Description

• A condition affecting any part of the alimentary tract (most commonly the oral cavity), associated with chemotherapy
• Mucositis ranges from erythema to erosion to ulceration, causing pain (oral cavity) and diarrhea (GI tract).
• Mucositis causes significant pain sometimes treatable with local therapies but often requiring parenteral opioids.
• A leading cause of delay or reduction in chemo or radiation therapy
• Mucositis limits oral intake, decreases quality of life, raises the probability of affective disorders, and increases the risk for systemic infection.

Epidemiology

Incidence
Mucositis can affect up to 100% of patients undergoing high-dose chemotherapy prior to hematopoietic/stem cell transplantation, up to 85% of patients receiving radiation therapy for head/neck cancers, and up to 40% of patients undergoing chemotherapy alone.

Prevalence

• The type(s) and dose of chemotherapeutic agents and underlying genetic factors determine the frequency and severity of mucositis.
• Many chemotherapeutic agents cause mucositis. Cytotoxic agents such as 5-fluorouracil, capecitabine, and cisplatin are most common.
• Other agents include, but are not limited to, methotrexate and related antimetabolites, doxorubicin, receptor tyrosine kinase inhibitors (sunitinib, sorafenib), epidermal growth factor receptor (EGFR) inhibitors (cetuximab, erlotinib), and mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus).
• Head/neck and total body irradiation also increase risk for developing mucositis.

Etiology and Pathophysiology

Mucositis progresses through five stages.

• Initiation: direct cellular damage from radiation and/or chemotherapy leading to epithelial cell destruction and free radical creation
• Upregulation: Free radicals activate second messengers to upregulate proinflammatory cytokines.
• Amplification: Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) produce further damage to mucosal cells and activate immune cellular response.
• Inflammation/ulceration: Inflammatory cell infiltrates cause mucosal ulceration and are further stimulated by colonizing flora.
• Healing: Inflammation diminishes to allow epithelial hypertrophy and restoration of the mucosal barrier (1).

Genetics
Genetic polymorphisms have been identified that may predispose individuals to methotrexate-induced mucositis; other genetic factors under investigation

Risk Factors

• Type, dose, and duration of chemotherapeutic agent
• Frequency, dosing, and location of radiation therapy
• Genetic predispositions are not fully understood.

General Prevention

• Pretreatment oral assessment 2 to 3 weeks prior to initiation of therapy to address asymptomatic oral infections, dental caries, and periodontal disease (1,2)
• Use of oral care protocols including frequent use of nonmedicated oral rinses, flossing, and brushing with soft toothbrushes (1,3)[B]
• Aggressive treatment of xerostomia with saliva replacements or sialogogues to promote healthy oral mucosa (2)
• Prevention of GI mucositis includes basic bowel care, adequate hydration, and avoiding transient lactase deficiency.
• There is currently no localized therapeutic intervention that is clinically effective for the prophylaxis of chemotherapy-related alimentary mucositis (4)[C].

Commonly Associated Conditions

Superinfections with fungi, bacteria, or viruses. See “Complications.”