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A massive intraventricular thrombosis by disseminated mucormycosis in a patient with myelodysplastic syndrome during deferoxamine therapyNaoshi Kubota, Keisuke Miyazawa, Nahoko Shoji, Masahiko Sumi, Akihiro Nakajima, Yukihiko Kimura, Hisashi Oshiro, Yoshiro Ebihara, Kazuma Ohyashiki
First Department of Internal Medicine, Second Department of Pathology, Tokyo Medical University
Correspondence to Dr. Keisuke Miyazawa,
First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
A 70-year-old man with a 2-year history of myelodysplastic syndrome (MDS), refractory anemia, was hospitalized because of pneumonia. He had received frequent transfusions because of anemia. The total amount of blood transfusions he received during the 7 months before admission was 44 units. In the previous 6 months, he was given 500 mg of deferoxamine intravenously after every transfusion to prevent secondary hemochromatosis (total dose: 6,500 mg). On admission, a complete blood count showed a white blood cell count of 2.0x109 /L with 53% neutrophils, a hemoglobin level of 5.2 g/dL, and a platelet count of 6x107/L. The serum ferritin was 1,532 ng/ml indicating an iron overload state. Although he received a series of antibiotics and fluconazole as empiric therapy, his pneumonia progressed and pleural effusion became evident. Frequent microbiological investigations, including cultures of blood, sputum, and pleural fluids, and serum levels of endotoxin and b-D-glucan all yielded negative results. However, an intraventricular tumor mass was observed on echocardiogram on day 17 after admission, which had been undetectable 10 days earlier (Figure 1). Amphotericin B was started on the suspicion of mucormycosis. However, he soon developed coma because of multiple cerebral infarctions on day 19, and died of cerebral hemorrhage on day 21. Autopsy revealed a large intraventricular thrombosis (Figure 2). Histopathological examination of the thrombosis showed broad, irregularly-shaped, non-septal hyphae with right-angled branching, which is characteristic of mucormycosis (Figure 3). Disseminated mucormycosis was also detected in abscesses in multiple organs, including the brain, lung, liver, spleen, thyroid grand, and kidney.
Mucormycosis is an opportunistic infection caused by Mucorales zygomycetes, mostly due to the inhalation of spores. Treatment with the iron chelator deferoxamine has been reported to be one of the risk factors for developing mucormyocis in patients with iron overload (1, 2). In human plasma or on the mucosal surfaces, the amount of free iron available for microbial growth is low; almost all of the iron is bound to iron-binding proteins such as transferrin and lactoferrin or is inaccessible in tissue stores. Micro-organisms compete for the iron in the host, usually by secreting siderophores that trap iron and deliver it to the micro-organism, thus enhancing their growth. Deferoxamine B mesylate (deferoxamine) is one of the siderophores produced by Streptomyces pilosus. Therefore, administration of deferoxamine is suggested to extract iron to support the growth of the microorganism for mucormycosis and thus result in infection (3). Mucormycosis has also been reported in patients with hematological malignancies such as leukemia, lymphoma, and bone marrow transplant recipients, who were no receiving deferoxamine therapy. However, theses cases were reported to occur predominantly in the aplastic post-chemotherapy period (4). There are also some reports of mucormycosis in MDS patients not receiving deferoxamine (5). Therefore, we do not exactly know how much deferoxamine influenced the development of mucormycosis in our case. However, care should be taken to prevent mucormycosis developing in an immunocompromised host, especially those who are receiving deferoxamine for iron overload.
FIGURE LEGENDS
- Figure 1. Echocardiography showing a large mass (arrow) in the left ventricle, although it had been undetectable just 10 days before.
- Figure 2. Macroscopic pathology of the heart shows a giant thrombosis in the left ventricle.
- Figure 3. Histological examination of the left ventricular thrombosis demonstrates broad irregular hyphae, which are characteristic of mucormycosis. (left panel: PAS stain, right panel: Grocott's stain, original magnification X400)
REFERENCES
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3. Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Cantinieaux B, Verdonck A, et al. Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. J Clin Invest 1993; 91:1979-86.
4. Nosari A, Oreste P, Montillo M, Carrafiello G, Draisci M, Muti G, et al. Mucormycosis in hematologic malignancies: an emerging fungal infection. Haematologica, 2000; 85: 1068-71.
5. Wohlrab JL, Anderson ED, Read CA. A patient with myelodysplastic syndrome, pulmonary nodules, and worsening infiltrates. Chest, 2001;120: 1014-17.
