Mixed angioinvasive exserohilum and scedosporium infection in a patient with AML
Authors: Preetesh Jain, Priyadharsini Nagarajan, Parikshit Prayag, Christopher B. Benton, Tapan Kadia, Roman Groisberg, Dimitrios P. Kontoyiannis, Victor E. Mulanovich, Naveen Pemmaraju
Journal: American Journal of Hematology (2016)

A 65-year-old man, an avid duck hunter presented for management of newly diagnosed AML (acute myeloid leukemia). One week before, he developed pruritus and erythema on his left leg after recently walking through tall grass in Louisiana wetlands. He developed a "black spot" and ulcer in the center of the worsening erythematous area. Physical examination by a local physician revealed a painful erythematous ulcerated lesion over left lower extremity with central black eschar (Fig. 1A). Initial peripheral blood workup revealed 33% blasts and pancytopenia (hemoglobin-4.3 g/dL, WBC-1.17 K/μL, platelets-50 K/μL). After transfer to our institution and further evaluation, the AML was found to have trisomy13 and IDH1 mutation. Meanwhile, his left leg ulcer had expanded significantly and was aggressively debrided. The patient was started on broad spectrum intravenous antibiotics and voriconazole which was changed to high dose posaconazole, 10 days after presentation. During this time, he was also started on induction chemotherapy with idarubicin and cytarabine and remained afebrile throughout the first two weeks. Wound culture from leg grew Exserohilum spp. His lower extremity wound was clinically improving; however, he remained pancytopenic and developed fatigue with fever. The patient was placed in isolation due to progressive neutropenia. He then developed a new scrotal lesion 1 cm in size. A chest CT scan revealed multiple pulmonary nodules raising the suspicion of disseminated fungal infection. An echocardiogram did not detect valvular vegetations. He rapidly developed respiratory failure, atrial fibrillation and multiorgan failure with septic shock and was transferred to ICU. The patient was treated with liposomal amphotericin-B, and high dose posaconazole followed by isavuconazonium. Scrotal skin biopsy demonstrated extensive dermal and angioinvasion by septate hyphal organisms Fig. 1(B–E). Respiratory and blood cultures as well as the scrotal lesion eventually grew Scedosporium prolificans, while the rest of the infectious workup was negative. Unfortunately, he died within 4 weeks of diagnosis with active AML. A–E: Clinical and Histopathologic features of invasive fungal infection (A) Leg ulcer with black central eschar, which grew Exserohilum sp. B: Epidermal ulceration with fibrin crust (top right) with several thrombosed blood vessels (arrows) and purple fluffy material representing fungal organisms seen throughout the dermis. C: Numerous nonpigmented branching hyphae and rare conidia (arrow head). Branching at right-angles can be easily appreciated (arrows). D: Grocott's methenamine silver (GMS) stain highlights the angioinvasive fungal organisms with numerous septate (arrow heads) hyphae and several intravascular conidia (arrows). The vessel wall is indicated by the dashed line. E: Some hyphae are arranged parallel to each other, with branching at right angles, resulting in H-shaped structures (arrows). Several conidia (arrows) are also seen. Invasive fungal infection in patients with newly diagnosed AML is a major cause of death. Infection by S. prolificans and Exserohilum spp. in adults with AML is rarely described 1, 2. S. prolificans. is a rare multidrug resistant opportunistic fungus, refractory to antifungal treatments with an aggressive clinical course 3. These fungi are saprophytic and grow in soil and specifically in environments with oil contamination 4. In a large retrospective study with 8633 patients with acute leukemia, S. prolificans. was reported from only 5 patients. Lungs, soft tissues, and muscles were commonly involved 3. In vitro studies have shown that triazoles are superior to amphotericin-B against Scedosporium 5. Cases where Scedosporium infection was treatable were those where the neutrophil counts were normalized, indicating that host immunity is critical for infection control. It is possible that our patient might have acquired a mixed fungal infection through contamination of leg wound with soil from the wetlands. While Exserohilum probably caused local skin infection, Scedosporium may have penetrated via the wound and disseminated systemically after chemotherapy induced immunosuppression. This case illustrates the potential of early infection by unusual "earth" fungi by direct inoculation event early in the course of AML treatment. Clinicians treating patients with AML should be aware of rare fungal infections with potentially grave prognosis. PJ, PN, PP, and NP gathered data, evaluated the pathology and organized the figures CB, DK, VM, and NP managed the patient. All Authors have reviewed and approved the manuscript and do not have any disclosures.