View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW 10.1111/j.1469-0691.2009.02989.x Orbitomaxillary mucormycosis (zygomycosis) and the surgical approach to treatment: perspectives from a maxillofacial surgeon A. D. Rapidis Department of Maxillofacial Surgery, Greek Anticancer Institute, St. Savvas Hospital, Athens, Greece Abstract Rhinocerebral or rhino-orbitocerebral (mucormycosis) zygomycosis (ROCZ) usually occurs among patients with poorly controlled diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload or extensive burns, in patients undergoing treat- ment with glucocorticosteroid agents, or in patients with neutropenia related to haematologic malignancies. The disease process starts with inhalation of the fungus into the paranasal sinuses. The fungus may spread to invade the palate, sphenoid sinus, cavernous sinus, orbits or cranially to invade the brain. Pain and swelling precede oral ulceration and the resulting tissue necrosis can result in palatal perforation. Infection can sometimes extend from the sinuses into the mouth and produce painful, necrotic ulcerations of the hard palate. If untreated, infection usually spreads from the ethmoid sinus to the orbit, resulting in the loss of extraocular muscle function and proptosis. Surgical treatment includes the resection of involved tissues of the face, including skin and muscle, any skin of the nose that is involved, maxillary and ethmoid sinuses, necrotic tissue of the temporal area and infratemporal fossa, and orbital exenteration. The keys to successful therapy include suspicion of the diagnosis and early recognition of the signs and symptoms, correction of under- lying medical disorders such as ketoacidosis, and aggressive medical and surgical intervention. Keywords: Maxillectomy, mucormycosis, orbital exenteration, zygomycosis Clin Microbiol Infect 2009; 15 (Suppl. 5): 98–102 ity of cases reported have represented either isolated Corresponding author and reprint requests: A. D. Rapidis, examples or small, retrospective series. This relative scarcity Department of Maxillofacial Surgery, Greek Anticancer Institute, St. Savvas Hospital, 171 Alexandras Avenue, Athens 115 22, Greece of cases hinders the drawing of diagnostic and therapeutic E-mail: [email protected] conclusions [4]. However, with the increasing prevalence of diabetes and immunosuppressive conditions, mucormycosis has emerged as an important fungal infection. Based on clini- cal presentation and the involvement of a particular anatomic Introduction site, mucormycosis can be divided into at least six clinical categories: (i) rhinocerebral; (ii) pulmonary; (iii) cutaneous; Zygomycetes have a wide geographical distribution, are all (iv) gastrointestinal; (v) disseminated, and (iv) miscellaneous thermo-tolerant, and utilize a variety of nutritional sub- [5,6]. strates. In nature, they are found in the soil, animal faeces and decaying plant materials [1,2]. They spread by the pro- Risk Factors and Pathophysiology of duction of sporangiospores that are released into the envi- Rhinocerebral or Rhino-orbitocerebral ronment as airborne propagules. Humans are usually Zygomycosis resistant to the disease because Mucorales fungi are ubiqui- tous in the environment. Nosocomial infections can occur from sporangiospores released through contaminated air- Rhinocerebral or rhino-orbitocerebral zygomycosis (ROCZ) conditioning systems or contaminated wound dressings. The usually occurs among patients with poorly controlled diabe- fungus exhibits a remarkable affinity for arteries and grows tes mellitus (especially those with ketoacidosis), solid malig- along the internal elastic lamina, causing thrombosis and nancies, iron overload or extensive burns, or in patients who infarction. Infections occur equally in both sexes, irrespective take glucocorticosteroid agents or have neutropenia related of age. to haematologic malignancies. A recently identified important Mucormycosis, also known as zygomycosis and phycomy- clinical feature is the increased susceptibility to mucormyco- cosis, was first described by Paultauf in 1885 [3]. The major- sis of patients with elevated available serum iron. It has been ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases CMI Rapidis Surgical approaches to orbitomaxillary mucormycosis 99 known for two decades that patients treated with the iron media. This direct invasion and dissection by the fungus chelator deferoxamine have a markedly increased incidence causes extensive endothelial damage, resulting in thrombus of invasive mucormycosis [7, 8]. However, it is now clear formation and ischaemia to the surrounding tissues. The that iron chelation is not the mechanism by which deferox- infarcted tissue creates an environment that promotes fungal amine enables mucormycosis infections. Although deferox- proliferation and the resultant poor vascular supply prevents amine is an iron chelator from the perspective of the human systemic medical therapy from eradicating the fungus. The host, Rhizopus spp. actually utilize deferoxamine as a sidero- nasal and sinus walls are invaded via these vessels and the phore to supply previously unavailable iron to the fungus. orbit is invaded secondarily via freely communicating fora- Patients with diabetic ketoacidosis are at high risk of devel- men and venous channels. The fungus invades the cranium oping rhinocerebral mucormycosis. Multiple lines of evidence through either the orbital apex or the cribriform plate of the support the conclusion that patients with systemic acidosis ethmoids and ultimately kills its host [14,15]. have elevated levels of available serum iron, probably as a result of the release of iron from binding proteins in the Clinical Symptoms and Signs presence of acidosis [9]. Neutropenia is another significant risk factor. The correction of neutropenia with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage The initial symptoms of ROCZ are consistent with either colony-stimulating factor (GM-CSF) is important to improve sinusitis or periorbital cellulitis and include eye or facial outcome. A breakthrough in the management of zygomycosis pain and facial numbness, followed by the onset of conjunc- in patients with neutropenia was recently achieved with tival suffusion, blurry vision and soft tissue swelling. Symp- empirical voriconazole therapy in the absence of ampho- toms that may suggest mucormycosis in susceptible tericin B (AmB) [10,11]. Initiation of early and appropriate individuals include multiple cranial nerve palsies, unilateral antifungal administration and, if required, discontinuation of periorbital facial pain, orbital inflammation, eyelid oedema, steroids or deferoxamine is advisable [12]. blepharoptosis, proptosis, acute ocular motility changes, Rhinocerebral mucormycosis continues to be the most internal or external ophthalmoplegia, headache or acute common form of the disease, accounting for between one- vision loss. Fever is variable and may be absent in up to third and one-half of all cases of mucormycosis. Approxi- half of the cases. White blood cell counts are typically ele- mately 70% of rhinocerebral cases (occasionally referred to vated, as long as the patient has functioning bone marrow as craniofacial cases) occur in diabetes patients with keto- [16,17]. acidosis. More rarely, rhinocerebral mucormycosis has also Upon visual inspection, infected tissue may appear normal occurred in patients who have received a solid organ trans- during the earliest stages of spread of the fungus. Infected plant or those with prolonged neutropenia. Recently, rhino- tissue then progresses through an erythematous phase, with cerebral disease has become an increasing problem in or without oedema, before the onset of a violaceous appear- patients undergoing haematopoietic stem cell transplantation. ance and, finally, the development of a black, necrotic eschar These cases have largely been associated with steroid use as the blood vessels become thrombosed and tissue infarc- for graft vs. host disease [13]. tion occurs. Palatal involvement is usually the result of the Infection with Zygomycetes can be acquired by inhalation, direct extension of disease from the maxillary sinus and in ingestion or the deposition of spores in wounds. The fungi the distribution of the sphenopalatine and greater palatine give rise to pathogenic lesions as a result of invasion and arteries. Pain and swelling precede oral ulceration, and the growth within the lumen and walls of major blood vessels, resulting tissue necrosis can result in palatal perforation. with ensuing thromboembolism resulting in ischaemia and tis- Infection can sometimes extend from the sinuses into the sue necrosis. Agents of zygomycosis have a predilection for mouth and produce painful, necrotic ulcerations of the hard the internal elastic lamina of the arterial blood vessels and palate. If untreated, infection usually spreads from the eth- spread by angioinvasion. The disease process in the ROCZ moid sinus to the orbit, resulting in loss of extraocular mus- form probably starts with the inhalation of the fungus into cle function and proptosis. Marked chemosis may also be the paranasal sinuses. Upon germination, the fungus may seen. The infection may rapidly extend into the neighbouring spread inferiorly to invade the palate, posteriorly to invade tissues [18]. the sphenoid sinus and beyond into the cavernous