Case Presentation: A 73-year-old Caucasian male presented with worsening fatigue and dyspnea for several days. His comorbidities included remote history of essential thrombocytosis controlled with aspirin, hypertension, chronic kidney disease, and mitral valve repair. He was admitted to the medical ICU for acute hypoxic respiratory failure requiring mechanical ventilation. His physical exam was remarkable for respiratory distress and diffuse rhonchi bilaterally. On laboratory evaluation, patient had severe leukocytosis, anemia, and thrombocytopenia. Chemistries revealed acute renal failure, hyperuricemia and hyperphosphatemia. ABG noted compensated metabolic acidosis.With profound leukocytosis, hyperuricemia, and hyperphosphatemia in the setting of an acute kidney injury, there was concern for TLS requiring initiation of rasburicase therapy. However, several hours following this intervention, patient developed peripheral cyanosis with worsening hypoxia. Repeat ABG revealed methemoglobin level of 12.3 and PaO2 level of 285 consistent with methemoglobinemia. Patient was also noted to have hemolytic anemia requiring blood transfusions. He received multiple doses of intravenous methylene blue with subsequent resolution of methemoglobinemia. Patient was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency, levels of which were normal.
Discussion: This case describes a 73-year-old male who developed methemoglobinemia following administration of rasburicase. Rasburicase, a recombinant form of urate oxidase enzyme, breaks down uric acid to allantoin, liberating hydrogen peroxide, a free radical, as a byproduct. With these free radicals, the oxidative stress can cause methemoglobinemia. Clinical presentation is variable and can include mild cyanosis, dyspnea, hypoxia, seizures, coma and/or death. They can also develop hemolysis concurrently. Typically, treatment is indicated at methemoglobin levels greater than 20% and to those who are symptomatic. It primarily includes discontinuation of the offending agent likely permanently, this being rasburicase in our patient, along with supportive care and administration of methylene blue. Especially in G6PD patients, intravenous methylene blue itself can cause or worsen hemolysis. Furthermore, timely blood transfusions and supplemental oxygen may prevent the need for methylene blue. While reports of rasburicase induced methemoglobinemia are noted in G6PD deficiency patients, it is rare for this to occur in non-G6PD deficiency.
Conclusions: This case report portrays one of the rare side effects of rasburicase, methemoglobinemia. It also shows the difficulties in treating patients with methemoglobinemia since treatment with IV methylene blue can precipitate hemolysis. In summary, this case highlights the importance of having a high suspicion for diagnosis of methemoglobinemia as an etiology in patients who develop acute hypoxia and receive rasburicase; there should be cautious administration of intravenous methylene blue.