The pathological process of oral mucositis starts in the
cell (DNA, the cell wall, etc.) when chemotherapy and/or radiation
is started.11
- The pathogenesis of mucositis is not entirely understood, but
involves direct and indirect mechanisms. The direct effects, caused
by irradiation and chemotherapy, cause lesions of the oral
epithelium by interfering with cell renewal and by causing
apoptosis. The indirect effects lead to oral mucositis through the
release of inflammatory mediators, the loss of protective salivary
components and neutropenia induced by the treatment. These factors
increase the likelihood of the emergence of bacterial, viral and
fungal infections on the damaged mucosa.5
Stage 1: Initialization
This stage corresponds to the lesions directly caused by the
irradiation or the chemotherapy which adversely affects the cells
and the strands of DNA in the basal epithelium and the submucosa.
Free radicals (Reactive Oxygen Species or ROS) are also generated
and play a mediating role in the biological events of the later
stages (direct damage to the mucosa and indirect damage by
activating transcription factors).
Stage 2: Primary response to the adverse effect on the
cells and the DNA
The adverse effect on the cells and the DNA, and also the ROS,
activates a cascade of reactions which bring about the production
of pro-inflammatory cytokines. These compounds stimulate a number
of pathways leading to lesions or the death of basal cells by
apoptosis.
Stage 3: Amplification of the signal
The release of pro-inflammatory cytokines not only damages the
cells, but also provides a positive feed-back which amplifies the
lesions caused directly by the radiation or the chemotherapy.
During this stage the tissue appears to be relatively healthy, with
only minor erythemas.
Stage 4: Ulceration
This stage is characterized by painful lesions, subject to
colonization by bacteria. This bacterial proliferation will cause
new tissue damage and activate the production and release of
additional pro-inflammatory cytokines by the infiltrating
mononuclear cells.
Stage 5: Healing
Mucositis is generally an acute event that disappears gradually
after the cancer treatment has stopped.
After the scarring stage the mucosa appears normal, but residual
neo-vascularization persists. It is therefore more fragile and
vulnerable to cytotoxic attack and is therefore at a higher risk of
severe mucositis in the event of future courses of chemotherapy
and/or radiation theraphy.13