Subcutaneous inflammatory edema induced by MINE chemotherapy

BACKGROUND: The MINE regimen (mitoguazone, ifosfamide, vinorelbine and etoposide) is a salvage chemotherapy for relapsed and refractory Hodgkin's disease. CASE REPORTS: We report the cases of a 16-year-old girl and a 17-year-old boy who had Hodgkin's disease and developed painful and massive subcutaneous inflammatory edema after MINE chemotherapy. Morphine was unable to control pain leading to major functional disability of joint movement. One patient had an elevated creatine kinase level, hypoalbuminemia, hypodermic and muscular edema at magnetic resonance imaging and diffuse hemorrhagic hypodermic edema at skin biopsy. The other patient was found to have only hypoalbuminemia. The clinical course was favorable in both cases within a few weeks, but with recurrent episodes of pain and localized areas of fat necrosis five months later in one case. DISCUSSION: This side effect of MINE chemotherapy - subcutaneous inflammatory edema, myalgia and skin pain - has not been described previously for the different components of the regimen. Three clinicopathological hypotheses could be put forward: capillary leak syndrome, panniculitis, toxic fasciitis. The causal drug remains undetermined, but the most likely would be vinorelbine because of the chronology of the eruptions during the first and last days of chemotherapy and because of the known vascular toxicity of vinorelbine which could explain a capillary leak syndrome.