Successful desensitization of voriconazole in an immunosuppressed pediatric patient.

Voriconazole is an antifungal agent often used for empirical therapy in prolonged neutropenic fever. Type 1 hypersensitivity to voriconazole occurs in approximately 13% of the patients, which is detrimental for immunosuppressed patients susceptible to invasive fungal infections. Successful desensitization to voriconazole has been reported in 1 adult; however, there are no desensitization protocols published for pediatric patients. We successfully desensitized an immunosuppressed pediatric patient in the intensive care unit to voriconazole. A 13-year-old boy with a diagnosis of preeB-cell acute lymphoblastic leukemia was admitted to the pediatric intensive care unit for neutropenic fever, diarrhea, and diffuse abdominal pain. Two weeks before admission, the patient was treated for herpes simplex virus stomatitis with acyclovir. The patient had received a course of consolidation chemotherapy 4 weeks previously. Initial physical examination was remarkable for stomatitis and perirectal erythema. His abdomen was negative for tenderness, distention, or peritoneal signs. The patient was febrile to 101 F, with a heart rate of 95, blood pressure of 115/78 mm Hg, respiratory rate of 20, and O2 saturation of 98% on room air. Laboratory values showed neutropenia, with absolute neutrophil count of 146; anemia, with hemoglobin level of 6.6; thrombocytopenia, with 3000 platelets; transaminitis, with aspartate aminotransferase 102 and alanine transaminase 62; and positive C difficile toxin. Abdominal computed tomography revealed significant wall thickening of ascending colon and cecum, concerning for neutropenic colitis. The patient was initially given vancomycin, flagyl, meropenem, cefepime, and oseltamivir for presumptive influenza while awaiting antigen confirmation. Prophylactic trimethoprim-sulfamethoxazole and acyclovir were continued. Seven days after initial admission, the patient remained febrile to 102 F. Blood, urine, and fungal cultures remained negative. Empiric antifungal coverage against Candida was started, and 100 mg of micafungin was infused over 1 hour. This was the patient’s first exposure to micafungin. Approximately 40 minutes later, the patient developed acute wheezing, facial swelling, and pruritic urticarial rash over his chest, back, and abdomen. His heart rate increased to 160 and blood pressure dropped to 106/45 mm Hg. The patient was given 0.3 mL of epinephrine (1:1000) intramuscularly, 5 mg of albuterol via nebulization, 50 mg of diphenhydramine intravenously, 60mg of solumedrol intravenously, 150 mg of ranitidine intravenously, and 2 L of normal saline intravenous bolus. His respiratory distress and tachycardia improved. Facial swelling and urticarial rash resolved over the next few hours. Twenty-eight hours later, voriconazole was initiated given that it was a different class of antifungal agent. The patient had never been exposed to voriconazole previously. Voriconazole was administered in the form of a graded challenge, beginning with 1/200th of the total dose. At 1 mg, the patient developed another anaphylactic reaction with facial urticaria and wheezing. Voriconazole was promptly discontinued, and intravenous solumedrol and nebulized albuterol were given with resolution of symptoms. Skin prick testing to voriconazole was performed, with a 5-mm wheal and a 10-mm flare elicited at 1/10 dilution of intravenous concentration (5 mg/mL) (Figure 1). Test results in 2 controls were negative at this dilution. Intravenous voriconazole was restarted after a desensitization regimen (Table I). Given the patient’s anaphylaxis