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Aspergillus osteomyelitis (osteitis)

Contents

• Invasive Aspergillus otitis
• Aspergillosis of the skull
• Aspergillosis of the sternum
• Vertebral body aspergillosis and discitis
• Epidural abscess
• Long bone and rib aspergillosis

A number of discrete clinical entities comprise aspergillosis of bone. These include mastoiditis, orbital, cranial or base of skull involvement, sternal wound infection, vertebral osteomyelitis or infection of a long bone or other peripheral site. Aspergillus infection of bone is diagnosed by isolation of Aspergillus from an open or needle biopsy with or without histological confirmation. Common underlying diseases are chronic granulomatous disease, transplantation or trauma (including surgery). Each entity will be reviewed separately. The surgical approach to therapy is summarised in the table below.

Patterns of and surgical approach to Aspergillus osteomyelitis

All patients require medical therapy

Invasive Aspergillus otitis

Aspergillus mastoiditis follows from invasive Aspergillus otitis (Petrak et al., 1985; Bickley et al., 1988; Cunningham et al., 1988; Stanley et al., 1988; Denning et al., 1989; Philips, et al. 1990; Reiss et al. 1991; Strauss & Fine, 1991; Hanna et al., 1993; Gordon & Giddings 1993). Typically this occurs in immunocompromised patients such as those with leukaemia or AIDS, but has also been reported in non-immunocompromised patients. Clinical features are variable but include otalgia, hearing loss, facial nerve paralysis, fever and otorrhea. Usually the middle ear is destroyed and infection has extended into the mastoid and/or petrous bone. Surgical debridement and antifungal therapy with amphotericin B or itraconazole may be curative, but extension into brain or an intercurrent infection is common and may be fatal.

Aspergillosis of the skull

Extension of disease beyond the confines of the sinuses in invasive Aspergillus sinusitis is usual and may be extensive with penetration through the orbital floor into the orbit or posteriorly to the orbital apex or destruction of the medial walls of the sinuses (images of Aspergillus sinusitus ). Occasionally penetration directly into the brain through the lateral wall of the sphenoid sinus or frontal sinus is seen. Rarely the anatomical boundaries of the bone are preserved and what is seen is extensive involvement of the base of the skull (Kountakis et al., 1997; Swift & Denning, 1998). Surgical debridement of bone is either not possible or incomplete and thus prolonged antifungal therapy with itraconazole is appropriate. Serum concentrations of itraconazole should be monitored.

Aspergillosis of the sternum

Following cardiac surgery, including transplantation, occasional cases of aspergillosis of the sternum are reported, often presenting weeks or months after surgery (Attah et al., 1979; Wellens et al., 1982; Frank et al., 1988; Dupont & Drouhet, 1987; Walker & Pate, 1991; Hanna et al., 1993; Barzaghi et al., 1994; Bianchi et al., 1994). Typically there is either a localised abscess just to one side of the sternum or a persistent wound over the sternum. Rarely infection arising in the mediastinum tracks out through the sternum. As the sternum is usually wired together, localised infection around the wires is frequent. Delineation of extent of disease by CT scan is appropriate, followed by debridement, removal of wires in the area of infection and antifungal therapy.

Vertebral body aspergillosis and discitis

Probably the most common manifestation of Aspergillus osteomyelitis is vertebral body disease with or without discitis (Seligsohn et al, 1977; Seres et al., 1972; Ingwer et al., 1978; Tack et al., 1982; Chee & Poh, 1983; Mauk et al., 1983; McKee et al., 1984; Nasca et al., 1985; Brown et al., 1987; Wagner et al., 1985; Holmes et al. 1988; Simpson et al., 1988; Morganlander et al. 1989; Bridwell et al., 1990; Govender et al., 1991; Peters-Christodoulou et al, 1991; Hummel et al., 1993; Assad et al., 1994; Kline et al., 1994). In some patients this represents dissemination from a distant, often clinically silent, source. This is most common in patients with chronic granulomatous disease or those treated with corticosteroids, including transplant patients. In the former many vertebrae may be involved, whereas only one or two are typically affected in the latter. Less commonly patients with chronic necrotising bronchopulmonary aspergillosis treated with corticosteroids or diabetics will have direct extension of the pulmonary process into the vertebral column. Rarely, vertebral osteomyelitis may follow back surgery and be the result of Aspergillus contamination of the surgical field (Tack et al., 1982).

Epidural abscess

In a small proportion of these cases, extension of aspergillosis into the epidural space is seen leading to spinal cord compression ( Seres et al., 1972; Ingwer et al., 1978; Chee & Poh, 1983; Mawk et al., 1983; McKee et al., 1984; Barnwell et al., 1985; Ferris & Jones, 1985; Wagner et al., 1985; Simpson t al, 1985; Korovessis et al., 1994) . Decompressive surgery is urgently indicated if disease is limited in extent. Only rarely does Aspergillus actually invade the spinal cord (Ingwer et al., 1978).

Simple debridement is the usual initial approach, but a radical debridement followed by bone grafting with, for example, a rib strut has been successful. Sometimes instability is such that Harrington rods are necessary. In previous cases, the timing of surgery has been variable, being undertaken as late as 5 months after diagnosis. Late surgery is indicated for instability or failure on therapy.

Long bone and rib aspergillosis

Long bone and rib aspergillosis appears to be a disease almost exclusively restricted to patients with chronic granulomatous disease (CGD) (Bujak et al., 1974; Casscells et al., 1978; Corrado et al., 1980; Cohen et al., 1981; Lazzarin & Capsoni, 1982) with rare exceptions (Corrall et al., 1982; De Vuyst et al, 1992 Sonin et al., 1996, Cimerman et al., 1999). The only exception is those who have suffered a penetrating injury or extensive soft tissue injury. In traumatic cases surgical debridement together with antifungal therapy are critically important in control of disease. In CGD the need for radical surgery is not so clear. The pathology shows few hyphae and multiple large giant cells with hyphae within. In many patients with CGD, extensive bony disease is often present and surgical debridement would lead to permanent deformity or instability. In these cases high dose itraconazole therapy for months or years (or amphotericin B therapy if serum concentrations are inadequate) is usually successful, but takes a long time.

Overall there appears to be an advantage of surgical therapy in the treatment of bony aspergillosis (Denning & Stevens, 1990). However this could reflect the extent of disease and surgical feasibility or the necessity to operate on medical failures. It could also reflect rapid accurate diagnosis. The tissue concentrations of itraconazole in bone are two-to three-fold higher than plasma (Heykants et al., 1989) and this may be an important factor in the relative success of itraconazole for Aspergillus osteomyelitis (Dupont & Doubet, 1987; de Buele et al., 1988; Denning et al., 1989; Sachs et al, 1990; Peters-Christodoulou et al., 1991; Pasic et al., 1996; Witzig et al., 1996). A daily dose of 400 mg is appropriate. Many months of therapy, typically 6 to 18 is appropriate. Amphotericin B does not penetrate bone well (Denning & Stevens 1990). If itraconazole therapy cannot be used or fails, a daily dose of 0.8 to 1.0 mg/kg is appropriate initially, e.g. for the first 2 to 4 weeks. After this, a daily dose of 0.5 mg/kg (or 1.0mg/kg on alternate days) is likely to be successful if continued for at least 12 weeks.

Lipid-associated amphotericin offers a possible pharmacodynamic advantage over amphotericin B as these compounds are less toxic and a longer duration of therapy is possible. Doses of at least 3 mg/kg are appropriate.

It is not known if hyperbaric oxygen (Kountakis et al. 1997) or interferon-gamma (Heinrich et al., 1991; Kline et al., 1994; Pasic et al. 1996) are of value in the treatment of Aspergillus osteomyelitis. Interferon-gamma has only been used in children with chronic granulomatous disease.

David W. Denning FRCP FRCPath FIDSA FMedSci
Professor of Medicine and Medical Mycology
Director, National Aspergillosis Centre
Education and Research Centre
University Hospital of South Manchester (Wythenshawe Hospital)
Southmoor Road
Manchester M23 9LT UK

June 1999