Bone Marrow Transplantation (2000) 26, 645–648 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt The spectrum of Malassezia infections in the bone marrow transplant population VA Morrison1,2 and DJ Weisdorf1 1Bone Marrow Transplant Unit, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA Summary: Malassezia consists of seven species, most human infec- tions are caused by Malassezia furfur, which includes the A consecutive series of 3044 patients who underwent species previously known as Pityrosporum ovale and BMT at the University of Minnesota over a 25 year per- Pityrosporum orbicularae.6–9 Sporadic cases of fungemia, iod were reviewed for the post-transplant occurrence of meningitis, urinary tract infection, and cutaneous infection infection caused by the yeast Malassezia furfur. Six caused by Malassezia pachydermatis have been patients, ranging in age from 1 to 54 years, developed reported.10,11 Malassezia sympodialis is an unusual cause Malassezia infections at a median of 59 days post trans- of human infection.12 These dimorphic saprophytic yeast plant. Five patients were allogeneic transplant recipi- isolates are known to have unusual lipophilic growth ents; the remaining patient had undergone autologous requirements, in that growth occurs on standard fungal transplantation. A spectrum of clinical manifestations media such as Sabouraud dextrose agar only when the cul- of Malassezia infection was seen in these patients, ture medium is supplemented with a source of including infections of mucosal surfaces and the skin, in medium/long-chain fatty acids. Although a variety of Mal- addition to catheter-related fungemia. Unlike many of asssezia infections have been reported in nonimmuno- the other more common opportunistic fungal infections compromised patients, this fungus may also complicate the in immunocompromised patients, neutropenia and the course of BMT patients, with a spectrum of manifestations use of broad-spectrum antimicrobials do not appear to in this population. We report six BMT patients who be significant risk factors for Malassezia infections in developed Malassezia infection during the post-transplant the BMT population. In addition, disseminated fungal period, describe the clinical spectrum of infection, and infection despite the presence of fungemia is uncommon. discuss approaches to therapy. Lastly, the outcome of Malassezia infections in these patients, whether folliculitis, mucosal infection, or fung- emia, appears to be quite favorable, in contrast to the Patients and methods poorer outcome with many other fungal infections in A consecutive series of 3044 patients who underwent bone BMT patients. Catheter removal and discontinuation of marrow (autologous, allogeneic, syngeneic) or stem cell intravenous lipids are important for a successful out- transplantation at the University of Minnesota from 1974 to come in fungemic cases. Bone Marrow Transplantation April 1999 was reviewed for the occurrence of Malassezia (2000) 26, 645–648. infections in the post-transplant period. Of the transplants, Keywords: bone marrow transplantation; Malassezia; 1942 were allogeneic, and 1102 were autologous. Patients infection were identified in chronological fashion by a unique patient number (UPN). Clinical data was obtained from review of prospectively collected information in the University of Fungal infections are a major cause of morbidity and mor- Minnesota Bone Marrow Transplant Data Base along with tality in immunocompromised cancer patients, especially medical records, microbiology/surgical pathology reports, those who undergo BMT.1–5 Although most fungal infec- and autopsy summaries. The post-transplant period was tions in the transplant population are caused by Candida defined as the interval from transplant (day 0) to the date and Aspergillus species, over the past decade there has been of last follow-up or death. Infections were documented by increasing recognition of other opportunistic fungi with a histopathologic evidence of tissue invasion and/or culture characteristic clinical spectrum of infection in these pro- isolation of the causative agent either from a sterile body foundly immunosuppressed patients. Although the genus fluid or biopsy material. The WBC at the time of infection was noted, as was the presence and grade of acute/chronic GVHD. Treatment data and clinical outcome were reviewed. Correspondence: Dr VA Morrison, Sections of Hematology/Oncology and Infectious Disease, 111E, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA Microbiology 2Present address: Sections of Hematology/Oncology and Infectious Dis- ease, Veterans Affairs Medical Center, Minneapolis, MN, USA Blood for fungal blood culture was inoculated into tubes Received 1 October 1999; accepted 6 June 2000 of the BACTEC system (Becton Dickinson, Cockeysville, Spectrum of Malassezia infections in the BMT population VA Morrison and DJ Weisdorf 646 MD, USA) to 1983, and subsequently, the Dupont Isolator pathologic changes consistent with Pityrosporum follicu- System (Wampole Laboratories, Cranbury, NJ, USA) was litis. The patient with vulvar infection (UPN 1423) utilized. Fungi isolated were then inoculated on to an presented with a vulvar discharge, low-grade fever, and inhibitory mold agar slant and a brain–heart infusion agar non-erythematous vulvar mucosa at day 58 post transplant. slant containing blood and antibiotics for fungal Malassezia furfur grew from a vulvar swab culture. This species/genus identification. Biopsy specimens submitted patient’s hyperalimentation had been discontinued 1 day for fungal culture were inoculated on to four types of agar prior to infection diagnosis. Both patients with Malassezia media and incubated at 37°C: sheep blood agar, inhibitory furfur fungemia presented late in the post-tranplant course mold agar, brain–heart infusion agar with blood and anti- (days 94, 114), and had neutrophil engraftment for 2 to 3 biotics, and mycobiotic agar (containing chloramphenicol months prior to infection. One (UPN 1101) was on hyperal- and cyclohexamide to inhibit saprophytic fungi). Malasse- imentation including intravenous intralipids, and developed zia was identified by characteristic microscopic morpho- intermittent low-grade fevers of unclear etiology. Malasse- logic findings in addition to specific fungal culture growth zia was isolated from six of nine blood cultures drawn over requirements. The thick-walled, 3–8 µm in diameter yeast 5 consecutive days. Examination of a peripheral blood is round to oval, with a broad-based bud and collarette at smear for 2 days prior to initial culture isolation revealed one pole. Hyphae and pseudohyphae are usually absent in the presence of budding yeast, as did a peripheral blood culture; however, in clinical specimens short, slightly smear 4 days later. The second fungemic patient (UPN curved septate hyphae may be seen. The yeast grows in 1301) also presented with fever, which was thought to be culture in 2 to 4 days, with optimal growth at 35–37°C, related to Gram-negative sepsis diagnosed 1 day earlier. but only when the culture medium is supplemented with Blood cultures the following day grew Malassezia furfur. sterile olive oil, lanolin, or Tween 80, as a source of fatty In both of these fungemic patients, physical examination acids. If Malassezia is suspected based upon the typical was unremarkable; specifically, no rash or hepatosplenome- yeast appearance from initial blood culture isolation, the galy, was present. media of all subsequent cultures (subculture from the posi- tive blood culture bottle for fungal isolation/identification, Risk factors, therapy and outcome catheter tip cultures, etc) are supplemented with a fatty acid source. Typical colonies are smooth, glistening, and cream- All six patients had central venous access devices (CVAD) colored. The yeast will assimilate dextrose, but not other in place. Two patients (UPN 1101, 1423) had been receiv- sugars. It is nonfermentative and urease positive. ing hyperalimentation immediately prior to or at the time of fungal infection diagnosis. In all cases, there was no evidence of local infection at the catheter site. At time of Histology infection diagnosis, all patients were on antifungal prophy- Tissue biopsies were stained with hematoxylin and eosin laxis (either clotrimazole troches or nystatin swish and in standard fashion. When fungal infection was suspected, swallow). In the patients with Malassezia fungemia, the additional sections were stained with Gomori-methena- CVAD was removed, one at the time the positive blood mine-silver and periodic acid-Schiff stains to highlight culture was identified, and the other after several days of fungal elements. intermittent fungemia. Culture of the catheter tip was nega- tive for fungal growth in both cases. Subsequent fungal blood cultures drawn after CVAD removal were negative. Results No patients received systemic antifungal therapy. The patient with scrotal involvement was treated successfully Clinical presentation with topical nystatin powder. Topical ketoconazole resulted in resolution of infection in the other cases of cutaneous Over the 25-year period from 1974 to April 1999, 3044 infection. The vulvar discharge in the remaining patient was patients underwent BMT at the University of Minnesota. self-limited, resolving without antifungal therapy. Six of these patients (0.002%) developed Malassezia infec- tions at a median of