Mucositis

Definition

• Inflammation and ulceration of the oral and/or GI mucosa due to chemotherapy or radiation.
• Affects rapidly dividing epithelial cells in the GI tract.
• Can involve: mouth (oral mucositis), pharynx, esophagus, stomach, intestines.

Pathophysiology

1. Initiation: Chemotherapy → DNA damage in epithelial basal cells.
2. Upregulation: Inflammatory cytokines (TNF-α, IL-1, IL-6) released.
3. Amplification: Further tissue injury and ulceration.
4. Ulceration phase: Painful lesions, bacterial colonization → infection risk.
5. Healing phase: Re-epithelialization after drug clearance.

Causative Agents (High Risk)

• Antimetabolites: Methotrexate, 5-FU, Capecitabine, Cytarabine.
• Alkylators: Melphalan (esp. high-dose conditioning for HSCT).
• Anthracyclines: Doxorubicin.
• Others: mTOR inhibitors (everolimus, temsirolimus), radiation.

Clinical Features

• Onset: 5–10 days after chemo start.
• Symptoms: Erythema → painful ulcers, difficulty eating/swallowing, diarrhea (if GI mucosa affected).
• Duration: Usually resolves in 2–3 weeks.
• Grading: WHO or CTCAE (Grade 1 = erythema, Grade 4 = alimentation impossible).

Complications

• Severe pain → ↓ oral intake, malnutrition.
• Dose-limiting toxicity → may require chemo dose reduction/delay.
• Secondary infection risk (oral candidiasis, bacteremia in neutropenia).

Management & Prevention

🔹 Preventive Strategies

• Oral care protocols: Gentle brushing, saline/bicarbonate rinses.
• Cryotherapy: Ice chips during 5-FU bolus or melphalan infusion.
• Palifermin (Kepivance®): Recombinant keratinocyte growth factor; used in HSCT conditioning with TBI + high-dose chemo.
• Low-level laser therapy (LLLT): May reduce severity (esp. in HSCT).

🔹 Treatment

• Supportive:
  • Topical anesthetics (lidocaine rinses, “magic mouthwash”).
  • Coating agents (sucralfate).
  • Systemic analgesics (opioids for severe pain).
  • Antifungal/antiviral/antibacterial prophylaxis if neutropenic + ulcerated.
• Nutrition support: Enteral/parenteral feeding if severe.

Pharmacist Pearls

• Always anticipate mucositis risk with MTX, 5-FU, melphalan.
• Encourage meticulous oral care starting before chemo.
• Recommend cryotherapy during short half-life agents (e.g., 5-FU bolus, melphalan).
• For HD-MTX, mucositis is an early sign of delayed clearance/toxicity → check MTX levels, renal function, leucovorin rescue adequacy.
• Severe mucositis = infection portal → watch for febrile neutropenia.