crohn's Disease

Crohn’s disease

Chronic, transmural (affecting the entire thickness of the bowel wall) inflammatory disorder that can affect any part of the gastrointestinal tract from the mouth to the an*s, though the terminal ile*m and col*n are the most common sites.

Distribution: "Skip Lesions"

(healthy tissue interspersed between inflamed areas)

Depth of Inflammation: Transmural

(penetrates through the mucosa, submucosa, and muscularis layers). This leads to complications like strictures, fistulas, and abscesses.

Endoscopic Appearance: "Cobblestone"

due to deep longitudinal ulcerations alongside normal or edematous mucosa.

Microscopic Hallmark: Non-caseating granulomas

(seen in about 30–50% of biopsies; highly specific for Crohn’s compared to UC).

Clinical Presentation

• Chronic, non-bloody diarrhea (unlike UC, where bloody diarrhea is classic).

• Right lower quadrant (RLQ) abdominal pain and cramping (due to terminal ileum involvement).

• Significant weight loss, malabsorption, and nutritional deficiencies (especially Vitamin B12 and fat-soluble vitamins, since the terminal ile*m absorbs B12-intrinsic factor complexes and bile salts).

• Extraintestinal manifestations: Arthralgia/arthritis, eye inflammation (uveitis/episcleritis), and skin lesions (erythema nodosum, pyoderma gangrenosum).

Mild-to-Moderate Disease (Induction & Maintenance)

5-Aminosalicylates (5-ASAs) / Aminosalicylates

Oral Corticosteroids (Induction Only)

5-Aminosalicylates (5-ASAs) / Aminosalicylates

• Agents: Mesalamine (Asacol, Pentasa, Lialda), Sulfasalazine, Balsalazide.

• Mechanism: Act locally in the gut lumen to inhibit prostaglandin and leukotriene synthesis.

_{^{PhLE Pearl: 5-ASAs are much more effective in Ulcerative Colitis than in Crohn's disease. However, Pentasa (which releases mesalamine throughout the small intestine and colon) or targeted mesalamine formulations are sometimes used for mild ileocolonic Crohn's. Sulfasalazine requires bacterial cleavage by colonic flora into sulfapyridine and 5-ASA.}}

Oral Corticosteroids (Induction Only)

• Agents: Prednisone or Methylprednisolone.

• Role: Used strictly for short-term induction of remission in acute flares. Never use corticosteroids for maintenance, as they have no efficacy in keeping the disease in remission and cause severe long-term toxicity (osteoporosis, Cushingoid features, infection risk).

• _{^{Alternative: Budesonide (Entocut EC). A high-affinity glucocorticoid with extensive first-pass hepatic metabolism (low systemic bioavailability). Ideal for mild-to-moderate ileocecal Crohn's disease because it treats local inflammation with minimal systemic side effects.}}

Moderate-to-Severe Disease (Immunomodulators & Biologics)

_{^{When patients fail 5-ASAs or are steroid-dependent, therapy must be escalated.}}

Thiopurines (Immunomodulators)

Anti-Tumor Necrosis Factor (Anti-TNF) Biologics

Integrin Receptor Antagonists (Gut-Selective Biologics)

Interleukin-12/23 Inhibitors

JAK Inhibitors

Thiopurines (Immunomodulators)

• Agents: Azathioprine and Mercaptopurine (6-MP).

• Role: Used for maintenance of remission and as steroid-sparing agents. Onset of action is slow (takes 3 to 6 months).

• _{^{Pharmacogenetics Warning: Before starting azathioprine, patients should ideally be tested for TPMT (Thiopurine S-methyltransferase) enzyme activity. Patients with low or deficient TPMT activity are at risk of life-threatening, profound myelosuppression (bone marrow failure).}}

Anti-Tumor Necrosis Factor (Anti-TNF) Biologics

• Agents: Infliximab (IV), Adalimumab (SC), Certolizumab pegol (SC).

• Role: Highly effective for inducing and maintaining remission, healing mucosal tissue, and closing fistulas (especially Infliximab for perianal fistulizing Crohn's).

• _{^{Screening Requirement: Prior to initiating any anti-TNF biologic, patients must be screened for Latent Tuberculosis (TB) via a Tuberculin Skin Test (TST / PPD) or Interferon-Gamma Release Assay (IGRA), because anti-TNF agents destroy granulomas and can cause reactivation of disseminated TB.}}

Integrin Receptor Antagonists (Gut-Selective Biologics)

• Agent: Vedolizumab (Entyvio).

• Mechanism: Monoclonal antibody that blocks alpha4 beta7 integrin, preventing white blood cells from migrating into the gut tissue.

• _{^{Advantage: Gut-selective, meaning it has a lower risk of systemic infections or central immunosuppression compared to anti-TNFs.}}

Interleukin-12/23 Inhibitors

Agent: Ustekinumab (Stelara). Blocks IL-12 and IL-23 pathways, approved for moderate-to-severe Crohn's disease refractory to other agents.

JAK Inhibitors

Agent: Upadacitinib (oral small molecule). Approved for moderately to severely active Crohn's disease. Boxed warnings include serious infections, thrombosis, and major adverse cardiac events (MACE).

Surgical Management & Pharmacist's Role

_{^{Unlike Ulcerative Colitis (which can be "cured" by a total colectomy), surgery is NOT a cure for Crohn's disease.}}

• Because Crohn's is transmural and affects the entire GI tract, inflammation frequently recurs at the surgical anastomotic sites (where healthy bowel ends are sewn back together)

Post-Operative Management

Smoking cessation is the single most important lifestyle modification because cigarette smoking dramatically increases the recurrence rate and need for repeat surgery in Crohn's patients. Maintenance therapy with thiopurines or anti-TNFs is often initiated post-surgery to prevent recurrence.