In patients with acute myelogenous leukemia, posaconazole prophylaxis has been shown to prevent deep invasive fungal infections, including mucormycosis. In the present case, posaconazole prophylaxis was initiated in a 58-year-old man undergoing induction chemotherapy for acute myelogenous leukemia. Three weeks after initiating chemotherapy, he developed a tender violaceous macule on the shaft of his penis. The initial differential included fixed drug eruption versus pyoderma gangrenosum. However, punch biopsy ultimately showed mucormycosis, and cultures grew Rhizopus species, despite therapeutic posaconazole trough. He was treated with intravenous amphotericin B and required right orchiectomy, penectomy, and hyperbaric oxygen therapy. Oral posaconazole was reinstituted after completion of amphotericin B course, and at 4 months follow-up, his penectomy site was fully healed. As demonstrated by the present case, not all mucormycoses are prevented by posaconazole prophylaxis. A high index of suspicion and early biopsy for prompt diagnosis are of critical importance in improving outcomes.

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Rationale and objectivesThe role of human lung megakaryocytes in homeostasis and their dynamics in disease states remain unknown. We sought to investigate whether megakaryocyte/platelet gene signatures are altered in IPF.MethodsWe analyzed publicly available transcriptome datasets of lung tissue, bronchoalveolar lavage (BAL) cells, and peripheral whole blood from IPF patients and healthy controls. Enrichment of megakaryocyte and platelet gene signatures in those datasets were estimated using xCell, a novel computational method. Furthermore, we analyzed whether mean platelet volume (MPV) and platelet counts in peripheral blood are associated with lung transplant-free survival in our IPF cohort.ResultsIn lung tissue, megakaryocyte scores were significantly lower in IPF than in controls. In BAL cells, platelet scores were significantly lower in IPF than in controls, and lower platelet scores were associated with lower lung transplant-free survival in IPF. In contrast, in blood, megakaryocyte scores were significantly higher in IPF than in controls, and higher megakaryocyte scores were associated with lower disease progression-free survival in IPF. Furthermore, higher MPV was associated with lower transplant-free survival in our IPF cohort, independent of age, sex, forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO).ConclusionsIn IPF, megakaryocyte/platelet gene signatures were altered in a compartment-specific manner. Moreover, those signatures and MPV in blood were associated with important clinical outcomes such as transplant-free survival. These findings provide new insights into altered megakaryocyte/platelet biogenesis in IPF and suggest the potential utility of megakaryocyte/platelet-based biomarkers in IPF.

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