The 5-phases of Oral Mucositis Adapted from Sonis:
- Phase I—Initiation Chemotherapy or radiation-induced reactive oxygen species (ROS) and lipid peroxidation results in DNA damage, release of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern molecules (DAMPs) and cellular apoptosis.
- Phase II—Signaling ROS stimulate the NF-kB pathway, which induces production of proinflammatory cytokines (TNF-α, IL-1β, IL-6).
- Phase III – Amplification Proinflammatory cytokines trigger tissue injury, apoptosis, vascular permeability, and activation of cyclooxygenase-2.
- Phase IV—Ulceration Ulceration occurs, which serves as a portal of entry for microorganisms. The presence of bacteria activate macrophages and neutrophils to further produce proinflammatory cytokines.
- Phase V—Healing Signaling from the submucosa promotes epithelial migration, proliferation and differentiation.
Table I Classification of Oral Mucositis according to the World Health Organization (WHO).
- No subjective or objective evidence of mucositis.
- Oral pain with or without erythema, without ulceration.
- Erythema and ulceration, can swallow solids.
- Erythema and ulceration, unable to swallow solids.
- Erythema and ulceration, unable to feed.