|Year : 2015 | Volume
| Issue : 1 | Page : 67-71
Zygomycosis of temporal bone in uncontrolled diabetes mellitus: A rare cause for skull base osteomyelitis
Sushil Kumar Aggarwal1, Preeti Agarwal2
1 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
2 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
|Date of Web Publication||8-Dec-2014|
Sushil Kumar Aggarwal
Assistant Professor, Department of ENT, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Zygomycosis is a serious and often rapidly fatal infection especially in immunocompromised patients. Rhinocerebral mucormycosis is the most common clinical form, accounting for about 50% of the reported cases. Impaired delivery of the antifungal drugs to the site of infection because of vascular thrombosis, and limited aggressive surgery because of the complex anatomy of the rhino-orbital region warns that early diagnosis and aggressive management is required in these patients. We encountered a rare case of zygomycosis of the temporal bone causing skull base osteomyelitis in a diabetic patient. The causative agent for skull base osteomyelitis has mainly been Pseudomonas aeruginosa, and rarely Aspergillus, but zygomycosis has not been mentioned as its cause in literature. Hence, we are reporting this case.
Keywords: Skull base osteomyelitis, temporal bone, zygomycosis
|How to cite this article:|
Aggarwal SK, Agarwal P. Zygomycosis of temporal bone in uncontrolled diabetes mellitus: A rare cause for skull base osteomyelitis. Muller J Med Sci Res 2015;6:67-71
|How to cite this URL:|
Aggarwal SK, Agarwal P. Zygomycosis of temporal bone in uncontrolled diabetes mellitus: A rare cause for skull base osteomyelitis. Muller J Med Sci Res [serial online] 2015 [cited 2020 Aug 10];6:67-71. Available from: http://www.mjmsr.net/text.asp?2015/6/1/67/146469
| Introduction|| |
The term 'Zygomycosis' refers to a group of rare infections caused by sparsely, septate filamentous, saprophytic fungi belonging to the class Zygomycetes and the order Mucorales. Zygomycosis is a serious and often rapidly fatal infection, especially in immunocompromised patients. The species of the genera Absidia, Rhizopus, Rhizomucor, Mucor, Apophysomyces, Saksenaea, Cunnighamella, Cokeromyces, and Syncephalastrum have been reported to cause invasive infections. However, the species of the genera Rhizopus, Absidia, and Rhizomucor are the most commonly reported pathogens. 
Mucormycosis is uncommon, but has become more prevalent due to the growing number of patients with metabolic or immunological imbalances.  It remains as a potentially lethal fungal infection, even though antifungal therapy and aggressive surgical intervention are currently available.  Rhinocerebral mucormycosis is the most common clinical form, accounting for about 50% of the reported cases, and the most fatal clinical category, compared to pulmonary, cutaneous, gastrointestinal, and disseminated mucormycosis.  Approximately 70% of the rhinocerebral cases are found in diabetic patients with ketoacidosis.  Besides diabetic ketoacidosis, chronic metabolic acidosis due to other causes, such as chronic renal failure with uremia, chronic salicylate poisoning, and methylmalonic aciduria, has also been reported as a risk factor for mucormycosis. Isolated central nervous system infection and invasive rhinocerebral mucormycosis in immunocompetent patients have also been reported. ,,
The survival rate is 82% for patients with isolated rhinomaxillary mucormycosis, whereas, the prognosis is markedly poor in cases of cerebral involvement, with a survival rate of 38-50%, despite aggressive surgery, antifungal therapy, and reversal of the underlying predisposing factors. , The reason being, mucormycosis causes angioinvasion, thrombosis, and tissue necrosis, which might result in the poor penetration of antifungal agents to the site of the infection.  Impaired deliveries of the antifungal drugs to the site of infection, because of vascular thrombosis, and limited aggressive surgery because of the complex anatomy of the rhino-orbital region, cautions for early diagnosis and aggressive management in these patients. We are reporting a rare case of zygomycosis of the temporal bone causing skull base osteomyelitis in a diabetic patient, which has not been reported as its cause in literature to date, to the best of our knowledge.
| Case Report|| |
A 50-year-old male presented to the Outpatient Department of our tertiary care institute with a chief complaint of right ear discharge for eight months and left facial deviation for around one month. The patient also complained of headache for the last three months. A history of nasal twang, hoarseness of voice, and cough during swallowing were also present for one month. On examination, many granulations were present at the bony-cartilaginous junction, with discharge over the tympanic membrane (TM). The left external auditory canal (EAC), left TM, and nose were normal on examination. In the oral cavity, the uvula was deviating to the left side with palsy on the right side. On indirect laryngoscopic examination, right vocal cord (VC) palsy was present. The eleventh and twelfth cranial nerves were normal on examination. The patient had a history of diabetes mellitus for the last 10 years, but for the last one year, his blood sugar levels were uncontrolled and he was put on insulin for the last three months. There was no history of hypertension or asthma, but the patient had undergone coronary artery bypass grafting (CABG) two years back.
Contrast-enhanced computed tomography (CECT) of the temporal bone was performed, which showed soft tissue density in the middle ear and EAC, with bony erosion of EAC. There was dehiscence of the facial canal in its vertical course. Enhancement was also present on computed tomography (CT) on the right side of the skull base, extending up to the petrous apex area. Magnetic resonance imaging (MRI) also showed mastoiditis on the right side, with hyperintensity seen in all sequences at the right skull base area.
The patient was taken up for biopsy under general anesthesia (GA). On examination under a microscope (EUM), there were many granulations and polyps present in the EAC. They were removed and sent for histopathological examination (HPE). The tympanomeatal flap was necrosed. In the middle ear, the incus and malleus were necrosed. The antrum was opened and the aditus and attic widened. There was hypertrophic mucosa and granulations present in the mastoid air cells and middle ear. They were removed and sent for HPE. The ridge was lowered and the bridge removed. The facial canal was dehiscent in its horizontal and vertical course and the facial nerve was edematous in its vertical course. The findings during surgery were suggestive of malignant otitis externa (skull base osteomyelitis), with the presence of a lot of necrotic blackish tissue, which was removed and sent for HPE. The HPE report showed mucormycosis of the left temporal bone, with microscopic findings of stratified squamous epithelium-lined tissue, with an underlying inflammatory granulation tissue, multinucleated giant cells, and fungal colonies displaying aseptate hyphae, with right angle branching. The fungus invaded the normal mucosa and bony tissues of the ear [Figure 1] and [Figure 2].
|Figure 1: Section shows irregular PAS positive non-septate acute angle branching fungal hyphae. (Periodic acid shiff ×20)|
Click here to view
|Figure 2: Fungal hyphae are positive for CSM (Colloid silver methanamine ×40)|
Click here to view
The patient was given intravenous liposomal amphotericin, up to 3.5 g, which he tolerated very well. Also, ear douching with acetic acid was done regularly and the slough was removed twice weekly. The patient had a dramatic relief of his symptoms of ear discharge and headache at the completion of the amphotericin therapy. The patient was discharged on oral voriconazole and he was advised to continue voriconazole for six months. The patient came for follow-up after completion of voriconazole treatment and his headache had subsided completely, with a dry right ear. The granulations in the right EAC had disappeared completely, with a normal looking EAC and right TM. Repeat magnetic resonance imaging (MRI) was performed, which showed only fibrosis at the right skull base area without any enhancement. The patient is on regular follow-up for the last one year without any fresh complaints, and with complete disappearance of the headache and ear discharge.
| Discussion|| |
Mucormycosis is a fungal infection that most often develops in individuals with immunologically compromising conditions.  Other factors predisposing to invasive mucormycosis include poorly-controlled diabetes mellitus, prolonged corticosteroid treatment, hematological malignancies, severe burns/trauma, chronic kidney disease, acquired immunodeficiency syndrome (AIDS), immunosuppressant use following solid organ transplant, and intravenous drug abuse. ,,, If diabetes mellitus is poorly controlled and the patient develops ketoacidosis, it becomes a high-risk factor, as it relates to cellular immune dysfunction. 
These pathogens are prone to invade and spread along the blood vessels, particularly the arteries. The fungus proliferates within the internal elastic lamina, dissecting it away from the media. As the hyphae penetrate the endothelium, thrombotic arteritis, infarction, hemorrhage, and extensive necrosis follow. 
Rhino-orbito-cerebral (ROC) mucormycosis is classically presented as a fulminant opportunistic infection in diabetic or immunocompromised patients. The primary route of rhino-orbital-cerebral mucormycosis is through direct extension from the nose and/or paranasal sinuses, delineating the organism's predilection for the nasal cavity and paranasal sinuses. The infection arising from the nasal area or paranasal sinuses may spread to the orbit or intracranially after destroying the adjacent bone and soft tissues. The pathological explanation for this invasive pattern is that the fungus has the propensity to grow along the walls of the blood vessels.  Mucormycosis may spread intracranially from the paranasal sinuses along the perivascular channels, or through the cribriform plate into the anterior cranial fossa. Clinically, they frequently present as fever, sinusitis, headache, periorbital or facial swelling, ptosis, visual loss, and ophthalmoplegia. Convulsion, changes in consciousness, coma, and stroke may occur. Cranial nerve palsies, proptosis, and epistaxis have also been reported. , A rare manifestation of mucormycosis originating in the paranasal sinuses includes extension along the sphenoid ridge into the middle ear, hematogenous dissemination to the lung or a more chronic and indolent course extending over many weeks.  The patients with a chronic course usually have a higher overall survival rate than those with the acute form. Factors associated with poor survival in ROC mucormycosis include delay in diagnosis and treatment, hemiparesis, bilateral sinus involvement, and facial necrosis. , Our patient also presented to us with zygomycosis of the temporal bone, which is a rare causative agent for skull base osteomyelitis.
The diagnosis is confirmed histologically by demonstrating tissue invasion and subsequent tissue reaction to the fungi, rather than just the presence of the organism.  Blood and tissue cultures, on the other hand, are used to identify the specific species. The microscopical examination of the tissue biopsy shows an acute and/or chronic inflammatory process, necrosis, and hyphal elements, also seen in our patient. The hyphae are characteristically broad and ribbon-like, with irregular branching at right angles, similar to our case. Cultures can be used to identify the specific species, although the cultures may fail to grow despite the presence of widespread and aggressive disease. 
Computed tomography (CT) findings of sinonasal mucormycosis include soft tissue opacification with hyperdense material, nodular mucosal thickening, and an absence of fluid levels in the maxillary, ethmoid, frontal, and sphenoid sinuses, in decreasing order of incidence. Other CT features include bony changes of the sinus wall, a focal mass with increased density in the sinus, and infiltration of the adjacent soft tissue or bone destruction.  The sinus contents have a variety of magnetic resonance (MR) signal characteristics, including T2 hyperintensity or marked hypointensity on all sequences, possibly due to the presence of iron and manganese in the fungal elements. In our patient also, MR showed hyperintensities in all the sequences at the right skull base region. For ROC mucormycosis, thickening and lateral displacement of the medial rectus muscle is characteristic of orbital invasion of the disease from the ethmoid sinuses. A lack of enhancement of the superior ophthalmic vein or ophthalmic artery and internal carotid artery may be seen, and this is related to vasculitis and thrombosis of these vessels. Intracranial findings include infarcts related to vascular thrombosis, mycotic emboli, and frontal lobe abscesses. 
In the past decade, the aggressive surgical debridement of the lesions was considered as the treatment of choice for rhino-orbital mucormycosis. Orbital exenteration was often indicated due to the rapid invasion and local extension to the orbits. With the advent of new therapeutic regimes, however, the treatment strategy now involves rapid diagnosis, reversal, and stabilization of the underlying medical conditions, systemic antifungals, and appropriate surgical debridement, only as needed.  Surgical procedures play a role in early diagnosis, and if required, repeated surgery should be done to treat the extensive disease.  The argument for radical debridement of all affected tissues in a patient with mucormycosis is based on the capacity of the fungus to spread along the walls and the lumen of the blood vessels, leading to necrotizing of the arteritis and ischemic necrosis of the involved tissues.  This results in poor penetration of the systemically administered drugs. Diabetic patients with ROC mucormycosis have the best chance of survival, as the underlying metabolic derangement is most amenable to treatment.  Patients with other immunocompromised states have a poor outcome. Patients with liver disease rarely develop mucormycosis.  Although the extent and timing of surgical debridement necessary to maximize the outcomes of mucormycosis have never been defined, a recent study supports the concept of an 'aggressive-conservative' approach, in which all necrotic material is removed, but the limits of surgical debridement are defined by the use of frozen sections intraoperatively, and when possible, the uninvolved structures are spared.  In our case, we also followed the same approach with debridement of all the necrotic tissues and the normal tissue was preserved.
Intravenous amphotericin B is the drug of choice for mucormycosis. Amphotericin B is the only antifungal that has been proven to be efficacious. It is administered parenterally at 1.0-1.5 mg/kg of body weight/day to a total dose of 2.5-4.0 g in the immunocompromised.  Conventional amphotericin B treatment is limited by its renal and systemic toxic effects in the form of renal failure, hypokalemia, hepatic impairment, fever, and chills. The lipid formulation of amphotericin B, such as, the amphotericin-B lipid complex, incorporates amphotericin B into the liposomes, which increases the efficacy of the drug by facilitating prolonged administration, and thus, enables a higher cumulative dose to be administered, without an increase in adverse effects. Our patient was also given liposomal amphotericin up to 3 g, as he was not tolerating the conventional amphotericin. However, it must be taken in account that amphotericin B does not readily penetrate the blood-brain barrier and might be ineffective in cerebral mucormycosis.  As there are no reliable antifungal agents, surgical debridement combined with antifungal therapy is inevitable in the treatment of cerebral mucormycosis.  New antifungal agents and a combination of the existing agents in the treatment of mucormycosis have been reviewed recently.  Posaconazole is a reasonable salvage option for patients with mucormycosis refractory to or intolerant to polyene therapy. , The available data are insufficient to support a significant role of primary treatment for mucormycosis, however, posaconazole is an option for the oral step-down therapy for patients who have responded to amphotericin B. The drug is also beneficial for the treatment and prevention of any relapse of the central nervous system mucormycosis. , Our patient was put on oral voriconazole as a step-down therapy, which is our routine protocol, and our patient responded very well with improvement in his pain and ear discharge. Posaconazole is a reasonable option, but our patients cannot afford this drug because of financial constraints.
| Conclusion|| |
Zygomycosis is a rare, but aggressive and potentially fatal infection in immunosuppressed patients, especially in diabetes mellitus. In the past, it has usually been fatal without aggressive surgical debridement. However, with the advent of newer formulations of proven drug regimes, such as, amphotericin B colloidal dispersion, voriconazole, posaconazole, and so on, a greater success rate can be achieved, while obviating the need for an extensive and potentially disfiguring surgical debridement. Rhinocerebral mucormycosis is the most common clinical form, accounting for about 50% of the reported cases and the most fatal clinical category. We have reported zygomycosis as a rare cause of skull base osteomyelitis here, which has not been mentioned previously as its cause, and hence, zygomycosis must be taken into consideration in future in any case of skull base osteomyelitis, especially in immunocompromised patients.
| References|| |
Rinaldi MG. Zygomycosis. Infect Dis Clin North Am 1989;3:19-41.
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.
Chakrabarti A, Das A, Sharma A, Panda N, Das S, Gupta KL, et al
. Ten years' experience in zygomycosis at a tertiary care centre in India. J Infect 2001;42:261-6.
Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.
Gupta KL, Radotra BD, Sakhuja V, Banerjee AK, Chugh KS. Mucormycosis in patients with renal failure. Ren Fail 1989;11:195-9.
Espinoza CG, Halkias DG. Pulmonary mucormycosis as a complication of chronic salicylate poisoning. Am J Clin Pathol 1983;80:508-11.
Lewis LL, Hawkins HK, Edwards MS. Disseminated mucormycosis in an infant with methylmalonicaciduria. Pediatr Infect Dis J 1990;9:851-4.
Weprin BE, Hall WA, Goodman J, Adams GL. Long-term survival in rhinocerebral mucormycosis. Case report. J Neurosurg 1998;88:570-5.
Harril WC, Stewart MG, Lee AG, Cernoch P. Chronic rhinocerebral mucormycosis. Laryngoscope 1996;106:1292-7.
Parfrey NA. Improved diagnosis and prognosis of mucormycosis. A clinicopathologic study of 33 cases. Medicine (Baltimore) 1986;65:113-23.
Momeni AK, Roberts CC, Chew FS. Imaging of chronic and exotic sinonasal disease: Review. AJR Am J Roentgenol 2007;189 (Suppl 6):S35-45.
Peterson KL, Wang M, Canalis RF, Abemayor E. Rhinocerebral mucormycosis: Evolution of the disease and treatment options. Laryngoscope 1997;107:855-62.
Abedi E, Sismanis A, Choi K, Pastore P. Twenty-five years' experience treating cerebro-rhino-orbital mucormycosis. Laryngoscope 1984;94:1060-2.
Reed C, Bryant R, Ibrahim AS, Edward J Jr, Filler SG, Goldberg R, et al
. Combination polyene-capsofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008;47:364-71.
Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J Jr, Ibrahim AS. Recent advances in the management of mucormycosis: From bench to bedside. Clin Infect Dis 2009;48:1743-51.
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.
[Figure 1], [Figure 2]