Mucormycosis in a surgical defect masquerading as osteomyelitis: a case report and review of literature

Mucormycosis is a rare, highly lethal opportunistic fungal disease affecting immune compromised and diabetic patients. Mucormycosis is considered as the 3rd most common invasive mycosis after candidiasis and aspergillosis in debilitating patients. It is caused by the filamentous fungi of the class zygomycetes. The infection usually begins in the nose due to inhalation of fungal spores. This fatal fungal disease needs a prompt and early definitive diagnosis, aggressive surgical therapy and high dose anti-fungal therapy. Here, we present a case report of Mucormycosis in a 64 year elderly diabetic male patient who was previously operated for myiasis and also the extensive review of the literature of the mucormycosis.


Introduction
Mucormycosis, an emerging angio invasive fungal infection, is considered as one of the most rapidly progressing and lethal form, caused by ubiquitous filamentous fungi mucorales in humans which usually begins in the nose and para nasal sinuses [1]. It is an opportunistic infection that occurs in patients with immune compromised , debilitating individuals or patients suffering from diabetes mellitus [2,3]. Infection may be due to inhalation, ingestion or contamination of traumatized mucosa like ulcer or extraction socket by fungal spores [4]. It can be found in fruits, soil, dust, and manure and can be cultured from the nasal mucosa of normal persons, where it may not cause clinical signs of infection [5]. The organisms are aerobic, but can live two to five days in vitro.
Although infection usually occurs after inhalation through the nose or mouth, a skin laceration can also become an opening for mycotic entry [6].

Patient and observation
A 64 year old male patient, farmer by profession , reported to outpatient department of Oral Medicine , Diagnosis and Radiology with a chief complaint of pain and pus discharge in relation to the left upper back tooth region since 4 months .Past history revealed that patient was asymptomatic 4 months ago , later he developed pain and pus discharge which was slow in onset , localized , dull in nature , intermittent with no aggravating or relieving factors .
Further dialog history revealed that patient also experienced numbness on left side of the face since 2 months .Past medical history revealed that patient was hypertensive and diabetic since 5 and 4 years respectively and currently on medication. Past dental history and supportive investigations revealed that patient underwent check up 4 years ago at a ENT doctor where it was provisionally diagnosed as a case of Nasal myiasis , surgical debridement of the lesion was done and maggots were retrieved .
Plain and contrast computed tomography of brain revealed a sharply defined , mildly hyperdense space occuping lesion of 24 x 19 mm in left temporal region and effaced sulcal spaces which showed mild enhancement on contrast with mild hyperostosis with widening of diploic spaces of greater wing of sphenoid bones which was suggestive of a meningioma. Following which patient was admitted at a Private dental hospital, treatment protocol was informed to the patient and after obtaining informed consent from the patient, he

Discussion
Mucormycosis is a rare fungal infection seen in the immuno compromised previously referred to as zygomycosis [7]. This condition was first described by Paltauf in 1885 in human beings [8]. Though this fungus is ubiquitous in the environment (damp places such as soil, composting vegetation, and bread etc), our body is protected by the immune system and is therefore rare. Risk factors for the disease include diabetes mellitus, leukemia, blood dyscracias, immunesuppressive conditions such as Graft versus host diseases etc [9]. It may also manifest in immu¬no competent persons [10]. Its occurrence in diabetic patients can be attributed to that fact that low ph or the acidosis, hyperglycemic state. In these patients the phagocytic capacity of granulocytes is reduced, increasing the free ferric ions availability which favors growth of the fungus and enzyme ketoreductase of Rhizopus fungi utilizes the available ketone bodies. Mucorales are ferrophilic fungi. Acidosis reduces the binding of iron to transferrin; in turn, available free iron helps in proliferation of the Mucorales [11]. Mucormycosis generally progresses in three stages [9]. The first stage occurs after the inhalation of the fungal spores and invasion of the para¬nasal sinuses, resulting necrosis of the nasal mucosa, turbinates, or hard palate. The second stage is characterized by direct extension of the disease into the maxillary sinus. During the last stage, the infection spreads into the cribriform plate or the orbit [9].

Clinical presentation
Mucormycosis has various clinical presentations .Six variants have been described by Eisenberg et al namely rhinocerebral, pulmonary, gastrointestinal, cutaneous, nervous system and disseminated. among these , rhinocerebral is the most common type accounting for one -third to one half of the reported cases [12], which is further categorized into two forms, highly fatal form called the Rhino-Orbital variant affecting ophthalmic and internal carotid arteries and a less fatal and more common variant Rhino-Maxillary affecting spheno palatine and greater palatine arteries [13]. The Rhino cerebral variant is the most common form of mucormycosis in patients with diabetic ketoacidosis accounting for 70% of published cases [14].
Maxillary, frontal, ethmoidal and sphenoidal sinuses are the most frequent location and the mean age of patients was 38.8 years. This ubiquitous fungus is angioinvasive resulting in thrombosis and ischemic tissue necrosis. A black necrotic eschar is the most characteristic and the pathognomic lesion. Patients usually present with malaise, headache, facial pain, swelling and low grade fever [6]. Necrosis of the maxilla is usually rare due to its rich vascularity .  [19]. Mostly patients with early case of mucormycosis may show normal CT and MRI study. Fungus is identified by hematoxylin and eosin stain , cultural sensitivity of the specimen and can confirm by Grocott's silver methenamine special staining technique which show the organism in vessel walls [21]. However, a polymerase chain reaction technique helps in identifying specific pathogenic strain and further treatment protocol.

Histopathological picture
Histopathological picture shows the characteristic ribbon like branching, smaller width non septate hyphae which are prominent and long , acute angled [17]. Hyphae are better visualized with PAS or silver strains. As the fungus is angio invasive it is commonly found in close proximity with the necrotic vessel walls. Usually tissue shows non-specific inflammatory cell infiltrate, with necrosis and granulation tissue along with the hyphae.

Management
Early diagnosis, prompt management (aggressive surgical intervention, concurrent anti fungal therapy and supportive measures such as hyperbaric oxygen therapy) is critical because of the invasive and fulminate course of the disease and has decreased the mortality rates drastically from 84% to 40 in a span of 40 years

Role of hyperbaric oxygen therap
Hyperbaric oxygen shows anti fungal activity by inhibiting lactic acidosis, enhanced phagocytosis and increased activity of polymorphonuclear leukocytes. It also contributes healing by increasing the oxygen tension to the hypoxic areas [27,28]. When the infection spreads intracranially and shows poor response to conventional treatments Iron-chelating agents like Deferasirox can Page number not for citation purposes 5 be administered although with varying results [22]. After obtaining negative cultures from the lesion , usually the surgical defect is closed with an obturator to prevent nasal regurgitation and improvement of aesthetics.

Competing interests
The author declares no competing interests.

Authors' contributions
Author Nishanth Gollamudi wrote the first draft of the manuscript.