A 59-year-old white male with a history of mantle cell lymphoma underwent hematopoietic stem cell transplantation from a matched unrelated donor in 2004. His lymphoma relapsed in July 2005, and the patient received chemotherapy and a donor lymphocyte infusion. In September 2005, he developed skin and rectosigmoid graft-versus-host disease and was started on mycophenolate mofetil, tacrolimus, and prednisone. The patient was taking trimethoprim/sulfamethoxazole, acyclovir, and voriconazole for prophylaxis. In December 2006, while hospitalized with active gastrointestinal graft-versus-host disease, he developed the acute onset of multiple, nontender, maculopapular, purple-to-black skin lesions. The lesions initially involved the patient's face and scalp but within 1 to 2 days spread to his torso and extremities, including his palms and soles (Fig. 1). There was no fever, but the patient developed mild shortness of breath, and a computed tomography of the chest revealed innumerable lung nodules. A bronchoscopy and skin biopsy were performed. The skin biopsy Gomori methenamine-silver (GMS) and periodic acid-Schiff (PAS) stains are shown on Figure 2.
What is your diagnosis?
Diagnosis: Disseminated infection with Exserohilum rostratum.
The skin biopsy revealed fungal hyphae with branching forms on Gomori methenamine-silver and periodic acid-Schiff stains, which were surrounded by foci of acute inflammation (Fig. 2). The fungal culture became positive for E. rostratum 6 days later (Fig. 3). A sputum culture was also positive for E. rostratum. Based on the patient's clinical manifestation, microbiologic findings and histopathologic features, a diagnosis of disseminated E. rostratum infection was made.
Exserohilum rostratum is the most commonly isolated species of Exserohilum, a dematiaceous filamentous fungus that lives in the soil and on plants; other species include Exserohilum longirostratum and Exserohilum mcginisii. Exserohilum rostratum grows rapidly in culture and is characterized by dark septate hyphae and brown, straight to slightly curved conidia. It may be differentiated from other dematiaceous molds, including Bipolaris spp, Drechslera spp, and Helminthosporium spp, by its characteristic longer conidiophores, the number of septa (5-12), and the strongly protruding hilum of each conidium.1
Exserohilum rostratum has been implicated in cases of keratitis, 2-4 cutaneous disease, 5-10 and sinusitis. 11-13 Most of the cases of E. rostratum have been reported in severely immunocompromised hosts. Notably, 1 patient with a plastic anemia died after he developed sinusitis and invasive pulmonary disease with this organism.14 Among the limited number of cases of invasive diseases with E. rostratum reported, the outcome has depended on the appropriate therapeutic intervention and the immune status of the host. Although interpretive criteria for E. rostratum susceptibility testing have not been established, minimal inhibitory concentrations for major antifungal agents should be obtained. Combination treatment (ie, a polyene with an azole) has been suggested by other investigators who have treated diseases caused by E. rostratum. 11 In cases of invasive sinusitis, surgical debridement is strongly recommended. As with other opportunistic infections in immunocompromised hosts, reconstitution of the patient's immune status is imperative for resolution of the infection.13 Persistent neutropenia and use of immunosuppressive agents have historically been associated with poor outcomes.7,11,15 In the case presented, the minimal inhibitory concentrations for E. rostratum at 48 hours were 0.5 μg/mL for amphotericin B, 0.5 μg/mL for caspofungin, 0.03 μg/mL for itraconazole, 0.06 μg/mL for voriconazole, and less than 0.015 mg/mL for posaconazole. The patient was started on liposomal amphotericin B (10 mg/kg per day) and intravenous itraconazole (200 mg/d). In addition, his immunosuppression was slowly tapered. His skin lesions shrank within days and eventually disappeared. The lung lesions stabilized. However, the patient succumbed to complications from his underlying disease 1 month later.
The authors thank Donald Jungkind, PhD, and Mindy Tokarczyk, from the Department of Microbiology, Thomas Jefferson University Hospital, for their significant help.
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