gms | German Medical Science

Rhino-cerebral-orbital mucormycosis and aspergillus infections are aggressive fungal infections with a high mortality rate. They frequently develop in immunocompromised patients. Most cases of invasive fungal rhinosinusitis are caused by aspergillus fumigatus and mucoraceae species. Of the almost 900 species of aspergillus, the most often found in human diseases is aspergillus fumigatus. An aspergillus fumigatus infection of the paranasal sinuses and/or orbita can be invasive or non invasive. Mucormycosis is the second most frequent mycosis, which is caused by filamentous fungi. The most typical clinical manifestations are rhino-cerebral, the maxillo-facial and the pulmonal mucormycosis. Rhinocerebral mucormycosis starts in the nose or oral cavity and infiltrates the paranasal sinuses, orbita or the brain over the orbital apex or the cribriform plate.

Most patients with fungal rhinosinusitis present first only unspecific symptoms like headache, nasal discharge or nasal obstruction. Often they come late with progedient symptoms and show already complications like orbital involvement with proptosis, ophthalmoplegia or intracerebral spread with meningitis or brain abscess.

We present an 83-year-old male patient with diabetes mellitus, who complains about rapid loss of vision, proptosis bulbi and ophthalmoplegia. A computed tomography scan of the paranasal sinuses revealed a hypodense, expansive mass involving the left ethmoid cells and the orbita (Figure 1 [Fig. 1]) The patient was treated by endonasal ethmoidectomy and orbital decompression on the left side. Magnetic resonance imaging confirmed the findings. Histological specimens of the ethmoid sinus showed the typical hyphea from aspergillus fumigatus. He got a postoperative antifungal therapy with Itraconazol (1 week 600 mg/d; 3 weeks 400 mg/d; after 4. week 200 mg/d) for 3 months. The ophthalmoplegia recovered and the visus was slightly reversible.

A second patient presented to us by our oncologic department with progressive proptosis bulbi. His medical history was notable for acute leucaemia, status after polychemotherapy and bone marrow transplantation The magnetic resonance imaging showed an opacification of the left ethmoid cells and an extension to the orbital apex (Figure 1 [Fig. 1]). We treated the patient with transfacial ethmoid-sphenoidectomy and an orbital decompression on the left side. Hematoxylin-eosin stained specimen demonstrated nasal mucosa with polymorphonuclear and lymphatic infiltration, edema and necrosis. Fungal hyphae from mucoraceae were also identified. Despite antimycotic treatment with amphotericin B there was a progression in the fungal disease especially in the orbital apex. The following extensive surgery included an orbital exenteration on the left side. In spite of this treatment the patient developed a brain abscess and died 3 month after his first presentation in our department.

A 48-year-old male with hodgkin lymphoma was admitted to our department in december 2000 with the suspicion of a tumour of the paranasal sinuses. His medical history included in May 2000 the diagnosis of invasive pulmonal aspergillosis, treated with intravenous amphotericin B and then orally with itraconazol.

Now a computed tomography scan of the paranasal sinuses revealed an involvement of both sphenoid sinuses (Figure 1 [Fig. 1]). He underwent transnasal navigated endonasal debridement, including adjacent soft tissue of ethmoid and sphenoid sinuses mucosa. The histological specimens show the typical hyphae of aspergillus fumigatus. Subsequently the patient was treated with amphotericin B. From January 2001 up to now there is no evidence of hodgkin lymphoma or of the pulmonal or sinusoidal aspergillosis.

The forth patient was a 68-year-old male with a myelodysplastic syndrome since August 2004. The chemotherapy included a treatment with Cyclosporin A and Antimyozytenglobulin (ATG). In September 2004 he was presented to us by our oncologic department with sinusitis paranasalis. The CT scans revealed an opacification of the right ethmoid cells. In October 2004 he underwent transnasal ethmoid- and sphenoidectomy. The histological specimens show a mucormycosis with osteomyelitis An intravenous amphotericin B treatment was started. In December 2004 and April 2005 there was a progression of the mucormycosis infection of the right ethmoid cells including an orbital involvement (Figure 1 [Fig. 1]). The patient was treated in December and April with a radical sinus debridement. After the discussion of these case in our interdisciplinary skull base conference, the patient underwent a antifungal treatment with the new substance posaconacol in a specialised centrum in Germany.

Both, aspergillosis and mucormycosis are rare filamentous fungal infections, which predominantly arise in immunocompromised patients (survival rate 20–40%; [Ref. 4]). The underlying disease of patients with an immune defect often masks the symptoms. This makes the diagnosis of fungal infection more difficult. Therefore they have no typical symptoms of the disease, rather non-specific sinusitis complaints like headache, rhinorrhoe, nasal obstruction and fever. For both kinds of fungi, the fulminate process with rapid infiltration of the neighbouring tissues like the orbita and the rhinobasis is typical. For the identification of the bony destruction a CT is crucial. MRI provides early detection of meningeal or intraparenchymal spread and intracranial vascular occlusion. The definite diagnosis can only be verified by histological examination. The best way to detect the typical hyphae is by freezing and paraffin sections [Ref. 4], [Ref. 7], [Ref. 8]. No consensus has been reached as to the most appropriate course of management in cases of chronic invasive fungal rhinosinusitis, but most reports recommend a combination of surgical debridement of the devitalised tissue and systemic antifungal therapy. The most important therapy, however, is the identification and reversal of the source of immunocompromisation [Ref. 6]. Amphotericin B is the most widely accepted medication in the treatment of this condition. But the therapeutic activity of amphotericin B is limited by its potentially severe side effects like renal and hepatic toxicity, anaemia and electrolyte abnormalities [Ref. 1], [Ref. 2]. Furthermore it must be taken in account that amphotericin B does not penetrate the blood brain barrier, so it can be ineffective in cerebral fungal infections. Liposomal amphotericin B represents a possible alternative to conventional amphotericin B because it penetrates the brain parenchyma and results in high drug concentration in the brain [Ref. 5]. Hyperbaric oxygen therapy has also been suggested for combination therapy [Ref. 2], [Ref. 3], [Ref. 7]. Expanded procedures as orbital exenteration have to be considered in individual cases especially with presence of ophtalmoplegia and blindness. Orbital exenteration is not mandatory in all patients with evidence of orbital involvement in whom the underlying cause of the immunodeficiency is reversible [Ref. 1]. In conclusion, a successful treatment is based on early diagnosis, control of underlying diseases, surgical resection, systemic administration of antifungal drugs. To avoid a delay in treatment, it is absolutely necessary to consider the possibility of a fungal infection!