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Mucormycosis S Afr Optom 2008 67(1) 36-41 Mucormycosis ‡ SD Mathebula Department of Optometry, University of Limpopo, Private Bag x 1106, Sovenga, 0727 South Africa <[email protected]> Received 8 December 2007; revised paper accepted 31 March 2008 Abstract of uniformity in this text, although zygomycosis and The zygomycoses are infections caused by phycomycosis are also accepted. Mucormycosis is a fungi of the class zygomycetes, comprised of the rare but fatal or aggressive, opportunistic infection of orders Mucorales and Entomophthorales. Fungi of the sinuses and brain caused by saprophytic aerobic this order are causes of mucormycosis, an acute op- fungi of the phycomycetes, order Mucora- portunistic infection occurring mostly in immuno- les.3 − 5 Among the Mucorales, Rhizopus and Mucor are compromised individuals, particularly in patients the common causes of human infections. with diabetic ketoacidosis. The purpose of this Phycomycetes (Zygomycetes) are common through- paper is to present an academic perspective on the out the environment and in bread mould, soil, ma- pathophysiology, presentation and management of nure, decaying fruit and vegetables, and are frequent- mucormycosis. Possible management strategies are ly found colonizing the oral mucosa, nose, paranasal provided. sinuses and throat, where massive spore formation occurs.7 , 8 Inhalation is the natural route of infection. Keywords: amphotericin, diabetes ketoacidosis, Infection progresses as the hyphae begin to invade mucormycosis, phycomycosis, zygomycosis blood vessels and causes erosion of the bone through walls of the nasal and maxillary sinuses. Extension to Introduction ethmoid sinuses can lead to orbital and retro-orbital Mucormycosis 1 , also known as zygomycosis or involvement. Intracranial involvement also occurs phycomycosis was first described by Paultauf in from invasion by way of the superior orbital fissure, 1885. He documented involvement of the central ophthalmic vessels and cribriform plate, through the nervous system for the first time, and coined the term carotid artery or possibly via a perineural route. 7− 10 “mycosis mucorina” which later became “mucormy- cosis.” In 1959, Lie-Kian-Joe, et al. 2 proposed that Pathogenesis the disease be designated “phycomycosis” rather than “mucormycosis”, since they found that fungi belong- Host defences ing to orders other than the Mucorales (such as En- Both mononuclear and polymorphonuclear phago- tomophthorales, Zoopagales and Kickxellales) were cytes of the normal host are the major defence mecha- pathogenic to man. Since then the term phycomycosis nism against mucormycosis. They kill Mucorales by has become widely accepted. The term “zygomyco- the generation of oxidative metabolities and the sis” includes both mucormycosis and entomophtho- cationic peptides defensins. 11 − 14 Organisms of this ramycosis, the latter being a tropical infection of the family of saprophytic fungi are ubiquitous, infecting subcutaneous tissue or paranasal sinuses caused by humans whose systemic health is compromised (dys- species of Basidiobolus or Conidiobolus. 3 − 5Mucormy- functional phagocytes). Several predisposing cosis is the terminology that will be used for the sake ‡ BOptom(UNIN) MOptom(UNIN) 36 The South African Optometrist S Afr Optom 2008 67(1) 36-41 SD Mathebula - Mucormycosis conditions, such as diabetes, leukemia, lymphoma, even when appropriate treatment has been instituted. AIDS, chemotherapy, severe burns, malnutrition and Based on clinical presentation and the involvement of uremia have been reported in the literature.1 − 10 a particular site, mucormycosis can be divided into Human infection is felt to be caused by asexual various clinical categories (rhinocerebral, pulmonary, spore formation. 1 The tiny spores become airborne cutaneous, gastrointestinal, disseminated and miscel- and land on the oral or nasal mucosal of humans. In laneous). the vast majority of immunologically competent in- Rhinocerebral mucormycosis is the most com- dividuals, these spores will be contained through mon form of the infection and predominantly occurs phagocytic response. If this fails (for example, in im- in patients with poorly controlled diabetes mellitus. munocompromised or metabolic abnormalities), ger- The high iron, glucose-rich acid milieu facilitates mination will ensue and hyphae will develop. Because fungal growth. 1 ,, 4 10 ,, 25 26 Pulmonary mucormycosis polymorphonuclear leukocytes are less effective in occurs most commonly in leukemic patients who removing hyphae, the infection can then become es- are receiving chemotherapy and patients undergoing tablished. Hyperglycemia and acidosis are known to hematopoietic stem cell transplants. 27 − 29 Pulmonary impair the ability of phagocytes to move toward and mucormycosis may develop as a result of inhalation kill the invading organism by both oxidative and non- or by hematogenous or lymphatic spread. Symptoms oxidative mechanisms (they provide an excellent en- include dyspnea, cough and chest pain. 29 Gastrointes- vironment for fungi to grow).14 tinal mucormycosis is rare but it is believed to occur in extremely malnourished children. The stomach, Role of iron colon and ileum are the most commonly involved Iron appears to be an important element in the sites.30 Hepatic mucormycosis has been associated growth factor of Mucorales. Reduced ability of the with ingestion of herbal medications. 31 Nonspecific serum to bind iron at low pH may be the basic defect abdominal pain, nausea, vomiting, fever and hema- in the body defense mechanism. 1 ,, 1 1 1 5 − 1 7 Human re- tochezia are the common symptoms. The agents of sistance to fungal infection rests on the ability to re- cutaneous mucormycosis are typically incapable of strict the availability of iron to an invading fungus by penetrating intact skin. Patients who develop cutane- binding it to proteins such as apotransferrin. Fungal ous mucormycosis are those with disruption of the hyphae produce a substance called rhizoferrin which normal protective cutaneous barrier. However, burns binds iron avidly. This iron-rhizoferrin complex is and traumatic disruption of skin enable the organisms then taken up by the fungus and becomes available to penetrate into deeper tissues. Hematologenously for vital intracellular processes, further reducing iron disseminated mucormycosis may originate from any availability for the host. primary site of infection. 8 , 11 Pulmonary mucormyco- Deferoxamine is used as a chelating agent for iron sis in severely neutropenic patients has the highest and aluminum in patients undergoing hemodialysis incidence of dissemination. Less commonly, dis- and has been associated with a fulminant form of mu- semination can arise from the gastrointestinal tract, cormycosis. 1 ,, 11 1 8 − 2 3 While deferoxamine is an iron sinuses or cutaneous lesions. The most common site chelator from the perspective of the host, Rhizopus of dissemination is the brain, but metastatic lesions spp. actually utilizes deferoxamine as a rhizoferrin may also be found in the spleen, heart, skin and other to supply previously unavailable iron to the fungus. organs. Cerebral infection following dissemination is Patients with diabetic ketoacidosis are at high risk distinct from rhinocerebral mucormycosis and results of developing mucormycosis due to an elevation in in abscess formation and infarction, patients present available serum iron. 24 with sudden onset of focal neurological deficits or coma. 11 Agents of the Mucorales may cause infection Clinical presentation in virtually any body site.1,, 8 11 The clinical hallmark of mucormycosis is vascular Other at-risk populations include immunosup- invasion resulting in thrombosis and tissue infarction pressed patients with organ transplants, possibly due (necrosis). Because of its lethal (aggressive) nature to iron overload from repeated blood transfusion death can occur within several days to a few weeks, 37 The South African Optometrist S Afr Optom 2008 67(1) 36-41 SD Mathebula - Mucormycosis and graft-versus-host disease treated with steroids, pa- Imaging techniques may be suggestive of mu- tients undergoing hematological stem cell transplan- cormycosis but are rarely diagnostic because the ini- tation and patients with severe burn. 1, 4, 10, 32-40 Other tial imaging study is frequently negative or has subtle immunocompromised hosts, such as patients with findings. 11 Diagnosing mucormycosis almost always AIDS, rarely have been reported with this disease. requires histopathologic evidence of fungal invasion of the tissues. Culturing organisms from a potential Symptoms infected site is rarely sufficient to establish the diag- Infection is acquired through the respiratory tract. nosis of mucormycosis. The causative agent is ubiqui- In this text, only the infection occurring via the tous, may colonize a normal person, and is a relatively respiratory tract is discussed. Once the infection is frequent laboratory contamination. Additionally, the established in the paranasal sinuses, the infection can organism may be killed during tissue grinding, which easily spread to and enter the orbit via the nasolac- is routinely used to process tissue specimens for cul- rimal duct and medial orbit. 1 The ease of spread may ture, 1, 8, 11 thus a sterile culture does not rule out the be due to the thinness of the lamina papyracea and infection. Furthermore, waiting for the results of the perforation of the medial wall by arteries and veins. fungal culture may delay the institution of the appro- Spread to
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