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    Subjects/Pathology/Crohn Disease and Ulcerative Colitis — Comparative Pathology
    Crohn Disease and Ulcerative Colitis — Comparative Pathology
    hard
    microscope Pathology

    A 35-year-old woman from Mumbai presents with a 3-month history of chronic diarrhoea, perianal fistulae, and abdominal pain localised to the right lower quadrant. Colonoscopy shows patchy areas of inflammation with normal intervening mucosa ('skip lesions') extending from the terminal ileum into the caecum. Biopsy reveals transmural inflammation with non-caseating granulomas in the submucosa and muscularis propria. She has already failed mesalamine 2.4 g/day and a 6-week course of prednisolone (now steroid-dependent). What is the most appropriate next step in management?

    A. Start azathioprine 2–2.5 mg/kg/day and continue prednisolone at maintenance dose
    B. Increase prednisolone dose to 60 mg/day and extend taper over 12 weeks
    C. Refer for elective ileocaecal resection
    D. Initiate infliximab 5 mg/kg induction (weeks 0, 2, 6) and taper prednisolone

    Explanation

    ## Clinical Diagnosis: Crohn Disease This patient has **Crohn disease (CD)** confirmed by: - Skip lesions (patchy inflammation with normal intervening mucosa) - Transmural inflammation (extends through all bowel wall layers) - Non-caseating granulomas (pathognomonic for CD) - Perianal fistulae (CD-specific complication) - Ileocaecal involvement (most common site) ## Key Management Principle: Steroid-Dependent Disease **High-Yield:** The patient is **steroid-dependent** (requires prednisolone to maintain remission after a 6-week course). This is the critical trigger for escalation to **biologic therapy** (TNF-α inhibitor). **Key Point:** Steroid-dependent Crohn disease requires immunosuppression or biologic therapy to: 1. Induce and maintain remission 2. Reduce steroid requirement and toxicity 3. Prevent complications (fistulae progression, strictures) ## Management Algorithm for Steroid-Dependent Crohn Disease ```mermaid flowchart TD A[Crohn Disease]:::outcome --> B{Response to induction steroids?}:::decision B -->|Yes, remission| C[Assess steroid-dependence]:::decision C -->|Steroid-independent| D[5-ASA or mesalamine maintenance]:::action C -->|Steroid-dependent| E[Escalate to immunosuppression]:::action E --> F{Fistulizing disease?}:::decision F -->|Yes| G[TNF-inhibitor: Infliximab]:::action F -->|No| H[Azathioprine or TNF-inhibitor]:::action B -->|Steroid-refractory| I[TNF-inhibitor or surgery]:::action G --> J[Taper prednisolone]:::action H --> K[Taper prednisolone]:::action ``` ## Why Infliximab Is Correct | Criterion | Azathioprine | Infliximab | |-----------|--------------|------------| | **Onset** | 8–12 weeks | 2–4 weeks | | **Steroid-dependent CD** | Second-line option | **First-line** | | **Fistulizing CD** | Not effective | **Highly effective** | | **Transmural disease** | Moderate efficacy | **Superior efficacy** | | **Remission induction** | No | **Yes** | **Clinical Pearl:** Infliximab is particularly indicated in this patient because: 1. She has **fistulizing disease** (perianal fistulae) — TNF-α inhibitors are the only agents proven to close fistulae in CD 2. She is **steroid-dependent** — requires biologic therapy to allow steroid withdrawal 3. She has **transmural inflammation** — TNF-α inhibitors penetrate all layers and reduce transmural complications ## Infliximab Induction Protocol - **Dose:** 5 mg/kg IV infusion - **Schedule:** Weeks 0, 2, and 6 (induction phase) - **Maintenance:** 5 mg/kg every 8 weeks (after week 14) - **Concurrent therapy:** Continue mesalamine; taper prednisolone by 5 mg every 1–2 weeks **Mnemonic:** **FIST** = **F**istulizing disease, **I**mmune-mediated complications, **S**teroid-dependent, **T**ransmural → TNF-inhibitor ## Why Not the Other Options? **Option 1 (Increase prednisolone):** Increasing steroid dose in steroid-dependent disease is counterproductive: - Increases toxicity (osteoporosis, infections, hyperglycaemia) - Does not address underlying pathology - Prolongs steroid dependence - Guideline-discordant **Option 2 (Azathioprine monotherapy):** While azathioprine can be used for steroid-dependent CD, it: - Takes 8–12 weeks to work (slow onset) - Is less effective than TNF-inhibitors for fistulizing disease - Does not induce remission as rapidly - Is typically second-line after TNF-inhibitor failure or in combination with TNF-inhibitors **Option 4 (Surgery):** Ileocaecal resection is curative for localized disease but: - Is not first-line for steroid-dependent disease - Should be reserved for complications (strictures, perforation, intractable disease despite medical therapy) - This patient has not yet failed biologic therapy ![Crohn Disease and Ulcerative Colitis — Comparative Pathology diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/16285.webp)

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