Rhino-Orbitocerebral Zygomycosis Caused by Conidiobolus incongruus in an Immunocompromised Patient in Germany

Abstract

Mucorales (subphylum Mucoromycotina) are well-known agents of invasive mucormycosis, whereas Entomophthorales (subphylum Entomophthoromycotina) are rarely encountered in human diseases in temperate zones. Here we report a fatal case of invasive rhino-orbitocerebral entomophthoramycosis caused by Conidiobolus incongruus in a 78-year-old woman with myelodysplastic syndrome. CASE REPORTA 78-year-old woman with known hypoplastic myelodysplastic syndrome (MDS) with trilinear pancytopenia was admitted to our hospital for further evaluation and treatment of refractory fever. Two months earlier she had been diagnosed with hypoplastic MDS without cytogenetic alterations. Because of her good clinical presentation and her age, chemotherapy was not initiated. Other known comorbidities were arterial hypertension and non-insulin-dependent diabetes mellitus without signs of hyperglycemia. Five weeks before admission, she had developed cellulitis on the right side of the forehead and treatment with cefuroxime intravenously (i.v.) (3 doses of 1.5 g/day) had been initiated, because of an initial swab from which methicillin-sensitive Staphylococcus aureus was cultured. At the time of referral, the patient was in a reduced general state of health and she was unable to open the right eye. Hemogram showed leukocyte counts of 700/l, a hemoglobin level of 6.9 g/dl, thrombocyte counts of 2,000/l, and a C-reactive protein level of 476 mg/liter. Blood cultures remained sterile. Galactomannan and (133)-beta-D-glucan detection in serum was attempted repeatedly with negative results. However, fever persisted and antibiotic therapy was switched to piperacillintazobactam i.v. (3 doses of 4.5 g/day) and finally to imipenem i.v. (3 doses of 1 g/day). Trimethoprim-sulfamethoxazole orally (p.o.) (2 doses of 960 mg twice per week) was given regularly as anti-Pneumocystis jirovecii prophylaxis, and fluconazole (1 dose of 200 mg/day p.o.) was given as antimycotic prophylaxis. Supportive therapy with granulocyte colony-stimulating factor and transfusion of erythrocytes and thrombocytes were started, but cellulitis progressed. A computed tomography (CT) scan of the skull and midface showed frontal hypodensity, suggestive of intracerebral abscess formation; signs of pansinusitis; and periorbital edema with orbital inflammation (Fig. 1A). Sinus surgery was performed. Samples of all affected bones were sent for microbiological and pathological examination. Anti-infective therapy was changed to levofloxacin i.v. (1 dose of 500 mg/day) and liposomal amphotericin B i.v. (1 dose of 200 mg/day). Histological examination of the ethmoidal cells revealed a chronic inflammatory infiltrate containing lymphocytes, plasma cells, and a few dispersed granulocytes. Hyphae with almost orthogonal branches, which invaded the mucosal stroma, were seen (Fig. 1B). Invasion into the bones or vascular structures could not be verified. No signs of SplendoreHoeppli phenomenon were found.Direct fluorescence microscopy using calcofluor white (fluorescent fungal cell wall stain; Bay...

Human Fungal Pathogens of Mucorales and Entomophthorales

“…C. incongruus infection has been also diagnosed in sheep, causing rhinofacial infection (Ketterer et al 1992), and in a deer, causing systemic dissemination (Madson et al 2009). Thus, C. incongruus more commonly causes disseminated infections and seldom causes localized infection, a clinical feature in contrast to that of C. coronatus (Walker et al 1992;Walsh et al 1994;Wuppenhorst et al 2010).…”

“…The first recorded case of C. incongruus infection in humans was diagnosed by Gilbert et al in 1970, but the recovered organism was properly identified 6 yr later by King and Jong (1976). C. incongruus infections have been diagnosed in both apparently normal and immunocompromised hosts (Walsh et al 1994;Wuppenhorst et al 2010). An important difference between C. incongruus and the other pathogenic Conidiobolus species is the clinical presentation of the infection.…”

“…The majority of diagnosed cases, some fatal, show systemic involvement of several internal organs (Busapakum et al 1983;Ketterer et al 1992;Hernandez et al 2007). Since the first report, at least three more patients have been diagnosed with orbitofacial and orofacial conidiobolomycosis (Eckert et al 1972;Busapakum et al 1983;Al-Hajjar et al 1996), and nine systemic cases involving one or more organs have been reported (Eckert et al 1972;Busapakum et al 1983;Walsh et al 1994;Hernandez et al 2007;Wuppenhorst et al 2010). C. incongruus infection has been also diagnosed in sheep, causing rhinofacial infection (Ketterer et al 1992), and in a deer, causing systemic dissemination (Madson et al 2009).…”

Infections in myelodysplastic syndromes

“…Although the rarity of those infections may have encouraged reports being made. [85][86][87][128][129][130][131][132][133][134][135][136][137][138] A relationship with the iron overload often seen in MDS cannot be ruled out, as iron overload is a known risk factor for zygomycosis infection (see above). In some cases, zygomycosis was observed at diagnosis of MDS.…”

“…In some cases, zygomycosis was observed at diagnosis of MDS. 137,138 A significant number of patients had additional co-factors for zygomycosis, including diabetes, 137,138 obstructive bronchial pneumonia, 137 and treatment with deferoxamine. 85,87 In some cases, the clinical presentation was atypical, 139 with unusual features like spinal cord 131,135,140 or coronary artery obstruction.…”