3. Discussion
Oral mucositis (OM) is a common adverse event in patients receiving
chemotherapy. Its clinical manifestation ranges from mild erythema and
soreness to extreme pain and ulceration, significantly affecting
patient’s quality of life3. Specific drug therapy has
been associated with an increased risk of developing mucositis;
etoposide is excreted in the saliva which increases its oral
toxicity1. In rare cases, severe OM can result in
significant edema of the upper airway leading to airway
obstruction4.
Pediatric patients are more prone to develop OM with increased
severity5. Its prevalence is reported to exceed 90%
among children under 12 years old receiving chemotherapy for
hematological malignancies compared with 40% in the adult
counterparts1. This has been attributed to the greater
number of mitoses in the basal epithelium in younger patients, making
the epithelial cells more vulnerable to cytotoxic
effects6. The duration of OM in the pediatric
population tends to be shorter reflecting their greater healing
capacity6.
Pediatric patients with severe OM are at greater risk of airway
compromise due to their narrower airway6. The exact
prevalence of upper airway complications in the pediatric patients
following chemotherapy is unknown. One study reported that 10.5% of the
pediatric patients following bone marrow transplantation required
mechanical ventilation, of which upper airway obstruction due to
mucositis accounted for 13%7.
Typically, OM develops 10-14 days after initiation of chemotherapy and
heals within 2-4 weeks, consistent with the clinical course of
neutropenia8. Neutropenia has been reported to play a
key role in the development of OM. Severity of OM is associated with the
degree of neutropenia, and resolution coincides with granulocyte
recovery8. This is assumed to be a result of
neutropenia leading to impaired mucosal defence and
repair8.
Management of OM is crucial as it provides a portal for potentially
life-threatening infection8. Previous studies have
shown that the risk of infection increases with increasing grade of
OM8. As most patients with OM develop neutropenic
fever, broad spectrum beta-lactam with combination of antifungal and
antiviral agents is commonly used as a standard treatment to cover
gram-negative bacteria, Coagulase-negative Streptococci ,Streptococcus viridans , Candida albicans and Herpes
simplex 6, 9, 10. However, fever remains unexplained
in 30-50% of neutropenic patients with no evidence of
infection11. Furthermore, fever persists for 4-5 days
or even longer in approximately 30% of cases despite adequate microbial
treatment directed at bacteria and fungi11. In these
cases, fever may not be necessarily related to infection and may be a
manifestation of the inflammatory process contributed by the mucositis
itself9, 11. In a report examining patients receiving
chemotherapy for treatment of acute leukemia, inflammation was shown to
be correlated with the occurrence of mucositis. The inflammatory
response is elicited by formation of reactive oxygen species due to DNA
damage of the epithelial cells, followed by amplification of
proinflammatory and inflammatory cytokine release triggered by various
microbial motifs (Pathogen-associated molecular patterns) released from
invading microorganisms and damaged tissues (Damage-associated molecular
patterns) through the distorted mucosal barrier, manifesting systemic
fever and further tissue damage11.
In the current case, the patient remained febrile despite treatment with
broad spectrum antibiotics, antifungal and antiviral agents lacking
evidence of infection. Regarding her prompt defervescence coinciding
with recovery of mucositis, her fever may have been a manifestation of
the inflammation of mucositis, irrelevant of infection. Currently no
guideline is provided regarding the use of G-CSF on mucositis due to
insufficient evidence12. Yet, the possibility of
infection could not be discarded in this circumstance and treatment with
broad-spectrum antimicrobials combined with G-CSF was continued.
In the current case, the patient was successfully extubated following
recovery of mucositis but required prolonged mechanical ventilation.
Determination whether to perform tracheostomy in this case was difficult
considering its completely reversible pathology.
Airway management with intubation possesses a significant risk of
complete airway obstruction and death in case of accidental extubation,
mandating deep sedation (paralysis may be considered) and prolonged
mechanical ventilation which significantly delays patient recovery.
Placement of a tracheostomy provides a secure airway and enables safe
management of the patient with further advantages of improved patient
comfort, reduced sedative requirements and early patient recovery.
Although surgical tracheostomy in the presence of severe
immunosuppression and thrombocytopenia is not a contraindication, it may
be associated with increased risk of surgical complications. Studies
regarding this topic are scarce, especially in the pediatric population
and do not support a recommendation13-15.
Thus, airway management in these patients must be determined prudently
regarding the expected duration of neutropenia, weighting the risks and
benefits on an individual case basis.