Inflammatory Bowel Disease [Speed]

Expanded Outline and Basic Pre-study of Inflammatory Bowel Disease (IBD) Content:

1. Introduction to IBD

• Definition and overview
• Types of IBD: Crohn's Disease (CD) and Ulcerative Colitis (UC)

2. Genetics of IBD

• Genetic influences and risk factors
• Key genetic loci: NOD2 gene for CD, HLA for UC
• Ethnic variation in genetic architecture
• Positive family history as a major risk factor
• Genetic syndromes related to IBD
• Twin concordance studies

3. Clinical Features of IBD

• Differentiating features of CD and UC
• Early lesions and ulcer characteristics
• Inflammation patterns and complications
• Distribution patterns in CD and UC

4. Classification Systems

• Montreal Classification for IBD
• Severity assessment and classification based on clinical presentation

5. Extraintestinal Manifestations

• Common extraintestinal symptoms
• Arthritis, PSC, and their implications
• Cutaneous and ocular manifestations

6. Management of IBD

• Induction and maintenance of remission in UC and CD
• Use of mesalamine, corticosteroids, infliximab, and other medications
• Combination therapy strategies
• Risk stratification and tailored medical therapy

7. Screening and Monitoring

• Screening protocols for colorectal neoplasia
• True Love and Witts criteria for assessing UC severity
• Regular monitoring and follow-up recommendations

8. Surgical Management

• Indications for surgery in UC and CD
• Procedures for acute severe cases like toxic megacolon
• Elective surgical options and their appropriateness
• Special considerations for pouchitis and chronic antibiotic-refractory cases

9. Pouchitis and Pouchitis Disease Activity Index (PDAI)

• Risk factors for pouchitis
• PDAI scoring system: criteria and total score
• Management strategies including antibiotics, probiotics, and steroids
• Chronic Antibiotic-Refractory Pouchitis (CARP): causes and treatment

10. Diverticular Disease

• Overview and types (true vs. false diverticula)
• Risk factors and common sites
• Clinical features and complications like colovesical fistula
• Modified Hinchey Classification for diverticulitis severity
• Management strategies based on severity
• Surgical options for complications like abscess and perforation

11. Case Scenarios and Practical Applications

• Detailed case studies illustrating clinical decision-making
• Management strategies for acute flares, refractory cases, and complications like toxic megacolon and pouchitis

12. Recent Advances and Future Directions

• Emerging therapies and ongoing research in IBD management
• Genetic and immunological insights contributing to personalized medicine

---

Basic Pre-study of Content

1. Genetic Influences and Risk Factors:

• IBD is polygenic, with multiple genetic loci contributing to disease susceptibility.
• CD has a stronger genetic component compared to UC.
• Key genetic markers include the NOD2 gene for CD among Caucasians and HLA for UC across populations.

• Genetic susceptibility varies across ethnic groups, challenging the notion of a uniform genetic architecture for IBD​​.

  (Inflammatory Bowel Dise…)

2. Clinical Features and Classification:

• CD and UC have distinct clinical features, with CD often presenting with transmural inflammation and skip lesions, while UC typically involves continuous mucosal inflammation starting from the rectum.

• The Montreal Classification helps in categorizing IBD based on age at diagnosis, disease location, and disease behavior​​.

  (Inflammatory Bowel Dise…)

3. Extraintestinal Manifestations:

• Extraintestinal manifestations are more common in CD, with arthritis being the most frequent in UC.

• PSC is an important consideration, especially in UC, due to its independent disease course and increased risk of colonic neoplasia​​.

  (Inflammatory Bowel Dise…)

4. Management Strategies:

• Induction and maintenance of remission involve a combination of therapies tailored to disease severity and patient response.
• Biological therapies like infliximab are crucial for both induction and maintenance, especially in steroid-dependent or refractory cases.

• Surgical intervention is indicated for severe cases, including toxic megacolon and chronic refractory disease​​.

  (Inflammatory Bowel Dise…)

5. Screening and Monitoring:

• Regular screening for colorectal neoplasia is recommended, starting 10 years from the onset of colitis.

• The True Love and Witts criteria focus on clinical parameters to assess UC severity, emphasizing stool frequency, ESR, and hemoglobin levels​​.

  (Inflammatory Bowel Dise…)

6. Pouchitis and PDAI:

• Pouchitis is more common in patients with UC than FAP, with risk factors including PSC and NSAID use.
• The PDAI is used to score pouchitis severity, with a score greater than 7 indicating active pouchitis.

• Management includes antibiotics, probiotics, and steroids, with special consideration for chronic antibiotic-refractory pouchitis (CARP)​​.

  (Inflammatory Bowel Dise…)

7. Diverticular Disease:

• Diverticular disease includes true and false diverticula, with false diverticula being more common.
• Risk factors include a Western diet, obesity, and smoking, with common sites being the sigmoid and descending colon.

• The Modified Hinchey Classification is used to assess the severity of diverticulitis, guiding management strategies from antibiotics to surgical intervention​​.

  (Inflammatory Bowel Dise…)

8. Case Management:

• Practical case scenarios provide insight into real-world management of acute flares, refractory cases, and complications like toxic megacolon and pouchitis.
• The decision-making process involves assessing disease severity, response to initial therapy, and considering rescue therapies or surgical option

---

Genetics of IBD:

Genetic Influences and Risk Factors in Inflammatory Bowel Disease (IBD)

Answer: D

Explanation:

1. Genetic Influence in IBD:
   • Polygenic Nature: Both UC and CD are polygenic diseases, meaning they are influenced by multiple genes.
   • Stronger Genetic Influence in CD: There is a stronger genetic influence in CD compared to UC.
2. Key Genetic Risk Factors:
   • NOD2 for CD: In Caucasians, the NOD2 gene is a significant risk factor for CD.
   • HLA for UC: For all populations, HLA (Human Leukocyte Antigen) is a major risk factor for UC.
3. Ethnic Variation in Genetic Architecture:
   • IBD Genetic Loci: There are more than 200 confirmed IBD loci.
     • 37 unique to CD.
     • 27 unique to UC.
     • 137 common to both CD and UC.
   • Ethnic Differences: The genetic architecture of IBD varies across diverse ethnic populations, indicating that genetic susceptibility can differ based on ethnic background.
4. Incorrect Statement:
   • Option D: The statement that the genetic architecture of IBD is consistent across all ethnic populations is incorrect. There are significant variations in genetic susceptibility among different ethnic groups.

Additional Key Points on Genetics:

• Positive Family History: The greatest risk factor for IBD is a positive family history, with first-degree relatives of IBD patients having an approximately 15-fold higher risk for IBD than the general population.
• Shared Susceptibility Genes: IBD shares susceptibility genes with other immune-mediated disorders.
• Homeostatic Pathways: Identified IBD gene loci can be grouped into several important homeostatic pathways, including:
  • Innate Immunity:
    • Autophagy (in CD)
    • Other types of antimicrobial defense
    • IL-17/IL-23 pathway
  • Adaptive Immunity
  • Barrier Function and Epithelial Restitution
• Polygenic Diseases: Both UC and CD are polygenic, involving multiple genes.
• Ethnic Differences: The genetic architecture of IBD varies across diverse ethnic populations.
• Genetic Syndromes: Some genetic syndromes (e.g., glycogen storage disease type 1b, Hermansky-Pudlak syndrome) have phenotypes resembling IBD.
• Twin Concordance Studies:
  • CD: Concordance among monozygotic twins ranged from 35% to 58%, while dizygotic twin concordance ranged from 0% to 4%.
  • UC: Monozygotic concordance ranged from 16% to 19%, and dizygotic concordance ranged from 0% to 5%.
  • These studies confirmed the contribution of both genes and the environment in IBD and highlighted the stronger genetic influence in CD compared with UC.

Conclusion:

The genetic architecture of IBD is not consistent across all ethnic populations; it varies, reflecting diverse genetic backgrounds. Therefore, the correct answer is D.

MCQ - Features of Ulcerative Colitis

Answer: A

Explanation:

According to the provided image comparing Crohn's colitis and ulcerative colitis:

• Ulcerative Colitis:
  • Common features include superficial ulceration, rectal bleeding, continuous colonic involvement starting from the rectum, and toxic megacolon.
  • Nodularity on barium studies is a feature of Ulcerative colitis.
  • Aphthous ulcers & Non Caseating Granuloma’s, , cobblestone, or linear ulceration patterns are typically seen in Crohn's disease and not in ulcerative colitis.

Comparison of Crohn's Disease and Ulcerative Colitis

Feature	Crohn's Disease	Ulcerative Colitis
Granuloma	Non-caseating granuloma; involves both affected and unaffected bowel, any layer, mesenteric lymph node	No granuloma, loss of vascular pattern is the earliest lesion
Earliest Lesion	Aphthous ulcer	Loss of vascular pattern
Ulcer Characteristics	Linear, serpiginous, cobblestone; deep ulcers, bear claw	Granular mucosa, punctate ulcer, pseudopolyps
Long-standing Disease Features	-	Atrophic and featureless mucosa, cryptitis, crypt abscess, goblet cell mucin depletion
Inflammation	Transmural inflammation, lymphoid aggregates in submucosa	Inflammation limited to mucosa and submucosa; deeper inflammation in severe cases
Complications	Sinus tract, fistula, strictures, fibrosis	Architectural distortion of glands, branching, Paneth cell metaplasia
Special Features	Creeping fat on mesenteric side	Lead pipe appearance on barium (in long-standing cases)
Distribution	30-50% have disease affecting both ileum and colon; 30% have isolated small bowel (terminal ileum); isolated jejunal, stomach or duodenal involvement is rare	45% have proctitis; 35% have left-sided colitis; 20% have pancolitis; more severe distally; continuous and symmetric is hallmark; backwash ileitis in pancolitis

Chrons disease with cobblestoning and deep serpigenous linear ulcers

Montreal Classification of Inflammatory Bowel Disease

Answer: A

Explanation:

For the given case:

• The patient is 35 years old: A2
• The disease involves both the ileum and colon: L3
• There is a stricture in the mid-ileum with a fistulous communication with the sigmoid colon, indicating a penetrating disease: B3
• There is an anal fistula: p (perianal disease modifier)

Thus, the classification is A2L3B3p.

MCQ - Screening for Development of Colorectal Neoplasia in Inflammatory Bowel Disease

Answer: B

Explanation:

• Pancolitis: Screening should begin 8 years after the onset of colitis.
• Left-sided colitis: Screening should begin 12-15 years after the onset of colitis.
• For general colitis without specifying pancolitis or left-sided colitis, screening should start 10 years from the onset of colitis.

Additional notes on disease activity and management:

• Disease activity: More severe in pancolitis compared to left-sided colitis.
• Screening protocol:
  • Pancolitis: Start screening 8 years after onset.
  • Left-sided colitis: Start screening 12-15 years after onset.
• PSC (Primary Sclerosing Cholangitis): Patients with IBD and PSC may need earlier and more frequent screenings due to higher cancer risk.
• At least 32 biopsy specimens should be obtained during screening colonoscopy.
• High-grade dysplasia: Requires a second opinion; if confirmed, proctocolectomy is recommended.
• DALM (Dysplasia-Associated Lesion or Mass): Proctocolectomy is recommended due to a 50% risk of malignancy.
• Risk of malignancy: 2% at 10 years, 8.5% at 20 years, and 17% at 30 years after the onset of colitis.

MCQ - True Love and Witts Criteria for Ulcerative Colitis

Answer: D

Explanation:

The True Love and Witts Classification is used to assess the severity of Ulcerative Colitis (UC) based on clinical parameters, not endoscopic findings. The criteria include:

• Mild:
  • Less than 4 stools/day, with or without small amounts of blood
  • No fever
  • No tachycardia
  • Mild anemia
  • ESR less than 30 mm/hr
• Moderate:
  • Intermediate between mild and severe
• Severe:
  • More than 6 stools/day, with blood
  • Fever more than 37.5°C
  • Heart rate more than 90/min
  • Anemia with Hgb level less than 75% of normal
  • ESR more than 30 mm/hr

The criteria focus on stool frequency, ESR (erythrocyte sedimentation rate), hemoglobin levels, and vital signs such as fever and heart rate. Endoscopy is not included in the True Love and Witts criteria for assessing UC severity.

MCQ - Extraintestinal Manifestations in Inflammatory Bowel Disease (IBD)

Answer: A

Explanation:

• Extraintestinal manifestations are more common in Crohn's disease than in Ulcerative colitis.
• The most common extraintestinal manifestation in Ulcerative colitis is arthritis.
• Primary sclerosing cholangitis (PSC) has a course that is independent of bowel activity in UC.
• PSC increases the risk of colonic neoplasia and the risk of pouchitis in UC.

Summary of Extraintestinal Symptoms:

• Crohn's disease > Ulcerative colitis for extraintestinal manifestations.
• Most common manifestation: Arthritis. (20%)
• Independent of bowel activity: Ankylosing spondylitis, PSC.
• Cutaneous manifestations (10%): Erythema nodosum and pyoderma gangrenosum (treated with systemic steroids and biologics).
• Ocular manifestations(5%) : Uveitis, iritis, and episcleritis.
• PSC:
  • Occurs in about 5% of IBD cases.
  • More common in Ulcerative colitis than Crohn's disease.
  • Increases the risk of colorectal neoplasia.
  • Increases the risk of pouchitis.

Management of UC and Crohn’s Disease:

MCQ - Induction and Maintenance of Remission in Both UC and Crohn's Disease

Answer: C

Explanation:

• Mesalamine: Used in mild to moderate UC for both induction and maintenance of remission.
• Corticosteroids: Used in both UC and Crohn's disease for induction of remission but not for maintenance.
• Infliximab: Used in both UC and Crohn's disease for both induction and maintenance of remission.
• Azathioprine: Used for maintenance of remission but not typically for induction.

Therapies for Crohn’s Disease

Note: Ciprofloxacin and metronidazole do not heal fistulas but reduce fistula drainage and are used as adjuncts to anti-TNF-α agents.

Combination Therapy:

• Anti-TNF-α therapy combined with a thiopurine or methotrexate is more efficacious than anti-TNF-α monotherapy in inducing and maintaining remission in CD. The addition of methotrexate probably also increases the efficacy of anti-TNF-α induction by decreasing immunogenicity. No maintenance data are available, but the combination of an immunomodulator (thiopurine or methotrexate) and anti-TNF-α is probably more effective than anti-TNF-α monotherapy in maintaining remission.

Risk Stratification and Medical Therapy for Inflammatory Luminal Crohn Disease

Answer: D

Explanation:

1. Risk Stratification:
   • Current Inflammatory Burden:
     • The patient presents with:
       • Fever, weight loss, joint pains: Indicators of high inflammatory burden.
       • Severe anemia: Confirms high inflammatory burden.
       • Deep ulcers on endoscopy: Further indicates severe disease.
   • Long-Term Burden:
     • Age at diagnosis is 35 years.
     • The long-term risk factors need assessment, but with severe symptoms and deep ulcers, a high-risk categorization is likely.
2. Risk Stratified Therapy:
   • Low-Risk Patients:
     • Options include:
       • Course of budesonide or prednisone, with or without AZA for disease of the terminal ileum or proximal colon.
       • Course of prednisone, with or without AZA for disease of the left colon or entire colon.
   • High-Risk Patients:
     • Options include:
       • Anti-TNF-α monotherapy.
       • Anti-TNF-α plus thiopurine.
       • Ustekinumab.
       • Vedolizumab.
3. Most Appropriate Initial Therapy:
   • Given the patient's high inflammatory burden (severe symptoms, severe anemia, and deep ulcers), they fall into the high-risk category.
   • The optimal therapy for high-risk patients with active inflammation includes Anti-TNF-α plus thiopurine.
   • The combination therapy is preferred for its higher efficacy in inducing remission and improved durability due to suppression of anti-drug antibodies.

Conclusion:

For a 35-year-old patient with severe symptoms of Crohn's disease and high inflammatory burden, the most appropriate initial therapy would be Anti-TNF-α plus thiopurine. This approach targets the aggressive disease effectively, aligning with the risk stratified therapy recommendations. Thus, the correct answer is D.

Therapies for Ulcerative Colitis

Induction of Remission:

• Mesalamine: For mild to moderate UC.
• Steroids:
  • Budesonide: Mild to moderate UC.
  • Prednisone: Moderate UC.
  • IV steroids: Severe UC.
• Cyclosporine [ Rescue therapy ]: Severe UC after failure of IV steroids.
• Thiopurines (Azathioprine, Mercaptopurine): No efficacy in induction. used in combination with Anti TNF- α
• Anti-TNF-α (Infliximab, Adalimumab, Golimumab):
  • Moderate UC (first-line therapy).
  • Moderate UC that is steroid-dependent or steroid-refractory, or has failed thiopurine.
  • Infliximab: Severe UC (first-line therapy or after failure of IV steroids).
• Vedolizumab:
  • Moderate UC (first-line therapy).
  • Moderate UC that is steroid-dependent, or steroid-refractory, or has failed thiopurine or anti-TNF-α.

Maintenance of Remission:

• Mesalamine:
  • After successful induction with mesalamine or budesonide.
• Thiopurines:
  • Maintenance of remission induced by prednisone, IV steroids, or IV cyclosporine.
• Anti-TNF-α:
  • After successful anti-TNF-α induction.
• Vedolizumab:
  • After successful vedolizumab induction.

No Role of Steroids and Cyclosporine in Maintenance of remission.

Vedolizumab for Moderate UC Adali and Golimumab are used for Moderate or steroid refractory or dependent INFLIXIMAB for SEVERE UC

Risk oriented Medical Therapy of Ulcerative Colitis

Answer: C

Explanation:

1. Severity Assessment:
   • The patient has severe ulcerative colitis as indicated by the lack of response to first-line IV steroids.
2. Induction Therapy for Severe Disease:
   • First-line: IV steroids are typically used as the initial approach for severe UC.
   • Next Steps After Failure of IV Steroids:
     • Infliximab: Recommended as either a first-line or second-line option following the failure of IV steroids.
     • Cyclosporine: Considered after the failure of first-line IV steroids, but typically not the first choice after IV steroids.
   • Options:
     • Infliximab (C): Anti-TNF-α agent, effective in inducing remission in severe UC.
     • Cyclosporine: Alternative option but usually considered after anti-TNF agents in the escalation pathway.
3. Comparison of Options:
   • Oral 5-ASA (A): Suitable for mild to moderate disease, not appropriate for severe UC.
   • Budesonide (B): Used for moderate disease, not severe UC.
   • Oral 5-ASA with Rectal 5-ASA (D): Combination used for mild to moderate disease, not severe UC.
4. Maintenance Therapy:
   • Once remission is achieved with agents like infliximab, maintenance therapy can include:
     • Thiopurine.
     • Anti-TNF-α (with or without thiopurine).
     • Vedolizumab.

Conclusion:

For a patient with severe ulcerative colitis not responding to first-line IV steroids, the next best step in management is to initiate Infliximab. This approach aligns with evidence-based recommendations for induction therapy in severe UC following the failure of initial IV steroid treatment. Thus, the correct answer is C.

MCQ - Management of Acute Severe Ulcerative Colitis

Answer: D

Explanation:

In the context of managing acute severe ulcerative colitis:

• Infliximab: Used for severe UC, both as first-line therapy or after failure of IV steroids.
• Cyclosporine: Used in severe UC after failure of IV steroids.
• Infliximab + Azathioprine: Combined therapy is often used to induce and maintain remission, especially in steroid-dependent or refractory cases.
• Azathioprine: Not effective in the induction of remission for acute severe UC. It is used for maintenance of remission after induction with other agents but not effective for acute severe UC.

According to the provided context:

• Induction of Remission: Infliximab and cyclosporine are used for severe UC. Azathioprine alone is not used for induction but is effective for maintenance.
• Maintenance of Remission: Azathioprine is effective after induction of remission but not for acute severe cases.

Thus, Azathioprine is not used for the management of acute severe ulcerative colitis, aligning with the answer

In the management of acute severe ulcerative colitis, the focus is on achieving rapid control of inflammation with agents like IV steroids, infliximab, and cyclosporine. Azathioprine is used for maintaining remission once the acute phase is controlled, but not for the initial management of an acute severe flare.

Indications for surgery for UC:

• Steriod dependent
  • Failure to decrease the dose of steroid after 6 weeks of steroid usage
• Steriod refractory / resistant
  • No effect after 2 weeks prednisolone or 1 week of IV Hydrocortisone
• Acute severe ulcerative colitis
• Toxic megacolon
• Dysplasia and Malignancy

Case Scenario’s of ASUC:

Case 1:

Answer: D

Explanation:

• IV Steroids: Cornerstone of treatment for acute severe UC. Hydrocortisone 100 mg every 6 hours is commonly used.
• UFH: UC is a procoagulant state, so anticoagulation with UFH is recommended to prevent thromboembolic complications.
• Infliximab: Can be used for induction in severe UC as it helps in achieving remission.
• Opioids: Absolutely contraindicated in UC as they can precipitate toxic megacolon.

Management of ASUC:

• Hydration and correction of electrolytes.
• Avoid NSAIDs, opioids, and anticholinergic drugs (can cause megacolon).
• Enteral nutrition.
• No evidence for bowel rest with TPN (except in toxic megacolon).
• Anticoagulation: To prevent thromboembolism.
• Antibiotics: Have not shown benefit, but ciprofloxacin and metronidazole may be used.
• Blood transfusion: If Hb < 10.
• Regular physical examination, vitals monitoring, stool charting, and serial CBC, CRP, and KFT.

Case 2:

Answer: A

Explanation:

• IV Hydrocortisone or Methylprednisolone:
  • Standard initial treatment.
  • Steriods (methylprednisolone 60 mg/day) or hydrocortisone 100 mg every 6 hourly 6-10 days.
  • If no response by day 3, a change to another steroid is not beneficial.
• Infliximab:
  • Used as rescue therapy for those not responding to initial steroid treatment.
  • you have to screen for Latent infections like HBV, TB , Histoplasmosis before starting on infliximab.
• Cyclosporine: Another option for rescue therapy if not responding to steroids.
• Consider surgery: If medical management fails, surgery might be needed.

Steroid Response Evaluation:

• Response rate: 70%.
• Evaluation on day 3:
  • Stool >8 or 3-8 with CRP >45: Non-responder.
  • Stool 3-8 and CRP <45: Incomplete responder.
  • Stool <3: Complete responder.
• Rescue Therapy:
  • Medical Rescue Therapy : Cyclosporine(2 mg/kg/day) or infliximab (5 mg/kg/day).
  • Surgical Rescue Therapy : Do not go beyond Day 5

Both cyclosporine and infliximab have similar efficacy and are chosen based on the patient's side effect profile.

• Cyclosporine: Used as rescue therapy and can be considered as first-line therapy in place of steroids in certain cases of UC.
  • Efficacy: Same as infliximab.
  • Dosage: 2 mg/kg/day.
  • 80% avoid Colectomy
  • Prophylaxis: Against Pneumocystis jiroveci.
  • Side Effects: Nephrotoxicity, hypertension, hyperkalemia, hypomagnesemia, hyperlipidemia, hirsutism, tremor, seizure. [Hypomagnesemia and Hypocholesterolemia.]
  • Note: Not used for maintenance therapy.

Case3:

Answer: B

Explanation:

When infliximab as a rescue therapy shows no response by day 5, further management should focus on alternative diagnoses, potential complications, and preparation for surgical intervention if necessary.

• Rule out CMV colitis: CMV infection can cause or exacerbate colitis in UC patients. It should be ruled out if there is no response to standard therapies.
• Switch to cyclosporine: Switching to cyclosporine after infliximab failure is not typically recommended. Both drugs have similar efficacy and are usually not sequentially used after the failure of one.
• Plan for emergency surgery: If the patient does not respond to medical therapy, planning for emergency surgery is essential. Delaying surgery beyond 5 days in acute severe UC increases morbidity and mortality.
• CECT chest along with Montoux test before starting infliximab: This is necessary to screen for latent infections such as TB before initiating infliximab. Infliximab and other anti-TNF-α therapies increase the risk of reactivating latent infections like TB and hepatitis B.

Additional Context on Anti-TNF-α Therapy and Timing of Surgery

Anti-TNF-α Therapy:

• Drugs: Infliximab (chimeric monoclonal antibody), Adalimumab, Golimumab (humanized antibodies).
• Indications: Moderate to severe UC, steroid-dependent, or steroid-refractory disease.
• Long-term Efficacy: Often compromised due to the formation of anti-drug antibodies (ADA). Combining with methotrexate or azathioprine decreases ADA formation.
• Screening Before Therapy: Essential to screen for latent infections like TB and hepatitis B before starting anti-TNF-α therapy.
• Side Effects: Infusion reactions, hepatotoxicity, demyelination (e.g., multiple sclerosis, optic neuritis), increased risk of bacterial, mycobacterial, and fungal infections.

Vedolizumab:

• Mechanism: (α4β7) integrin inhibitor that prevents lymphocyte trafficking in the gut, reducing the risk of TB activation.

Timing of Surgery:

• Acute Severe UC: Delaying surgery beyond 5 days increases morbidity and mortality.
• Toxic Megacolon: Surgery should be planned within 24-48 hours if the patient is not improving.

MCQ - Appropriate Surgical Procedure for Toxic Megacolon in UC

Answer: D

Explanation:

Toxic megacolon is a severe complication of ulcerative colitis that requires prompt surgical intervention if medical management fails. The appropriate surgical procedures in the setting of toxic megacolon differ from those used in elective settings due to the acute nature of the illness and the need to stabilize the patient quickly.

Toxic Megacolon Criteria:

1. HR > 100
2. TLC > 12,000
3. Albumin < 3.5
4. Temperature > 38°C
5. Transverse colon diameter > 5 cm
6. Presence of any three of the above criteria.

Surgical Management of Toxic Megacolon:

• Initial Management:
  • IV steroids.
  • Early surgery if not responding within 24-48 hours.
• Appropriate Surgical Procedures:
  • Subtotal Colectomy with End Ileostomy: The preferred procedure for acutely ill patients. It involves removing the colon while leaving the rectum, with an end ileostomy created for fecal diversion.
  • Loop Ileostomy: For very sick patients who may not tolerate extensive surgery.
  • Tube Cecostomy (Blow Hole Cecostomy): For decompression in critically ill patients.
• Inappropriate Surgical Procedures in Acute Setting:
  • Total Colectomy with Ileorectal Anastomosis: Not appropriate in acute settings due to the high risk of complications and the need for bowel rest.
  • Total Proctocolectomy with End Ileostomy: Too extensive for the acute setting.
  • Total Proctocolectomy with IPAA (Ileal Pouch-Anal Anastomosis): Not appropriate in the acute setting as it involves creating an ileal pouch and anastomosing it to the anus, which is complex and better suited for elective surgery when the patient is stabilized and not on high doses of steroids or biologics.

Elective Surgical Options for UC:

1. Subtotal Colectomy + End Ileostomy and Hartmann's Procedure.
2. Total Proctocolectomy + End Ileostomy.
3. Total Proctocolectomy + Ileal Pouch-Anal Anastomosis (IPAA): The treatment of choice in elective settings.
4. Subtotal Colectomy + Ileorectal Anastomosis.
5. No Role for Segmental Colectomy.

IPAA (Ileal Pouch-Anal Anastomosis):

• Removes the entire colon and at-risk mucosa while preserving continence.
• Various types of pouches (J-pouch, S-pouch, W-pouch) are used.
• Pouch Stages:
  • One-stage: [Total proctocolectomy + IPAA without ileostomy].
  • Two-stage: [Total proctocolectomy + IPAA with ileostomy] + [ileostomy closure].
  • Three-stage: [Subtotal colectomy + end ileostomy] + [IPAA + ileostomy] + [ileostomy closure].
  • Modified two-stage: [Subtotal colectomy + end ileostomy] + [IPAA].
• Stage Selection:
  • One and two-stage procedures are done in elective settings.
  • Modified two-stage and three-stage procedures are used in emergency settings.

In summary, the correct approach in an acute setting, such as toxic megacolon, focuses on stabilizing the patient and avoiding complex surgeries like total proctocolectomy with IPAA. The preferred procedures are subtotal colectomy with end ileostomy or, in very sick patients, loop ileostomy or tube cecostomy.

MCQ - Pouchitis Disease Activity Index and Management

Answer: C

Explanation:

Risk Factors for Pouchitis:

• Ulcerative Colitis (UC): Pouchitis is more commonly seen in patients with UC compared to Familial Adenomatous Polyposis (FAP).
• Primary Sclerosing Cholangitis (PSC): A known risk factor for pouchitis.
• Age: Older age increases the risk of developing pouchitis.
• Smoking: Not a risk factor; in fact, non-smoking status is a risk factor.
• NSAIDs: Use of NSAIDs can increase the risk of pouchitis.

Pouchitis Disease Activity Index (PDAI):

• Pouchitis is defined as a total score greater than 7 points.

  Management of Pouchitis:

  • Antibiotics:
    • Ciprofloxacin and Metronidazole: Typically used for 14 days.
    • Cyclic courses of antibiotics: May be necessary for recurrent cases.
  • Probiotics:
    • VSL-3: Used to prevent recurrence of pouchitis.
  • Steroids:
    • Budesonide suppository: Can be used in the management of pouchitis.

  Additional Notes:

  • Mobilization of Pouch:
    • Mobilization of the small bowel mesentery up to the pancreas is important.
    • Ileocolic vessels should be preserved during colectomy.
    • Scoring of the mesentery (peritoneal windowing) and division of the ileocolic pedicle are essential steps.
    • The pouch should be left intact during mobilization.

MCQ - Chronic Antibiotic-Refractory Pouchitis (CARP)

Answer: B

Explanation:

Characteristics and Management of CARP:

• Chronic Antibiotic-Refractory Pouchitis (CARP):

  • Uncommon Condition: CARP is not common and can indicate other underlying issues.
  • Underlying Causes: May include viral infections (e.g., Cytomegalovirus), structural/functional pathologies (e.g., fistula, ischemia, stricture), or autoimmune-mediated diseases.
  • Fecal Bacterial Culture: A good first measure for pouchitis refractory to commonly used empiric antibiotics.
  • Cytomegalovirus Infection: Should be evaluated and treated with antiviral ganciclovir therapy.
  • Clostridium Difficile Infection: Requires treatment with oral metronidazole or vancomycin.
  • NSAID Use: Should be excluded as a contributing factor.
  • Immune-Mediated Pouchitis: A newly described disorder that may underlie CARP.
  • Association with Autoinflammatory Disorders: There is a noted association with primary sclerosing cholangitis and autoimmune thyroid disease.

  Treatment Options:

  • Empiric Treatment:
    • Topical or systemic corticosteroids.
    • Immunomodulators.
    • Anti-TNF-α agents such as infliximab.
    • Infliximab: Shown to be effective in treating chronic refractory pouchitis and related complications. In a study, 88% of patients with refractory luminal inflammation showed clinical response, and 86% showed fistula response.

  Other Related Conditions:

  • Prepouch Ileitis:
    • Concurrent with Pouchitis: Diagnosed in 5.7% of patients undergoing pouchoscopy.
    • Clinical Implications: Unknown, but does not imply missed Crohn’s disease or increase the risk of pouch failure.
    • Combination Antibiotic Therapy: Effective in reducing the length of prepouch inflammation and inducing symptomatic remission (e.g., Ciprofloxacin and Metronidazole).
  • Irritable Pouch Syndrome:
    • Functional Disorder: Causes symptoms in the absence of structural or inflammatory abnormalities of the pouch.
    • Symptoms: Similar to irritable bowel syndrome, including visceral hypersensitivity, sensation of gas, urge to defecate, and pain.

Summary:

Chronic antibiotic-refractory pouchitis (CARP) is an uncommon condition often associated with underlying viral infections, structural/functional pathologies, or autoimmune-mediated diseases. It requires comprehensive evaluation and treatment, including the use of antiviral therapy for viral infections, exclusion of NSAID use, and the use of corticosteroids, immunomodulators, or anti-TNF-α agents for immune-mediated cases. Combination antibiotic therapy is effective for concurrent prepouch ileitis, and irritable pouch syndrome requires management similar to other functional gastrointestinal disorders.

---

MCQ - Diverticular Disease

Answer: A

Explanation:

Diverticular Disease Overview:

• True Diverticula:
  • Rare, congenital.
  • Involve all layers of the bowel wall.
• False Diverticula:
  • More common, known as pulsion diverticula.
  • Involve only the mucosa and submucosa.
  • Typically caused by increased intraluminal pressure.
• Risk Factors:
  • Western diet, obesity, smoking.
• Common Sites:
  • Sigmoid and descending colon.
  • Rectum is usually spared.
• Diverticulitis:
  • Occurs in about 5% of cases with diverticulosis.

Investigation of Choice for Colovesical Fistula:

• CECT Abdomen:
  • The investigation of choice for detecting diverticulitis and colovesical fistula.
  • Indicative sign: air in the bladder.
• Cystoscopy:
  • Visualizes the fistula, but not the first-line investigation.
• Barium Enema:
  • Not typically used for diagnosing colovesical fistula in the acute phase.
• Sigmoidoscopy:
  • Not done in the acute phase of diverticulitis.
  • Used to rule out underlying carcinoma once the acute phase is resolved.

Segmental Colitis Associated Diverticulosis (SCAD):

• Characteristics:
  • More common in males.
  • Symptoms: pain with diarrhea, tenesmus, and hematochezia.
  • Colonoscopy findings: granular and friable mucosa, ulceration on the crest of colonic folds.
  • Rectum remains normal.
  • Biopsy findings: focal chronic colitis with crypt abscesses and lymphomononuclear infiltration of the lamina propria.

Symptomatic Uncomplicated Diverticular Disease (SUDD):

• Characteristics:
  • Chronic low-grade symptoms.
  • Mimics IBS with the presence of diverticulosis.

Summary:

In the context of diverticular disease, particularly for detecting complications such as colovesical fistula, CECT abdomen is the investigation of choice due to its ability to reveal air in the bladder and other relevant details. Other investigations like cystoscopy, barium enema, and sigmoidoscopy have specific roles but are not the first-line investigations for acute complications. Additionally, understanding conditions like SCAD and SUDD is crucial for comprehensive management of patients with diverticular disease.

Modified Hinchey Classification:

Answer: A

Explanation:

• Based on the Modified Hinchey Classification:
  • Stage 0: Mild clinical diverticulitis
  • Stage 1a: Confined pericolic inflammation - phlegmon
  • Stage 1b: Confined pericolic abscess (within sigmoid mesocolon)
  • Stage II: Pelvic, distant intra-abdominal, or retroperitoneal abscess
  • Stage III: Generalized purulent peritonitis
  • Stage IV: Fecal peritonitis

For Stage 0 & 1a, the treatment typically involves antibiotics and supportive care.

Related Trials:

• DIVER trial: Hospitalization versus outpatient management in uncomplicated diverticulitis.
• AVOD trial: Antibiotics versus no antibiotics in inpatients with uncomplicated diverticulitis.

Follow-up Management:

Answer: A

Explanation:

• For uncomplicated diverticulitis (Stage 0 and 1a), the management includes dietary modifications and follow-up with sigmoidoscopy. Surgery is not immediately indicated unless there are recurrent episodes or other complications.

Complicated Diverticulitis:

Answer: A

Explanation:

• Complicated diverticulitis with a pelvic abscess <4 cm can often be managed with antibiotics alone. Abscesses >4 cm typically require antibiotics and percutaneous drainage.

Case of Perforation:

Answer: B

Explanation:

• Purulent peritonitis: Typically managed with laparoscopic lavage.

  Role of laparoscopic lavage for purulent peritonitis:

  • SCANDIV trial: Lavage leads to worse outcomes.
  • LOLA trial: Increased complications in the lavage group.
  • DILALA trial: Positive trial favoring laparoscopic lavage.
  • Feculent peritonitis: Indicated by free extraluminal air, managed with Hartman's procedure (resection of the affected segment with end colostomy).

Summary of Diverticular Disease Management:

Management Based on Severity:

• Uncomplicated Diverticulitis (Stage 0 and 1a):
  • Dietary modification
  • Pain medications
  • Antibiotics (based on clinical judgment)
  • Sigmoidoscopy should be done on follow up
  • Surgery is considered if there are recurrent episodes or complications.
  • Related Trials: DIVER trial, AVOD trial.

• Complicated Diverticulitis (Stages 1b to IV):

  • High-risk features on CT include fistula, abscess, perforation, extraluminal air/contrast.
  • Surgery: Sigmoid resection (laparoscopic or open).
    • Most common cause of recurrence is inadequate distal margin.

  Specific Complications:

  • Abscess:
    • <4 cm: Managed with antibiotics.

    • 4 cm: Managed with antibiotics and percutaneous drainage.

    • Elective resection recommended for pelvic abscess.
  • Fistula:
    • Most common site: colovesical (dome of bladder).
    • Symptoms: pneumaturia and fecaluria.
    • Diagnosis: CT with contrast, cystoscopy.
    • Management: Dismantling and resection of the bowel.
  • Perforation:
    • Purulent peritonitis: Typically managed with laparoscopic lavage. Refer to SCANDIV, LOLA, and DILALA trials for more details.
    • Feculent peritonitis: Managed with Hartman's procedure (anastomosis with diverting ileostomy).

Right-Sided Diverticulitis:

• More common in Asian countries and younger patients.
• Typically managed with right hemicolectomy.