RESULTS
A 6-year-old male was receiving intensive chemotherapy for the treatment
of refractory acute lymphoblastic leukemia with a regimen consisting of
oral 6-mercaptopurine, an intravenous continuous infusion of
methotrexate; leucovorin; and an intrathecal combination of
methotrexate, cytosine arabinoside, and dexamethasone. On day seven
after starting this regimen, the child developed diffuse painful oral
sores. Pain was worse when chewing and swallowing, and he gradually
stopped eating solids and was barely able to swallow sips of liquids.
His pain was initially managed with an oral hygiene protocol including
an oral rinse and swab with alcohol-free 0.2% chlorhexidine four times
a day. He was given ice chips and scattered doses of a morphine elixir
without meaningful relief. As his clinical condition rapidly
deteriorated, he was occasionally lethargic with persistent drooling; at
this point, he had a total weight loss of 450 grams.
His physical examination revealed an irritable child with a weak and
uncomfortable appearance. He had a blood pressure of 88/54 mmHg, pulse
of 148 beats/min, respiratory rate of 24 breaths/min, and a tympanic
temperature of 37.3 °Celsius.
He avoided examination of his oral cavity, but a limited view revealed
thick saliva, scalloping (i.e. imprints of the teeth on the tongue),
coating of the mucosa of
sublingual area and the soft palate and scattered compromised oral
mucosa of the cheeks. There was evidence of painful erythematosus
plaques with localized spots of mucosa ulceration (Figure 1). The
patient’s mucositis was considered grade four on the
World-Health-Organization classification and grade six on the Children’s
International-Mucositis Evaluation-Scale. The remainder of the physical
findings were consistent with dehydration. Blood tests showed a white
cell count of 8,800 cells/mL, hemoglobin of 9.7 g/dL, and hematocrit of
29.3%. Urine analysis revealed specific gravity of 1.035, his lactic
acid level was 2.8 mmol/L. The remainder of the blood test, chemistry,
and hepatic function panels were normal.
A trial of methylene blue 0.05% diluted in normal saline solution was
provided. The child was instructed to take sips of 3-5 mL of this
mixture, hold it in his mouth for 5 minutes, and then spit out the
mixture. This mixture was judiciously provided every 4 hours. As the
child became more comfortable with the protocol, he was able to hold the
methylene blue mixture in his mouth for 5 minutes before spitting it
out. After the first dose, drooling was no longer evident. After the
second dose, he was eager and able to drink fluids, subsequently he no
longer received morphine after three doses. The patient rapidly
progressed from being able to eat a soft to a solid diet and was
discharged home on day seven after admission. The only adverse effect
observed was transient blue discoloration of his mouth and asymptomatic
faint greenish discoloration of his feces and urine, likely from
unintentional swallowing of the treatment mixture.