Journal of Otology & RhinologyISSN: 2324-8785

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Case Report, J Otol Rhinol Vol: 4 Issue: 5

Invasive Rhinocerebral Mycosis: A report of three cases from India

Malhotra S*, Sharma S, Bhatia NJK and Hans C
Department of Microbiology, Dr. Ram Manohar Lohia Hospital and PGIMER, New Delhi, India
Corresponding author : Dr Shalini Malhotra
Department of Microbiology, PGIMER & Dr. RML Hospital, New Delhi- 110001
Tel: 9810778233
E-mail: [email protected]
Received: July 11, 2015 Accepted: September 03, 2015 Published: September 07, 2015
Citation: Malhotra S, Sharma S, Bhatia NJK, Hans C (2015) Invasive Rhinocerebral Mycosis: A report of three cases from India. J Otol Rhinol 4:5. doi:10.4172/2324-8785.1000246

Abstract

Rhinocerebral mycosis is a rapidly progressive fatal opportunistic infection and is increasingly being recognized these days. Aspergillosis and zygomycosis are predominantly responsible for rhinocerebral mycosis. Here we are presenting three cases of rhinocerebral mycosis- two cases of rhinocerebral mucormycosis and one case of rhinocerebral aspergillosis. Diagnosis is established presumptively from fungal culture of sinus or nasal material and tissue biopsy for histopathological examination. MRI brain was done in all the three cases which showed extension of disease in the cavernous sinus (case 1), orbit and peri-orbital region (case 2) and frontal lobe (case 3). Amphotericin B was initiated in all the cases, while surgical debridement was done in the 3rd case. However two out of three cases were succumbed to their illness after 10-12 days of admission, suggesting high mortality in such cases.

Keywords: Mycosis; Rhinocerebral; Amphotericin B

Keywords

Mycosis; Rhinocerebral; Amphotericin B

Introduction

Rhinocerebral mycosis is a rapidly progressive fatal opportunistic infection and is increasingly being recognized these days. This is mainly due to the increased awareness of clinicians, increasing immunocompromised state, the advances in imaging, and the availability of microbiological techniques to confirm the diagnosis [1]. The disease is primarily found in those who are immune compromised, but it may also manifest in immune competent persons. Rhinocerebral mycosis is most commonly caused by Aspergillus and Zygomycetes, however candida, Cryptococcus, histoplasma and other fungal infection can also involve brain [2]. Mode of infection is inhalation of spores, leading to localised infection in the nasal mucosa, later it extensively spread to neighbouring structures like brain and orbit via destruction of frontal sinus, transphenoid route or rhino-orbitocerebral route [3] or may spread through haematogenous metastases or may just involve the blood vessels or the meninges. In cerebral aspergillosis, secretion of various necrotizing factors with toxic and lytic activity towards neurons and glial cells is the known mechanism [4]. Rhinocerebral mycosis usually manifests as an acute sinus infection but it can lead to serious complications such as cavernous sinus thrombosis and vascular invasion if not diagnosed and treated at that level. Due to extensive involvement of blood vessels, infarction and necrosis of the affected organ eventually occurs [5]. Involvement of brain and orbit is fatal and requires early diagnosis and extensive treatment. Surgical debridement and antifungal therapy for long duration along with treatment of underlying predisposing factor is the mainstay of treatment [6]. Here we are presenting three cases of rhinocerebral mycosis two cases of rhinocerebral mucormycosis and one case of rhinocerebral aspergillosis, which were managed in our hospital and out of them two cases were fatal.

Review of Cases

A review of the three rhinocerebral mycosis cases is briefly discussed here. Out of the three cases, two were females and one male and their age ranged from 34 to 70 years. Two patients were diabetic and in one case there was no evidence of any co-morbid condition. Case 1 [67/M] presented with swelling and pain over the left side of the face, deviation of the angle of the mouth to right side and drooling of saliva from left angle of mouth along with high grade fever with chills and rigors and headache. Case 2 [70/F] presented with painless loss of vision & ptosis in the right eye due to orbital involvement and case 3 presented with features of space occupying lesion due to frontal lobe extension of nasal mass like headache, vomiting and altered sensorium. On local examination of nasal cavity, necrotic material was present in the nasal cavity in all the three cases. On MRI brain, in case 1 left cavernous sinus thrombosis was observed, in case 2 swelling and edema was observed in bilateral fronto-nasal orbital region and bilateral maxillo- facial region, while in case 3 lobulated mass lesion in the left basifrontal lobe with herniation and direct extension with sinuses and nasal cavity was seen. All the patients were having increased total leucocyte count while case 1 and 2 were having raised blood sugar levels and HbA1c. Rest of the investigations were normal in all the three cases. Microbiological diagnosis was made from the necrotic material derived from nasal cavity in all the three cases and was in accordance with histopathological findings. In two cases, broad aseptate hyaline hyphae and in one case, septate hyaline hyphae with acute angle branching were seen in direct examination of nasal tissue. Two cases were confirmed as zygomycetes (case 1: Mucor spp. and case 2: Rhizopus spp.) while one case was Aspergillus flavus on Sabouraud Dextrose agar. On histopathological examination, in two cases features of mucormycosis were seen while in case 3, aspergillosis was identified. All the patients were started on Amphotericin B after KOH mount interpretation. In case 3 [34/F] surgical lobectomy was also done. However two patients out of three (case 2 and 3) succumbed to their illness within 10-12 days of admission to the hospital. The clinical and investigation details of the patients are summarised in Table 1 and 2.
Table 1: Demographics, Clinical features and examination of rhinocerebral mycosis cases.
Table 2: Radiological diagnosis, laboratory findings and management of rhinocerebral mycosis cases.

Discussion

Fungal infections of the CNS are frequently encountered as opportunistic infections in patients, whose host defence mechanisms have been compromised due to disease or due to immunesuppression [7]. Various predisposing conditions for development of rhinocerebral mycosis are diabetic ketoacidosis, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns, protein energy malnutrition and AIDS. Aspergillus and zygomycetes are saprophytic and remain in decayed vegetation and soil [8]. Rhinocerebral involvement usually occurs in three stages. First, inhaled spores infect the paranasal sinuses and necrotic lesions develop in the nasal mucosa and hard palate followed by either direct spread of infection through ethmoid sinuses or orbital infection develops via haematogenous route and then infection invades the intracranial region. The spores invade the vascular structures and are multiplied in the elastic lamina of the arteries. Hyphae erode the endothelium of the vessel walls causing necrosis, thrombus and infarcts [9]. In this series, all the cases were having necrotic debris in the nasal cavity. Hence examination of nasal cavity is required whenever dealing with space occupying lesion in the brain or in patients presenting with focal neurological deficit. Diabetes mellitus is a common predisposing factor for this infection especially for mucorales. Diabetic ketoacidosis disrupts iron binding of transferrin, resulting in increased proportion of unbound iron which may promote growth of fungus and in such condition patients are more prone for infections due to decreased neutrophil chemotaxis and phagocytosis [10]. In this series, two cases that were diagnosed as having mucormycotina were having diabetes mellitus, while in the third case which was diagnosed as aspergillosis, no immuno-compromised condition was found. Third case was previously operated for nasal polyposis 5 years back in some private hospital and the recurrence was diagnosed with extensive spread in the central nervous system, finally patient succumbed to its illness. This suggests the regular follow-up of post-operative cases of fungal polyposis for early diagnosis of recurrence and further preventing extensive spread to brain and orbit and increase mortality.
Rhinocerebral mycosis is associated with high mortality inspite of aggressive therapy. due to the angioinvasive property of fungi, causing vascular occlusion and extensive tissue necrosis. Diagnosis is critical for early administration of antifungals because if the infection spreads beyond the nasal mucosa to central nervous system or orbit then surgical excision is required which is difficult due to complex anatomy of cerebral region. Angioinvasiveness leads to vascular occlusion thereby impairing delivery of antifungal drugs [11,12]. MRI of the brain and sinuses are useful for establishing extension of the disease into the orbit and cranial cavity. Diagnosis is established presumptively from fungal culture of sinus or nasal material and tissue biopsy for histopathological examination [6]. MRI brain was done in all the three cases which showed extension of disease in the cavernous sinus (case 1), orbit and peri-orbital region (case 2) and frontal lobe (case 3). KOH mount of material from nasal cavity in all the three cases showed fungal hyphae- broad aseptate hyphae (case 1 and 2) and branched septate hyphae (case 3) and the results were found in accordance with histopathological examination of biopsy from nasal cavity. Treatment of rhinocerebral mycosis should consist of prompt control of underlying predisposing condition, aggressive surgical debridment of involved tissue, and administration of parentenal amphotericin B. However amphotericin B is nephrotoxic and regular monitoring of renal functions is required. Instead of amphotericin B, liposomal amphotericin B is less toxic with better bioavailability, but is costly and hence its use is limited in developing countries [6]. Hyperbaric oxygen therapy is believed to improve neutrophilic killing by higher oxygen delivery and delaying the growth of fungal spores and mycelium [13]. Intravenous Amphotericin B was initiated in all our cases, while surgical debridement was done in the 3rd case and diabetes was controlled in cases 1 and 2. However, inspite of aggressive management in all the three cases, two were succumbed to their illness after 10-12 days of admission, suggesting high mortality in such cases.
Hence to conclude, rhinocerebral mycosis although is a rare entity, is associated with high mortality and hence should be kept in mind when handling cases with space occupying lesion or features of focal neurological deficit especially in patients with diabetes. Nasal examination in such cases clinches the diagnosis of fungal etiology and hence should be included in general examination of such patients. MRI brain helps in early diagnosis and also helps in assessing the extent of spread in the central nervous system. Simple microscopy can assist in prompt initiation of appropriate antifungal therapy (Figures 1 and 2). Hence MRI of the brain and microscopic examination is required to assess the need of surgical debridement along with appropriate antifungal therapy.
Figure 1: MRI brain (orbit) of case 2 showing Soft tissue swelling and edema in bilateral fronto-nasal orbital region and bilateral maxillo- facial region (right> left).
Figure 2: MRI brain of case 3 showing lobulated mass lesion in the left basifrontal region of brain.

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