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.