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Year : 2016  |  Volume : 5  |  Issue : 1  |  Page : 28-32

Rhinocerebral mucormycosis: Race against time for surgeons

1 Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital, Bengaluru, Karnataka, India
2 Department of Orthodontics and Dentofacial Orthopedics, Vokkaligara Sangha Dental College and Hospital, Bengaluru, Karnataka, India

Date of Web Publication13-Jan-2016

Correspondence Address:
Jasleen Kaur Handa
Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital, K.R. Road, V.V. Puram, Bengaluru - 560 004, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.173878

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Rhinocerebral mucormycosis is a rare, aggressive, and rapidly progressive life-threatening opportunistic infection affecting the immunocompromised patients. It manifests as facial swelling, cellulitis, nasal obstruction and discharge, large areas of tissue destruction and necrosis, orbital cellulitis, ptosis, proptosis, and vision loss in advanced cases. The pathognomonic feature of the disease is the presence of invasive mycelium in the tissues. A case series on four patients diagnosed with rhinocerebral mucormycosis is presented. Diabetic ketoacidosis was the common risk factor observed in all the three patients. It was concluded that early diagnosis and aggressive medical and surgical treatment are necessary for decreasing the high mortality rate of the infection.

Keywords: Amphotericin B, ketoacidosis, phycomycosis, rhinocerebral mucormycosis, zygomycosis

How to cite this article:
Rajkumar G C, Handa JK, Ashwin D P, Vennila N S. Rhinocerebral mucormycosis: Race against time for surgeons. Int J Health Allied Sci 2016;5:28-32

How to cite this URL:
Rajkumar G C, Handa JK, Ashwin D P, Vennila N S. Rhinocerebral mucormycosis: Race against time for surgeons. Int J Health Allied Sci [serial online] 2016 [cited 2023 Dec 8];5:28-32. Available from: https://www.ijhas.in/text.asp?2016/5/1/28/173878

  Introduction Top

Mucormycosis is a rare, opportunistic, invasive, and fulminant fungal infection caused by fungi belonging to the class Zygomycetes, order Mucorales, and family Mucoraceae.[1]

It is an aggressive and fatal disease which occurs primarily in immunocompromised people anguishing from diabetes, lymphoma, leukemia, myelodysplastic syndromes, prolonged corticosteroid therapies, renal failure, and severe burns. It involves rhinocerebral areas, lungs, gastrointestinal tract, skin, and less frequently other organs. Lesions typically appear as extensive areas of necrosis. Secondary infections are common, and the course of disease is generally impetuous. The survival rate of the patient ranges from 6% to 73%.[2]

Early diagnosis is elemental and so is medical therapy with intravenous antifungal agents. Aggressive surgical debridement and correction of impaired immunity are the treatment strategies for mucormycosis.

  Case Report Top

Four patients between the age group of 6 and 50 years reported to the institute between 2012 and 2014 [Table 1]. They were diagnosed clinically and histologically. Uncontrolled diabetes mellitus associated with ketoacidosis was the common risk factor observed in all the patients.
Table 1: Patients with rhinocerebral mucormycosis

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Fever, lethargy, pain mimicking sinusitis, facial swelling, toothache, and nasal discharge were common clinical signs and symptoms to all the patients [Figure 1]. Orbital cellulitis as a clinical manifestation was seen in two patients. However, one patient had orbital pus discharge along with vision loss of the affected eye [Figure 2].
Figure 1: Facial swelling and cellulitis

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Figure 2: Orbital cellulitis with discharge and loss of vision in the affected eye

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Intraoral examination revealed a black-colored necrotic patch [Figure 3] of 2 cm × 1 cm in left hard palate associated with a generalized toothache. In another patient, brown necrotic area extending from the left premaxilla until the last erupted molar (not crossing the midline) was seen.
Figure 3: Black-colored necrotic patch affecting the hard palate

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Radiographic examination to evaluate the extent of the lesion and amount of bone destruction was done using the computed tomography (CT) scans. All the patients had maxillary sinus involvement. In two of the patients, ethmoidal sinus, orbit, and anterior cranial base were also involved which indicated intracranial spread of the disease [Figure 4].
Figure 4: Involvement of maxillary sinus in mucormycosis

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Histological examination and fungal culture were used primarily in all the patients for arriving at the diagnosis. Potassium hydroxide (KOH) mount and lactophenol cotton blue stain for fungal organisms was used which revealed colonization by pauciseptate fungal organisms with the hyphae branching at 90° [Figure 5]a and [Figure 5]b. The histopathological findings rendered diagnosis of fungal infection of the division Zygomycetes compatible with mucormycosis.
Figure 5: (a) Potassium hydroxide mount revealed pauciseptate fungal organism with 90° angulation (b) fungal growth in lactophenol cotton blue stain

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The medical therapy consisted of intravenous administration of liposomal amphotericin B (AmB) at 5 mg/kg/day to all the patients. Due to the medical condition of the patients and delay in reporting to the institute, surgical treatment could not be rendered to two of the patients. Both the patients died due to intracranial spread of the infection. Nevertheless, early surgical intervention helped in increasing the survival rate of two patients [Figure 6]. Intravenous liposomal AmB (5 mg/kg/day) was administered to the patients postsurgery for 10 days following which, in patient no. 4, incisional biopsy from oropharynx region was send for histopathological examination. A negative report for fungal organisms revealed absence of fungal species. Posaconazole 400 mg twice daily is being administered as salvage therapy for these patients.
Figure 6: (a) Aggressive wound debridement along with left hemimaxillectomy, (b) left orbit exenteration procedure (c) 2 months postoperative healing

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A strict protocol is followed for the patients on an outpatient basis. The blood sugar levels for the patients are within normal limits with injectable insulin. Patient no. 3 failed to follow-up for subsequent visits due to unavoidable circumstances. Patient no. 4 continues to follow-up at a regular interval of every 15 days.

  Discussion Top

RM is a rare, devastating, opportunistic fungal infection that rarely affects healthy adults. It generally affects immunocompromised patients, 80% of whom are diabetic.[3] Diabetic ketoacidosis is one of the main risk factors facilitating the zygomycosis growth. Both decreased numbers of neutrophils and abnormal phagocytic cell function at the site of infection induced by diabetic ketoacidosis plays a role in the pathogenesis of mucormycosis during this condition. Acidosis disrupts the inhibitory activity of sera against fungal growth by interrupting the capacity of transferrin to bind iron from the fungal species, leading to a major defect in host defenses against Zygomycetes. Chemotactic defect of polymorphs and presence of acidic, hyperglycemic medium favors the growth of Zygomycetes species. This characteristic finding can be correlated with our study where all patients had a history of uncontrolled diabetes associated with ketoacidosis.

The clinical presentation at early stages of the disease is often not apparent. The main signs and symptoms observed are odontalgia, sinusitis, facial swelling and cellulitis, nasal obstruction, and nasal discharge. These findings were seen in three of the patients. Involvement of orbit is evident in advanced stages manifesting mainly as orbital cellulitis and discharge and in rare cases, blindness due to retinal artery thrombosis. Mortality rate among patients with orbital involvement is 33%.[4]

RM is evident on plain radiographs of sinuses and orbits demonstrating sinus mucosal thickening, opacification, and destruction of the sinus wall. The extent of disease is well-demonstrated on CT or magnetic resonance imaging (MRI). Due to monetary constraints, two patients with intracranial spread could not get MRI done.

Identification of the fungal species requires culture, morphologic evaluation using stains and genetic analysis. KOH mount is widely used for demonstration of fungus and fungal elements by microscopic examination. Sabourauds' dextrose agar, a conventional complex medium, is further used for culture which shows rapidly growing mycelial colonies. Variety of special fungal stains such as Grocott, Periodic Acid-Schiff, Calcofluor, Fungifluor, and Blankofluor are available which help in identification of the microorganism. These stains work on the principal of binding to the chitin and glucans of the fungal cell wall. Genetic analysis involves using molecular tools for the identification to the species level of a strain. DNA barcoding involving a DNA target and sequence database helps in accurate molecular identification of Zygomycetes strain.[5]

Early diagnosis and resolution of predisposing factors are the critical factors affecting the mortality rate of the disease. Both medical and surgical therapy goes hand in hand in treatment of the disease.

AmB is the gold standard for the treatment of mucormycosis. It is a fungistatic agent with the main drawback of nephrotoxicity. Three main lipid formulations, i.e., liposomal AmB (AmBisome), AmB colloidal dispersion, AmB lipid complex, have been introduced which enhance the intracellular delivery of the drug to phagocytes and fungi and decrease its renal delivery.[6],[7]

Posaconazole, a triazole, is considered as a second-line drug for treatment of mucormycosis. It has been effectively used in sequential therapy at a dosage of 400 mg twice daily after the administration of liposomal amphotericin, as achieving steady-state plasma concentrations of this drug takes approximately 1 week. Studies have shown this drug to be safe despite use varying from months to years.[8],[9]

Proinflammatory cytokines, such as interferon-γ and granulocyte macrophage colony-stimulating factor have been used as adjunctive immune therapy as it enhances the ability of granulocytes to damage the agents of mucormycosis.[10] However, the role of recombinant cytokines in the primary treatment of mucormycosis is not well-defined.

Surgical care is the mainstay of treatment for any form of zygomycosis. Early and aggressive surgical removal of all infected and devitalized tissue is considered the best approach without which zygomycosis almost always is fatal. Surgical treatment for mucormycosis is based on the general condition of the patient and response to the medical therapy. Early aggressive surgical intervention in two patients prevented the further spread of infection.

Hyperbaric oxygen therapy as an adjunct therapy in treatment of RM has been reported in literature. It benefits by increasing the oxygen supply to the vessels and tissue inhibiting the growth of fungus. Although no definitive evidence exists that this treatment can lower mortality, it has been used to ameliorate tissue hypoxia and lactic acidosis.[11],[12]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005;41:634-53.  Back to cited text no. 1
Marx R, Stern D, editors. Oral and Maxillofacial Pathology. 1st ed. Hanover Park (IL): Quintessence; 2003. p. 104-6.  Back to cited text no. 2
Paultauf A. Mycosis mucorina. Virchows Arch Pathol Anat 1885;102: 543.  Back to cited text no. 3
Islam MN, Cohen DM, Celestina LJ, Ojha J, Claudio R, Bhattacharyya IB, et al. Rhinocerebral zygomycosis: An increasingly frequent challenge: Update and favorable outcomes in two cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:28-34.  Back to cited text no. 4
Herbrecht R, Letscher-Bru V, Bowden RA, Kusne S, Anaissie EJ, Graybill JR, et al. Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 2001;20:460-6.  Back to cited text no. 5
Veerareddy PR, Vobalaboina V. Lipid-based formulations of amphotericin B. Drugs Today (Barc) 2004;40:133-45.  Back to cited text no. 6
Hamill RJ. Amphotericin B formulations: A comparative review of efficacy and toxicity. Drugs 2013;73:919-34.  Back to cited text no. 7
van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: A retrospective summary of 91 cases. Clin Infect Dis 2006;42:e61-5.  Back to cited text no. 8
Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 2006;50:126-33.  Back to cited text no. 9
Gil-Lamaignere C, Simitsopoulou M, Roilides E, Maloukou A, Winn RM, Walsh TJ. Interferon- gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important Zygomycetes. J Infect Dis 2005;191:1180-7.  Back to cited text no. 10
Alvernia JE, Patel RN, Cai DZ, Dang N, Anderson DW, Melgar M. A successful combined endovascular and surgical treatment of a cranial base mucormycosis with an associated internal carotid artery pseudoaneurysm. Neurosurgery 2009;65:733-40.  Back to cited text no. 11
Price JC, Stevens DL. Hyperbaric oxygen in the treatment of rhinocerebral mucormycosis. Laryngoscope 1980;90 (5 Pt 1):737-47.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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