Denileukin diftitox (ONTAK) is a recombinant cytokine-targeted fusion protein that delivers the catalytic domain of diphtheria toxin to lymphoma cells expressing the interleukin-2 receptor (IL-2R).Vascular leak syndrome(VLS) is a complication of ONTAK therapy and is usually a self-limited illness1.The following is the first case report of severe VLS presenting as ARDS.
A 53-year-old healthy male with mycosis fungoides received 5 daily infusions of ONTAK. Two days later he developed intractable nausea, fever(41°C) and dyspnea progressing over 48 hours to acute respiratory failure requiring intubation. His PaO2/FiO2 ratio of 50, pulmonary capillary wedge pressure of 15 mmHg and chest-x-ray were consistent with a picture of ARDS. His cardiac index was 4.4L/M2, serum albumin 2.6gms/dL, white blood cell count 44000 and all cultures were negative with no source of infection identified. His mean arterial pressure dropped to 40mmHg and he received intravenous crystalloids, antibiotics, vasopressors, recombinant drotrecogin alfa and mechanical ventilation. Within 48 hours his hypoxemia and shock resolved completely leading to extubation despite a positive fluid balance of almost 10 litres.DISCUSSION: Upto 27% of patients receiving denileukin diftitox can develop VLS,usually a self-limited illness defined as the occurence of at least 2 of the following: edema, hypoalbuminemia(< 2.8gms/dL) and/or hypotension occuring during days 1-14 of the treatment 1. The low wedge pressure, normal cardiac index and recovery despite non-response to diuretics and positive fluid balance makes congestive heart failure an unlikely cause of this patient’s respiratory failure.Although fulfilling conventional criteria for ARDS2 given the rapidity of recovery it is more likely that severe VLS was the underlying pathophysiology.
In patients receiving denileukin diftitox(ONTAK), vascular leak syndrome(VLS) should be considered in the differential diagnosis of ARDS.
V. Pai, None.