Year : 2006 | Volume
: 17 | Issue : 3 | Page : 139--42
Mucormycosis presenting as palatal perforation.
S Jayachandran, C Krithika
Department of Oral Medicine and Radiology, Tamilnadu Govt Dental College and Hospital, Chennai, India
Department of Oral Medicine and Radiology, Tamilnadu Govt Dental College and Hospital, Chennai
Mucormycosis is an opportunistic fungal infection that is caused by normally saprobic organism of the class Zygomycetes. The main form of mucormycosis are pulmonary and rhinocerebral. Rhinocerebral mycormycosis typically starts in the maxillary antrum, particularly in poorly controlled diabetics. Invasion of surrounding tissue can cause necrotizing ulceration of palate with a blackish slough and exposure of bone. A case of mucormycosis presenting as palatal performation is discussed in this article.
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Jayachandran S, Krithika C. Mucormycosis presenting as palatal perforation. Indian J Dent Res 2006;17:139-42
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Jayachandran S, Krithika C. Mucormycosis presenting as palatal perforation. Indian J Dent Res [serial online] 2006 [cited 2016 May 4 ];17:139-42
Available from: http://www.ijdr.in/text.asp?2006/17/3/139/29873
Fungal pathogens are subdivided into those that remain superficial (i.e restricted to the epithelial surface) and those that invade deep organs and tissues (deep fungi). Most important by some species are considered opportunistic (infecting only immuno compromised hosts) and others truly pathogenic (i.e capable of infecting normal persons). Mucormycosis is an opportunistic deep fungal infection caused by "bread mold fungi" of the genera Mucor, Absidia, Rhizopus and Cunninghamella, also collectively known as Phycomycetes .
A 48-year-old male patient reported to the Department of Oral Medicine and Radiology, Tamil Nadu Government Dental College and Hospital, with the complaint of nasal regurgitation of food, associated with a purulent discharge from the nasal cavity and left lower eyelid for the past 15 days. History revealed that he had his left upper tooth extracted 1 month back, following which he noticed a small painless hole in the palate. He also gave a history of fever for the previous 10 days. There was no history suggestive of visual disturbances or altered mental status.
Past medical history revealed the patient to be a diabetic with a history of poor drug compliance. He had not been on any antidiabeticmedication over the previous two years.
General examination revealed the patient to be febrile with mild tachycardia and inflammatory submandibular lymphadenitis. Extra oral findings included right sided periorbital eel lulitis and ectropion of the left lower eyelid with an infra orbital sinus. A purulent discharge was seen from the sinus [Figure 1].
Intraorally, a 3x3 cm' circular perforation was noticed in the anterior region of the hard palate [Figure 2]. A blackish, necrotic, hemorrhagic mass was seen through the perforation. Based on the history and clinical presentation, a provisional diagnosis of a deep fungal infection was made.
Occlusal radiograph ofthemaxillashowedanilldefined radiolucent area in the anterior region of the hard palate [Figure 3]. CT sections [Figures 4, 5 and 6] demonstrated a lesion of soft tissue density in the nasal cavity, causing destruction of the nasal septum centrally, destruction of the medial walls of the antra bilaterally and perforation of the palate inferiorly. Partial destruction of the floor of the orbit and ethmoidal sinus could be seen on the coronal CT images. CT scan of the brain was apparently normal. Haemogram showed polymorphonuclear leucocytosis [Pa, L12E] and elevated ESR [36 mm/lhr]. Biochemical investigations revealed alarmingly high blood glucose of 426 mg/dl, associated with glycosuria and ketonuria. ENT, ophthalmologic and neurosurgical consults concurred with the diagnosis of rhinocerebral mucormycosis, secondary to diabetic ketoacidosis. Emergency medical management of diabetic ketoacidosis resulted in optimal glycaemic control, following which an incisional biopsy of the lesion was accomplished. The tissue was sent for histopathological examination, as well as fungal culture and sensitivity. Histopathological examination [Figure 6] showed broad, non-septate hyphae with acute right angle branchings suggestive of Mucor species. Although fungal culture showed no growth, a final diagnosis ofmucormycosis was made since cultures are frequently negative in a majority of cases, caused by Mucor species.
The patient was started on intravenous amphotericin B 60mg in 4 divided doses, cefotaxime lg bd and metronidazole 500mg tds. He was monitored closely for signs of amphotericin induced nephrotoxicity. Fortunately, his recovery was uneventful. Surgical debridement of the necrotic tissues was done under general anesthesia and a temporary palatal obturator was given. The patient is planned to be taken up for definitive palatoplasty after 6 months.
Organisms of the class Zygomycetes or Phycomycetes were first noted to cause disease in humans since 1800. Platauf is credited with the first description of Zygomycosis in his paper entitled. 'Mycosis mucorina' . The class 'Zygomycetes' is subdivided into two orders, which contain the agents of human Zygomycosis, the Mucorales and the Entomophthorales. Among the Mucorales, Rhizopus (most common), Mucor, Absidia, Rhizomucor, Cunninghamella, Saksenaea, Cokeromyces and Apophysomyces  have been implicated in causing human disease . The hallmarks of disease with these organisms are angioinvasion, thrombosis, infarction and necrosis of the involved tissue.
Mucorales are considered to be opportunistic pathogens that require a break down in host immune defenses, particularly disease processes that lead to neutropenia or neutrophil dysfunction .
The predisposing factors for mucormycosis are as follows:
1. Diabetes is the single most common predisposing factor especially when associated with ketoacidosis. Mucor thrives in an acid pH and glucoserich medium. Hyperglycemia enhances fungal growth and impairs neutrophil chemotaxis,while lactic acidosis decreases phagocytosis,.
2. Hematological malignancies (Leukemia , Lymphoma)
3. Solidorgan or Bone marrow transplants
5. Deferroxamine therpay  (Rhizopus species prefersaniron rich environment)
6. Severe and prolonged neutropenia
7. DeficientT Cell immunity
8. Immaturity andlow birthweight .
Zygomycosis presents as a spectrurn of diseases, depending on the portal of entry and the predisposing risk factors of the patient. The 5 major clinical forms are as follows :
3. Abdominal pelvic and gastrointestinal
4. Prunary cutaneous and
Rhinocerebral mucormycosis represents one-third to onehalf of all cases of zygomycosis . It manifests itself in a setting of poorly controlled diabetes in about 70% of the cases . The process originates in the paranasal sinuses following inhalation of the fungal spores. Disease begins with symptoms consistent with sinusitis-sinus pain, nasal discharge and soft tissue swelling . Then, it becomes rapidly progressive, extending into neighbouring tissues. Involved tissues become red, then violaceous and finally black as vessels are thrombosed and tissues undergo necrosis. Extension into the orbital region can lead to perimbital oedema, proptosis, tearing and ocular or optic nerve involvement . Spread along the cribriform plate can result in intracranial involvement.
The most common oral sign of mucormycosis is ulceration of the palate, which results from necrosis due to invasion of a palatal vessel . Extension from the sinuses into the mouth causes painful, black necrotic ulcerations in the hard palate . The lesion is characteristically large and deep, causing denudation of the underlying bone . Ulcers from mucormycosis have also been reported on the gingiva, lip and alveolar ridge.
Differential diagnosis of a lesion presenting as palatal perforation should include tertiary syphilis , leprosy, tantrum oris, mechanical trauma, intranasal cocaine abuse , malignancies, especially nasal T cell lymphomas, Wegener's granulumatosis and midline non-healing granuloma . But, evidence of diabetes or immunosuppression in a patient presenting with necrotic lesions of the nasal cavity and palate strongly favours the diagnosis of a deep fungal infection.
Plain radiographs of sinuses and orbits may demonstrate sinus mucosal thickening, with or without air-fluid levels, but this is not specific. CT scan with contrast or MRI may demonstrate erosion or destruction of bone or sinuses and help delineate the extent ofthe disease .
Key features associated with zygomycetes on direct examination of cytologic specimens is the presence of wide, ribbon like aseptate, hyaline, hyphal elements, often in the setting of extensive necrotic debris. The special stains used for this purpose include calcofluor white stain; Gomori methenamine silver stain (GMS), periodic acid schiff (PAS) and Papanicolai stains .
Diagnosis of zygomycosis is easily made on tissue sections. Involved tissue demonstrates focal areas of infection, necrosis and haemorrhage. Demonstration of aseptate hyphae with wide angle branching (45°sub to 90°sub ) with angioinvasion is characteristic ofMucor species .
Fungal selective media are used to suppress the growth of bacterial elements (inhibitory mold agar) but, results are frequently negative, despite positive histopathology. In fact fungal cultures are positive in only 15-25% of the cases . As the disease progresses with alarming rapidity, prompt and aggressive therapy is essential . Treatment of Zygomycosis requires several simultaneous approaches:
1. Surgical debridement
2. Antifungal therapy
3. Medical management or correction of the underlying Condition that predisposes the patient to the disease. Amphotericin B is the first line drug of choice for most cases of zygomycosis ,,, but its use may be associated with adverse effects such as nephrodoxicity (30-50%) that may prevent maintenance of effective doses andhence, monitoring serum creatinine, potassium, magnesium levels and blood urea nitrogen (BUN) is very important. Recently, liposomal amphotericin B (where the drug has been inserted into liposomes) is claimed to produce lesser nephrodoxicity, even at higher doses . Fluconazole may be of benefit in treating Zygomycetes infection,  although some reports indicate an increase in resistant organisms to fluconazole . Hyperbaric oxygen therapy is believed to improve neutrophilic killing by higher oxygen delivery and delaying or totally inhibiting the growth of fungal spores and mycelium .
Correction of the underlying diabetic ketoacidosis, improving neutropenia either with granulocyte infusions or by enhancing endogenous neutrophil production with growth factors  and discontinuation of iron chelation therapy orcorticosteroids is oftenwarranted.
Prognosis depends on several factors such as infection site, rapidity of diagnosis, type and severity of immunosupression and the like. The mortality rates were nearly 85% in earlier days; however after the introduction of combined therapy, more than 80% of the patients can be expected to survive . Hope for cure, however lies in early recognition and aggressive treatment.
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