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R. Gattringer (1), N. Koperek (2), B. Willinger (3), W. Graninger (1), E. Presterl (1,3)

(1) Med. Universität Wien - Innere Medizin I
Abt. für Infektionen & Tropenmedizin
Währinger Gürtel 18-20
A – 1090 Wien
Tel: +43/1/40400-4440
E-Mail: elisabeth.presterl@meduniwien.ac.at

(2) Abt. für Klin. Pathologie
(3) Institut für Hygiene und Med. Mikrobiologie
Abt. für Klin. Mikrobiologie

Background: Invasive aspergillosis is a severe complication occurring most commonly in neutropenic patients with leukemia or bone marrow transplantation. We describe the course and the antifungal treatment of in a non-neutropenic patient with generalized aspergillosis.Case report: A 63-year old woman with renal Wegener’s granulomatosis developed fever refractory to imipenem, vancomycin and fluconazole after 3-months treatment with cyclophospamid (1 g/ every 4 weeks) and prednisolon 0.5 – 1 mg/kg. A CT scan showed abscesses in the thyroid gland besides unspecific infiltrates within both lungs. The aspiration of a thyroid abscess yielded the growth of Aspergillus flavus. The patient did not respond to the treatment of voriconazole and was transferred to our hospital.

The patient was in a reduced general condition with a normal neutrophil count, a slightly elevated serum creatinine and no signs of active Wegener’s granulomatosis. A MRT of the skull revealed a lesion in the brain compatible with cerebral aspergillosis. The CT scan of the lung was suggestive for pulmonal aspergillosis. A combination therapy with amphotericin B (1 mg/kg/24 h) plus caspofungin 50 mg/d was started. All immunosuppressive treatment was stopped.The patient’s condition improved. However she complained of increasing nausea and absolute loss of appetite. Thus parenteral nutrition was started. Eight weeks after initiation of therapy, the cerebral lesion was slightly smaller, the pulmonal lesions were increasing. Additionally, subcutaneaous nodules and abcesses in the myocardium were detected. Artificial respiration had to be started because of respiratory failure. A further aspiration of the still existing thyroid abscesses revealed masses of hyphal elements but no growth in the fungal culture. Panfungal PCR hinted the presence of an ascomycete other than Aspergillus. The antifungal therapy was switched to amphotericin B plus voriconazole, then to oral posaconazole. The patient improved.

Because of increasing cholestasis, posaconazole was stopped after 3 weeks.
The patient died 14 days later. The autopsy revealed suppurative cholangitis, the cultures are still pending.
Discussion: Generalized aspergillosis is considered a disease in neutropenic patients. However, in severely immunosuppressed patients multifocal fungal disease caused by more than one fungal species may develop.