Saudi Journal of Kidney Diseases and Transplantation

: 2013  |  Volume : 24  |  Issue : 4  |  Page : 768--772

Rhino-orbitocerebral mucormycosis in a patient with idiopathic crescentic glomerulonephritis

Suzan Sanavi1, Reza Afshar2, Siamak Afshin-Majd3,  
1 Parsa Hospital, Tehran, Iran
2 Department of Nephrology, Shahed University, Mustafa Khomeini Hospital, Tehran, Iran
3 Department of Neurology, Shahed University, Mustafa Khomeini Hospital, Tehran, Iran

Correspondence Address:
Suzan Sanavi
Parsa Hospital, Tehran


Mucormycosis, caused by mucorales, is an acute, rapidly progressive infection associated with high mortality. Rhino-orbitocerebral infection is the most common variant and is generally seen in association with immune deficiency syndromes. Prompt medical treatment of this infection and debridement decreases the mortality rate. We describe a 47-year-old man with crescentic glomerulonephritis on maintenance prednisolone therapy. He had earlier received steroid and cyclophosphamide pulse therapies. Renal functions improved following immunosuppressive treatment. In the third month of maintenance therapy, he presented to us with left-sided facial swelling and bloody nasal discharge. He had high blood sugar and acidic blood pH (ketoacidosis), probably due to steroid therapy. Magnetic resonance imaging of the head and sinuses showed inflammation and mass in the ethmoid sinus and nose with partial septal destruction, proptosis, global destruction of the left eye, brain infarction and carotid artery obliteration. Endoscopic biopsy of the sinuses revealed severe tissue necrosis. Samples of nasal discharge and biopsy tissue showed aseptate hyphae on light microscopy and culture, compatible with Rhizopus. The patient was treated with amphotericin B and multiple wound debridements along with ethmoidectomy and enucleation of the left eye. He was discharged in good general condition but with mild right hemiparesis. On follow-up examination at one year, there were no signs of fungal infection or renal dysfunction.

How to cite this article:
Sanavi S, Afshar R, Afshin-Majd S. Rhino-orbitocerebral mucormycosis in a patient with idiopathic crescentic glomerulonephritis.Saudi J Kidney Dis Transpl 2013;24:768-772

How to cite this URL:
Sanavi S, Afshar R, Afshin-Majd S. Rhino-orbitocerebral mucormycosis in a patient with idiopathic crescentic glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2021 Jun 16 ];24:768-772
Available from:

Full Text


Mucormycosis is a rare necrosant fungal infection due to Zygomycetes belonging to the Mucoraceae family, and is the second most common mould after Aspergillus in cultureproven invasive infections in patients with hematological malignancies and recipients of stem cell transplants. [1],[2] These fungi result in severe, rapidly progressive infection, particularly in immuno-compromised patients such as those with diabetes mellitus with uncontrolled blood sugar and patients with hematologic malignancies. Patients with extensive burn injuries, renal failure, prolonged use of corticosteroids and deferoxamine treatment have also been reported to develop mucormycosis. [3] Absidia, Mucor, Rhizomucor, Rhizopus (47% of isolates), Cunninghamella and Apophysomyces produce aggressive infections (the first four agents are the most common). [1] Apophysomyces elegans can infect individuals with a normal immune system as well. [3],[4] In rhino - rbitocerebral mucormycosis (ROCM), the respiratory system is the main route of entry of the pathogens; however, trauma plays a contributory role in some cases. [4] The spectrum of disease ranges from localized cutaneous lesions to disseminated disease. [5] The most common presentations of mucormycosis are ROCM followed by involvement of the respiratory system, abdomen and skin. [3] The current report describes a case of rapidly progressive rhinocerebral mucormycosis that occurred in a patient who had received a short course of corticosteroid therapy.

 Case Report

A 47-year-old male patient presented with a two-week history of dark urine and low-urine output associated with vomiting. Laboratory analysis revealed elevated blood urea nitrogen (BUN) and serum creatinine levels (150 and 9 mg/dL, respectively), while blood sugar and hemoglobin levels were normal. Urine sediment showed dysmorphic red blood cells (RBCs) and granular casts; however, the low urine volume made 24-h urinary protein measurement not feasible. Ultrasonography showed bilateral enlarged kidneys and cortical hyper-echogenicity. With a probable diagnosis of rapidly progressive glomerulonephritis (RPGN), supplementary laboratory tests including anti-double stranded DNA (dsDNA), anti-glomerular basement membrane (GBM) and anti-neutrophilic cytoplasmic antibodies (ANCA) were requested and a kidney biopsy was performed. The patient was started on hemodialysis (HD) and intravenous methylpred-nisolone pulse therapy (15 mg/kg for 3 days). The kidney biopsy specimen on light microscopy showed crescentic glomerulonephritis with 30% interstitial fibrosis. An immunofluorescence study of the specimen was normal. Intravenous cyclophosphamide pulse was administered once and oral prednisolone (60 mg/day) was continued. All serologic tests were negative and the patient was diagnosed to have idiopathic crescentic glomerulonephritis (GN). With the treatment given, the patient's serum creatinine decreased to 0.9 mg/dL and he was discharged after two weeks on oral prednisolone. During the next two months of follow-up, the oral prednisolone was tapered to 10 mg/day while the renal function and blood sugar remained normal. In the third month of maintenance steroid therapy, the patient presented with bloody nasal discharge of sudden onset associated with pain and swelling of the left upper hemi-facial area; there was no history of trauma or fever. The patient was afebrile on physical examination. He was found to have swelling of the left eye with redness, nasal ulcer with bloody discharge and right hemiparesis. Magnetic resonance imaging (MRI) of the head and sinuses showed inflammation of the ethmoid sinus, mass in the nasal septum, global destruction of the left eye, proptosis, left-sided hemispheric infarction and carotid artery obliteration [Figure 1] A and B. Laboratory investigations revealed high blood sugar of 500 mg/dL, 1 + urine ketone, arterial blood pH of 7.2 and serum creatinine of 1 mg/dL. The patient was started on treatment for diabetic ketoacidosis (DKA) and was scheduled for sinus endoscopy and biopsy. In view of the rapidly progressive necrosis, it was found that the nasal septum had undergone partial destruction within few hours. Debridement and tissue sampling for microscopic examination and culture were performed. Considering the high blood sugar, DKA and immunosuppression in the patient, high-dose empirical medical therapy was initiated for mucormycosis with amphotericin B (1 mg/kg/d) along with proper antimicrobial coverage including cefazolin, rifampin and metronidazole. Light microscopic observation of the nasal discharge and tissue showed aseptate hyphae compatible with mucorales [Figure 2]. As tissue necrosis was rapid and extensive, with severe eye involvement despite proper medical treatment and debridement, the patient underwent ethmoidectomy and enucleation. After 48 h, gray color Rhizopus colonies grew in culture. During the 35 days of hospitalization, the patient underwent several debridements until necrosis disappeared in pathologic reports. The renal function remained normal during hospital stay and prednisolone was discontinued. The patient was discharged in good general condition but with mild right hemiparesis. On follow-up examination at one year, there were no signs of fungal infection or renal dysfunction.{Figure 1}{Figure 2}


Fungal infections remain a significant cause of morbidity and mortality in patients with diabetes, malignancies and those that are immunocompromised. Infection with fungi such as Candida and Aspergillus is more common than mucorales. [1],[6] Fungi of the Mucoraceae family are saprophytes that can exist anywhere and are characterized by rapid growth, particularly in the presence of high glucose concentrations as well as warm and acidic environments. Rhizopus organisms have an enzyme, ketone reductase, which allows them to thrive in the presence of high glucose and acidic conditions. It has been shown that the growth of Rhizopus is enhanced in the serum of individuals with DKA, while serum from healthy individuals inhibits their growth. [2] The Zygomycetes are ubiquitous in nature, and can be found on decaying vegetation and in the soil. These fungi grow rapidly and release large numbers of spores that can become airborne. Because Zygomycetes are common in the environment, they are relatively frequent contaminants in the clinical microbiology laboratory; all humans have ample exposure to these fungi during day-to-day activities. The fact that Zygomycosis is a rare human infection reflects the effectiveness of the intact human immune system. This is further supported by the finding that almost all human infections due to a Zygomycete occur in the presence of some underlying immune compromising condition. They can invade vessels and produce severe disseminated diseases in susceptible patients. [2],[5] The present patient is one such predisposed subject because of steroid-induced hyperglycemia, DKA and use of immunosuppression with steroids and cyclophosphamide.

A history of RPGN accompanied by bloody nasal discharge may indicate another diagnosis, namely Wegener's granulomatosis. In our patient, absence of granulomas in the kidney and sinus biopsies, presence of wide aseptate hyphae and negative ANCA ruled out this diagnosis. Fortunately, despite the presence of multiple risk factors for poor outcome, including renal disease as well as metabolic acidosis and immunosuppression, the patient had a favorable outcome due probably to early diagnosis and treatment.

Mucormycosis is an acute rapidly progressive destructive disease, and the RCOM variant has an undesirable prognosis. Until the advent of amphotericin-B in the 1950's, mucormycosis was a universally fatal fungal infection. One case series by Ericsson et al reported that the survival rate is approximately 80% when both medical and surgical therapies are administered. [7] A small retrospective analysis by Strausser et al reported that the survival rate is about 48%. [8] The predictors of a poor survival include presence of renal disease, leukemia, hemiparesis or hemiplegia, bilateral sinus involvement and deferoxamine therapy. [9] In a study by Alleyne et al, the most important predictor of survival was the underlying disease. [9] Early diagnosis and intervention with amphotericin-B lipid complex and surgery directly correlated with patient survival. [10] The Mucoraceae family responds partially to pharmaceutical therapy. Therefore, high doses of amphotericin-B (1- 1.5 mg/kg/day) are recommended and the azoles preparations such as ketokonazole have no influence on these fungi. [10] Long-term intravenous drug therapy for mucormycosis is mandatory, which makes the treatment difficult and intolerable. Additionally, amphotericin-B is a nephrotoxic drug, which mandates careful monitoring of renal functions and serum potassium concentration. [11] Fortunately, despite the presence of previous RPGN and renal dysfunction in our patient, the renal function and serum potassium concentrations remained in the normal range, which indicates proper judicious administration of amphotericinB and careful monitoring. Early diagnosis and aggressive medical and surgical intervention were life saving in the patient.


1Sugar AM. Agents of mucormycosis and related species. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 5 th ed. New York: Churchill Livingstone; 2000. p. 2685-91.
2Khatiwada P, Giri A, Khatiwoda P. Mucormycosis in Diabetes Mellitus. J Adv Intern Med 2012;1:73-5.
3Pauls DR, Ravenel JG, Judson MA. A neutropenic patient with rapidly progressive lung lesion. Chest 2004;126:1364-7.
4Garcia-Covarrubias L, Bartlett R, Barratt D, Wassermann RJ. Rhino-orbitocerebral mucormycosis attributable to Apophysomyces elegans in an immunocompetent individual: Case report and review of the literature. J Trauma 2001;50:353-7.
5Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of Zygomycosis: A review of 929 reported cases. Clin Infect Dis 2005;41:634-53.
6Sanavi S, Afshar R, Gashti H. Fungal abdominal wall abscess in a renal transplant recipient. Saudi J Kidney Dis Transpl 2006;17: 383-5.
7Ericsson M, Anniko M, Gustafsson H, Hjalt CA, Stenling R, Tärnvik A. A case of chronic progressive rhinocerebral mucormycosis treated with liposomal amphotericin B and surgery. Clin Infect Dis 1993;16:585-6.
8Strausser MD, Kennedy RJ, Adam RD. Rhinocerebral mucormycosis. Therapy with amphotericin B lipid complex. Arch Intern Med 1996;156:337-40.
9Alleyne CH Jr, Vishteh AG, Spetzler RF, Detwiler PW. Long-term survival of a patient with invasive cranial base rhinocerebral mucormycosis treated with combined endovascular, surgical, and medical therapies: Case report. Neurosurgery 1999;45:1461-3.
10Sugar A. Agents of mucormycosis and related species, In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and practice of infectious diseases, 6 th ed., vol. 2. Philadelphia: Elsevier Churchill Livingstone; 2005. p. 2973-84.
11Bodhe PV, Kotwani RN, Kirodian BG, Kshirsagar NA, Pandya SK. Open label, randomized, comparative phase III safety and efficacy study with conventional amphotericin B and liposomal amphotericin B in patients with systemic fungal infections. J Assoc Physicians India 2002;50:662-70.