Clinical Pearls & Morning Reports
Published March 8, 2023
Mucormycosis is a rapidly progressive disease in transplant recipients. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: Describe a common feature of infection with mucorales species.
A: Mucorales species — including rhizopus, mucor, rhizomucor, cunninghamella, lichtheimia, and apophysomyces species — are highly invasive. Rhizopus, specifically, expresses proteins such as spore-coat protein homologues, which can bind to glucose-regulated protein 78 on endothelial cells and promote angioinvasion. Infection with mucorales species often results in severe necrotizing processes, including those involving the skin, which are caused by infarction of multiple capillary beds.
Q: Is the diagnosis of mucormyosis easy to make?
A: The diagnosis of infection with mucorales species is challenging because of the lack of antigen-specific tests, and it often requires growth and identification in culture or ribosomal sequencing. On histopathological examination of a biopsy specimen, the presence of pauciseptate and ribbonlike hyphae that branch at wide angles may be suggestive of mucorales species.
A: For invasive mold infection, transplantation-associated risk factors include renal replacement therapy, blood loss or transfusion of more than 40 units, reoperation, a prolonged stay in the intensive care unit, cytomegalovirus coinfection, previous mold colonization, and critical illness at the time of transplantation. Diabetes, particularly with diabetic ketoacidosis, is a commonly associated risk factor. Liver transplantation alone is associated with a risk of mucormycosis that is five times as high as the risk in the general population. Previous exposure to voriconazole can confer a predisposition to mucormycosis. The skin (e.g., the site of a chest tube, burn, trauma, or surgery) is the portal of entry in up to 56% of cases of mucormycosis, often in immunocompromised hosts. Allograft-derived mucormycosis has been reported, most often in lung-transplant recipients, and related skin lesions are common.
A: To the degree possible, a reduction in immunosuppression would be considered. The reduction or elimination of glucocorticoid therapy can improve neutrophil function and the control of diabetes. Such a reduction may result in an increased risk of graft rejection; the replacement of glucocorticoids with calcineurin inhibitors may result in an increased risk of nephrotoxicity in kidney-transplant recipients. Imaging and biopsy are performed immediately to confirm the location and extent of the disease, followed by excision of infected tissues to clean the margins. Early antifungal therapy is warranted. Prospective clinical trials investigating primary treatment for mucormycosis have focused on amphotericin B and isavuconazole. Because transplant recipients who are receiving calcineurin inhibitor therapy for immunosuppression have renal impairment, lipid formulations of amphotericin B are the preferred initial treatment for mucormycosis.