some patterns can mimic microscopic colitis (lymphocytic or collagenous features), while others may resemble ischemic colitis or acute infectious colitis. Histology is supportive but not always diagnostic of drug etiology.

Tuberculous colitis histopathology typically shows granulomatous inflammation with caseation necrosis. Acid-fast bacilli staining may be positive for Mycobacterium tuberculosis, but is not always present.

Radiation colitis biopsies may show fibrosis, vascular ectasia, and atypical stromal cells. Chronic radiation changes can be subtle and require correlation with clinical history.

History and Physical Examination in Chronic Colitis

A detailed history and physical examination are crucial for narrowing the differential diagnosis of chronic colitis. Key aspects to consider include:

History:

• Symptom onset and duration: Chronic colitis implies symptoms persisting for weeks to months. Differentiate from acute onset infectious colitis.
• Stool characteristics: Frequency, consistency (watery vs. loose), presence of blood, mucus. Chronic watery diarrhea is typical in microscopic colitis. Bloody diarrhea is more common in IBD and ischemic colitis.
• Abdominal pain: Location, character, and relation to bowel movements. Pain in UC and CD can vary. Ischemic colitis often presents with pain after eating.
• Extra-intestinal symptoms: Arthralgias, eye symptoms (uveitis, episcleritis), skin lesions (erythema nodosum, pyoderma gangrenosum) suggest IBD.
• Weight loss, fatigue, fever: Systemic symptoms may be present in IBD, tuberculous colitis, and some infectious colitides.
• Medication history: Detailed list of current and recent medications to evaluate for drug-induced colitis.
• Past medical history: Known autoimmune disorders, cardiovascular disease, immunodeficiency, cancer history (radiation colitis risk), travel history (infectious etiologies).
• Smoking history: Smoking is associated with increased risk of Crohn’s disease and decreased risk of ulcerative colitis and microscopic colitis.
• Family history: Family history of IBD increases the likelihood of UC or CD.

Physical Examination:

• General appearance: Assess for signs of systemic illness, dehydration, weight loss.
• Abdominal examination: Tenderness, distension, bowel sounds. Peritoneal signs are usually absent in chronic colitis unless complications like toxic megacolon or perforation occur.
• Rectal examination: Assess for perianal disease (fistulas, fissures suggestive of Crohn’s), rectal bleeding, and masses.
• Extra-intestinal manifestations: Examine for joint swelling, skin lesions, eye inflammation.

Evaluation and Differential Diagnosis

The evaluation of chronic colitis is aimed at establishing a definitive diagnosis and differentiating between various etiologies. The diagnostic approach typically involves a stepwise process:

1. Initial Laboratory Tests:

   • Complete Blood Count (CBC): Assess for anemia (chronic blood loss in IBD, ischemic colitis), leukocytosis (inflammation, infection), thrombocytosis.
   • Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP): Markers of inflammation, elevated in IBD and some infections, but may be normal in microscopic colitis.
   • Electrolytes, renal function: Assess for dehydration and electrolyte imbalances due to chronic diarrhea.
   • Stool studies:
     • Stool culture: Rule out bacterial pathogens, especially if infectious colitis is suspected. May be less helpful in chronic cases unless specific persistent infections are considered.
     • Stool for ova and parasites: Exclude parasitic infections like Entamoeba histolytica.
     • • *Clostridioides difficile toxin assay:** Consider in patients with antibiotic exposure or healthcare-associated diarrhea. May be relevant in chronic or recurrent diarrhea.
     • Fecal calprotectin: Marker of intestinal inflammation, elevated in IBD and infectious colitis, less consistently elevated in microscopic colitis. Helpful in differentiating inflammatory from functional bowel disorders.

2. Endoscopy with Biopsy:

   • Colonoscopy or flexible sigmoidoscopy: Essential for visual inspection of the colonic mucosa and obtaining biopsies.
     • Ulcerative colitis: Continuous mucosal inflammation, ulcers, loss of vascular pattern.
     • Crohn’s disease: Patchy inflammation, aphthous ulcers, cobblestone appearance, strictures.
     • Ischemic colitis: Pale mucosa, petechiae, cyanotic mucosa, strictures in chronic cases.
     • Microscopic colitis: Macroscopically normal mucosa. Biopsies are crucial for diagnosis.
     • Drug-induced colitis: Variable endoscopic appearance, may be normal, erythematous, or ulcerative.
     • Radiation colitis: Telangiectasias, mucosal friability, strictures.
     • Tuberculous colitis: Ileocecal involvement common, ulcers, masses, strictures.

3. Histopathological Examination of Biopsies: As detailed in the Histopathology section, biopsies are critical for definitive diagnosis, especially in differentiating microscopic colitis and characterizing inflammatory patterns in other forms of colitis.

4. Serological Tests:

   • IBD serologies:
     • Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA): Helpful in differentiating UC and CD, although not always diagnostic. pANCA is more common in UC, ASCA in CD.
   • Celiac serology: Tissue transglutaminase IgA antibodies to rule out celiac disease, especially if diarrhea is a prominent symptom.

5. Imaging Studies:

   • Abdominal CT scan or MRI: Useful to assess for complications like strictures, fistulas, abscesses (in Crohn’s disease), and to evaluate for ischemic colitis (CT angiography). May also help rule out other abdominal pathologies like diverticulitis or malignancy.
   • Small bowel follow-through or MR enterography: Evaluate for small bowel Crohn’s disease.

6. Specific Tests Based on Clinical Suspicion:

   • Tuberculin skin test or Interferon-gamma release assay (IGRA): If tuberculous colitis is suspected, especially in high-risk populations.
   • CMV PCR or immunohistochemistry of biopsies: In immunocompromised patients if CMV colitis is considered.
   • D-lactate levels: May be elevated in ischemic colitis, but not routinely used.

Differential Diagnosis of Chronic Colitis:

The differential diagnosis for chronic colitis is broad and requires careful consideration of clinical, endoscopic, and histological findings. Key conditions to differentiate include:

• Irritable Bowel Syndrome (IBS): IBS is a functional bowel disorder characterized by abdominal pain and altered bowel habits, but without macroscopic or microscopic inflammation. Fecal calprotectin is usually normal in IBS. Endoscopy and biopsies are normal. Differentiating IBS from mild microscopic colitis can be challenging and requires biopsies in patients with persistent watery diarrhea despite IBS treatments.

• Celiac Disease: Can present with chronic diarrhea and malabsorption. Celiac serology and upper endoscopy with duodenal biopsies are diagnostic. Microscopic colitis can coexist with celiac disease, so biopsies should still be considered in patients with persistent diarrhea even after gluten-free diet in celiac disease.

• Colorectal Cancer: Although typically presents with rectal bleeding and change in bowel habits, it can mimic colitis in some cases, especially inflammatory carcinoma. Colonoscopy is essential to rule out malignancy in all patients with colitis symptoms, particularly in older individuals or those with alarm symptoms.

• Diverticulitis (Chronic or Segmental Colitis Associated with Diverticulosis – SCAD): Diverticulosis is common, and SCAD can present with chronic colitis-like symptoms. Colonoscopy can identify diverticula and associated inflammation. Biopsies can differentiate SCAD from IBD.

• Toxic Megacolon: A severe complication of colitis (usually UC or C. difficile colitis), presenting with colonic dilatation and systemic toxicity. Requires urgent management. Diagnosis is clinical and radiographic (abdominal X-ray).

• Chronic Viral/Bacterial Gastroenteritis: Persistent infections, such as CMV in immunocompromised individuals or chronic parasitic infections, need to be considered. Stool studies and specific viral testing are indicated.

• Other Types of Colitis: Distinguishing between UC and CD is crucial, as management differs. Microscopic colitis, ischemic colitis, drug-induced colitis, radiation colitis, and tuberculous colitis all have specific diagnostic criteria and management approaches.

Treatment and Management of Chronic Colitis

Management of chronic colitis is etiology-specific and aims to induce and maintain remission, alleviate symptoms, and prevent complications.

• Inflammatory Bowel Disease (IBD):

  • Ulcerative Colitis: 5-aminosalicylates (5-ASA) are first-line for mild to moderate UC. Corticosteroids for induction of remission in moderate to severe flares. Immunomodulators (azathioprine, 6-mercaptopurine) and biologic therapies (anti-TNF agents, anti-integrins, anti-IL-12/23) are used for maintenance and in refractory cases. Surgery (colectomy) is considered for severe, refractory UC or complications.
  • Crohn’s Disease: Management is more complex. Corticosteroids for induction, but not for maintenance. Immunomodulators (azathioprine, methotrexate) and biologics (anti-TNF, anti-integrins, anti-IL-12/23, anti-IL-23) are mainstay for maintenance and moderate to severe disease. Antibiotics may be used for perianal disease or infectious complications. Nutritional support is important. Surgery is often needed for complications like strictures, fistulas, abscesses, but is not curative.

• Microscopic Colitis: Budesonide is highly effective for inducing remission. Bismuth subsalicylate and anti-diarrheal agents can provide symptomatic relief. Immunomodulators or biologics may be needed in refractory cases. Smoking cessation is important.

• Ischemic Colitis: Management depends on severity. Mild cases may resolve with supportive care (bowel rest, IV fluids). Moderate to severe cases may require antibiotics, optimization of hemodynamics. Surgical resection is needed for bowel infarction, perforation, or failure of medical management. Management of underlying cardiovascular risk factors is crucial to prevent recurrence.

• Drug-Induced Colitis: Discontinuation of the offending medication is the primary step. Symptomatic treatment with anti-diarrheal agents may be used. In severe cases, corticosteroids may be considered.

• Immune Deficiency-Related Colitis: Treatment focuses on managing the underlying immunodeficiency and treating opportunistic infections (e.g., antiviral therapy for CMV colitis). Immunomodulation may be considered in some cases.

• Tuberculous Colitis: Multi-drug anti-tuberculosis therapy (isoniazid, rifampin, pyrazinamide, ethambutol) for 9 months is the standard treatment. Corticosteroids may be used as adjunct therapy in severe cases.

• Radiation Colitis: Management is primarily symptomatic. Anti-diarrheals, 5-ASA enemas or suppositories, sucralfate enemas may provide relief. Severe cases may require endoscopic or surgical intervention for strictures or bleeding.

Complications of Chronic Colitis

Complications of chronic colitis are diverse and depend on the underlying etiology and severity of inflammation. Potential complications include:

• Intestinal perforation: Risk is higher in severe IBD and toxic megacolon.
• Bowel strictures, fistulas, abscesses, and intestinal obstruction: Common in Crohn’s disease due to transmural inflammation.
• Toxic megacolon: Life-threatening complication of severe colitis, particularly UC and C. difficile colitis.
• Anemia and malnutrition: Due to chronic inflammation, malabsorption, and blood loss, especially in IBD.
• Fecal incontinence: Resulting from chronic rectal inflammation and damage to anal sphincter function.
• Increased risk of colorectal cancer: Long-standing ulcerative colitis and Crohn’s colitis increase colorectal cancer risk, necessitating regular surveillance colonoscopy.
• Extra-intestinal manifestations: Arthritis, eye inflammation, skin lesions, liver disease, and thromboembolic events can occur in IBD.
• Psychological impact: Chronic colitis can significantly impact quality of life, leading to anxiety, depression, and social isolation.

Pearls and Key Considerations in Chronic Colitis Differential Diagnosis

• Persistent watery diarrhea in older adults: Always consider microscopic colitis. Obtain biopsies even if colonoscopy is normal.
• Chronic colitis symptoms with a history of medication use: Thorough medication review is essential to rule out drug-induced colitis.
• Bloody diarrhea and abdominal pain: Favor IBD or ischemic colitis. Differentiate based on clinical context, endoscopy, and histology.
• Extraintestinal symptoms: Strongly suggest IBD.
• Immunocompromised patients: High risk for infectious colitis, including CMV and C. difficile. Consider tuberculous colitis in appropriate epidemiological settings.
• Correlation of clinical, endoscopic, and histological findings: Essential for accurate differential diagnosis and management.
• Consider functional bowel disorders (IBS) but exclude organic causes: Rule out inflammatory and structural diseases before diagnosing IBS, especially in patients with new-onset or worsening symptoms.
• Regular surveillance for colorectal cancer in long-standing IBD colitis.

Enhancing Healthcare Team Outcomes

Managing chronic colitis effectively requires a collaborative, interprofessional team approach. General practitioners play a crucial role in initial recognition, referral, and ongoing support. Gastroenterologists are central to diagnosis, endoscopic evaluation, and medical management. Pathologists are essential for histological diagnosis and differential diagnosis. Radiologists contribute through imaging to assess disease extent and complications. Pharmacists ensure appropriate medication management and patient education. Nurses provide essential patient education, monitoring, and support. Dietitians offer nutritional counseling, particularly important in IBD and malabsorption. Mental health professionals address the psychological impact of chronic disease. Surgeons are involved in managing complications and surgical options for refractory IBD or ischemic colitis. Effective communication and coordination among all team members are paramount to optimize patient care and outcomes in chronic colitis. [Level V]

Review Questions

[Include review questions from the original article here if applicable, or create new ones focusing on differential diagnosis of chronic colitis.]

Figure

Infant With Necrotizing Enterocolitis, Radiograph. Children (in daycare centers), older adults (in nursing homes), and immunocompromised individuals are susceptible to these infections. RadsWiki

Figure

Gross Pathology, Neonatal, Necrotizing enterocolitis, Alimentary tract of infant, intestinal necrosis, pneumatosis intestinalis, perforation site shown by arrow Contributed by The Centers for Disease Control and Prevention (CDC)

Figure

Micrograph of Clostridioides difficile Showing Colitis. Pathological micrograph displays gram-positive C difficile bacteria, indicating colitis infection. Contributed by LS Wiggs and J Carr; Centers for Disease Control and Prevention

Figure

Pseudomembranous colitis image donated by sbhimji

Figure

Amebic Colitis Pathology Outlines

References

1.Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. [PubMed: 22001864]

2.Yadav S, Dave M, Edakkanambeth Varayil J, Harmsen WS, Tremaine WJ, Zinsmeister AR, Sweetser SR, Melton LJ, Sandborn WJ, Loftus EV. A population-based study of incidence, risk factors, clinical spectrum, and outcomes of ischemic colitis. Clin Gastroenterol Hepatol. 2015 Apr;13(4):731-8.e1-6; quiz e41. [PMC free article: PMC4326614] [PubMed: 25130936]

3.Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999 Aug 18;282(7):677-86. [PubMed: 10517722]

4.Napolitano LM, Edmiston CE. Clostridium difficile disease: Diagnosis, pathogenesis, and treatment update. Surgery. 2017 Aug;162(2):325-348. [PubMed: 28267992]

5.Jessurun J. The Differential Diagnosis of Acute Colitis: Clues to a Specific Diagnosis. Surg Pathol Clin. 2017 Dec;10(4):863-885. [PubMed: 29103537]

6.Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017 Apr 29;389(10080):1756-1770. [PMC free article: PMC6487890] [PubMed: 27914657]

7.Pardi DS. Diagnosis and Management of Microscopic Colitis. Am J Gastroenterol. 2017 Jan;112(1):78-85. [PubMed: 27897155]

8.Brown WR, Tayal S. Microscopic colitis. A review. J Dig Dis. 2013 Jun;14(6):277-81. [PubMed: 23419063]

9.Ianiro G, Cammarota G, Valerio L, Annicchiarico BE, Milani A, Siciliano M, Gasbarrini A. Microscopic colitis. World J Gastroenterol. 2012 Nov 21;18(43):6206-15. [PMC free article: PMC3501768] [PubMed: 23180940]

10.Washington C, Carmichael JC. Management of ischemic colitis. Clin Colon Rectal Surg. 2012 Dec;25(4):228-35. [PMC free article: PMC3577613] [PubMed: 24294125]

11.Tortora A, Purchiaroni F, Scarpellini E, Ojetti V, Gabrielli M, Vitale G, Giovanni G, Gasbarrini A. Colitides. Eur Rev Med Pharmacol Sci. 2012 Nov;16(13):1795-805. [PubMed: 23208963]

12.Nguyen GC, Loftus EV, Hirano I, Falck-Ytter Y, Singh S, Sultan S., AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Management of Crohn’s Disease After Surgical Resection. Gastroenterology. 2017 Jan;152(1):271-275. [PubMed: 27840074]

13.Marchioni Beery R, Kane S. Current approaches to the management of new-onset ulcerative colitis. Clin Exp Gastroenterol. 2014;7:111-32. [PMC free article: PMC4026549] [PubMed: 24872716]

14.Nguyen GC, Smalley WE, Vege SS, Carrasco-Labra A., Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Medical Management of Microscopic Colitis. Gastroenterology. 2016 Jan;150(1):242-6; quiz e17-8. [PubMed: 26584605]

15.Trotter JM, Hunt L, Peter MB. Ischaemic colitis. BMJ. 2016 Dec 22;355:i6600. [PubMed: 28007701]

16.Mukewar S, Mukewar S, Ravi R, Prasad A, S Dua K. Colon tuberculosis: endoscopic features and prospective endoscopic follow-up after anti-tuberculosis treatment. Clin Transl Gastroenterol. 2012 Oct 11;3(10):e24. [PMC free article: PMC3491534] [PubMed: 23238066]

17.Gan SI, Beck PL. A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol. 2003 Nov;98(11):2363-71. [PubMed: 14638335]

18.Ausch C, Madoff RD, Gnant M, Rosen HR, Garcia-Aguilar J, Hölbling N, Herbst F, Buxhofer V, Holzer B, Rothenberger DA, Schiessel R. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201. [PubMed: 16466559]

Disclosure: Samy Azer declares no relevant financial relationships with ineligible companies.

Disclosure: Yan Sun declares no relevant financial relationships with ineligible companies.