Clinicotherapeutic conference

Fatal Rhino-Orbito-Cerebral Zygomycosis Caused by Apophysomyces elegans in a Healthy Patient

Apophysomyces is a rare fungal organism causing rhino-orbito-cerebral mycotic infections with high morbidity and mortality, typically in immunocompetent individuals. Several cases of Apophysomyces elegans orbital disease have been reported. Herein, we report a case of Apophysomyces variabilis infection involving the orbit, sinuses, and calvarium in an immunocompetent 74-year-old woman, with a review of the literature. Unlike prior cases of A. elegans classic rhino-orbito-cerebral infection, our case included diffuse calvarial lytic lesions and overlying soft tissue nodules, but without parenchymal intracranial involvement. There was radiographic and clinical evidence of infarction of the orbital contents and cavernous sinus thrombosis. Anastomoses between the superior orbital (ophthalmic) vein and diploic veins of the calvarium are believed to be primarily responsible for the unusual mode of spread on the extradural surface of the brain. Although the patient stabilized without definitive surgical intervention, her disease slowly and intermittently progressed for over a year after presentation, requiring multiple courses of antifungal treatment.

Mucormycosis, also known as Zygomycosis and Phycomycosis, is a rare opportunistic fungal infection with a fulminant course and high mortality rate. Its Rhinocerebral variant is an acute invasive fungal infection which normally affects immunocompromised patients with uncontrolled diabetes, organ transplant and hematological malignancies. It may pose a therapeutic challenge considering the fact that its onset may be followed by rapid progress, extensive involvement and rapid clinical deterioration which may even be fatal. With due regard to such nature of the disease, early diagnosis and aggressive treatment become the cornerstone for better prognosis and survival. Vigilance on the part of the clinician to include Rhinocerebral Mucormycosis as part of the differential diagnosis in susceptible hosts with sino-orbital involvement holds the key. A multimodal treatment strategy comprising of early diagnosis, reversal or stabilization of underlying medical condition, systemic antifungals and surgical debridement has shown best results. This paper reviews the literature on Rhinocerebral Mucormycosis and presents a series of seven cases with their varying predisposing conditions, clinical manifestations and treatment outcome, thus adding to the bank of knowledge on this emerging threat.

To review the current literature on mucormycosis in immunocompentent/otherwise healthy individuals, to which five new cases with maxillary sinus involvement have been added.

We searched in the PudMed database all articles in the English language related to human infections caused by fungi of the order Mucorales, in immunocompetent/otherwise healthy patients, starting from January 1978 to June 2009. In addition, we updated the literature by reporting five new cases diagnosed and treated at the oral medicine unit of our institution.

The literature review showed at least 126 articles published from 35 different countries in the world, to a total of 212 patients described. The most affected country was India with 94 (44.3%) patients and the most representative clinical form was the cutaneous/subcutaneous with 90 (42.5%) patients. Our five immunocompetent patients with a diagnosed infection of Mucorales localized at the maxillary sinus completely healed with lyposomial amphotericin B.

The literature analysis revealed that even in immunocompetent/otherwise healthy individuals mucormycosis infection has a worldwide distribution. What might be the real predisposing factors involved in its pathogenesis in such patients and the real causes of this peculiar geographic distribution still remains unknown. It is likely that, in our cases, a chronic insult of a well-defined and localized body area might have resulted in a local immunocompromission, thus fostering the development of an invasive fungal infection.

Zygomycetes are filamentous fungi with a worldwide distribution. This class of fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales. Members of the latter are associated with chronic cutaneous and subcutaneous infections that are limited to the tropics and rarely disseminate to internal organs. The order Mucorales includes several species involved in rhinocerebral, pulmonary, cutaneous, gastrointestinal and other less frequent infections in immunocompetent and immunocompromised individuals, and is characterized by a tendency to disseminate. Portals of entry of zygomycetes are usually the lungs, skin, and gastrointestinal tract. A characteristic property of zygomycetes is their tendency to invade blood vessels and to cause thrombosis—processes that result in subsequent necrosis of involved tissues. Risk factors associated with zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes of age, and intravenous drug abuse. Recently, the widespread use of voriconazole for prophylaxis or treatment of aspergillosis in patients with haematological malignancies has been linked with a rise in the numbers of cases of invasive zygomycosis. As the symptoms, clinical signs and imaging findings of these infections are non-specific, a high index of suspicion is required for timely diagnosis. Early diagnosis, correction of the underlying predisposing factors, aggressive surgical debridement of all infected tissues and lengthy administration of antifungals are the only potentially curative options for this rare but emerging invasive fungal infection.

Aspergillosis and candidosis remain the most prevalent opportunistic fungal infections in immunocompromised patients, but diseases caused by the Zygomycetes have become of increasing importance. Exposure to antimycotic drugs with no activity against zygomycetes may be a new risk factor and an explanation for the increasing incidence of zygomycosis. The latter infection occurs only rarely in immunocompetent hosts, but in recent years Apophysomyces elegans has been described in many subtropical countries as an emerging pathogen causing mostly cutaneous infections after traumatic inoculation.