Sections

Presentation

History

Symptoms of rhinocerebral mucormycosis are often nonspecific, complicating early diagnosis. The most common presentation includes facial pain, headache, lethargy, visual loss, proptosis, and/or palatal ulcer. Perinasal cellulitis and paresthesia are also common early clinical signs of rhinocerebral mucormycosis. The incubation period is measured in days. The clinical course can progress from normal to symptomatic in a week and from sinus opacification to uncal herniation and death in just a few days.^{[19, 20, 21, 22]}

General symptoms of rhinocerebral mucormycosis include the following:

Headache
Nausea
Fever
Lethargy

Facial symptoms of the disease include the following:

Weakness
Numbness
Pain

Nasal symptoms of rhinocerebral mucormycosis include:

Purulent drainage
Stuffiness and rhinorrhea
Epistaxis
Nasal hypoesthesia

Ocular symptoms include the following:

Periorbital or retro-orbital pain
Diplopia and blurred vision
Amaurosis (unilateral or bilateral)
Possible rapid progress to blindness

CNS symptoms include the following:

Convulsions
Altered mental status
Dizziness
Unsteady gait

Physical Examination

Many individuals with rhinocerebral mucormycosis have underlying diabetes mellitus, usually with acidosis and poor glycemic control. Patients with diabetic ketoacidosis accompanied by mental status changes should improve within 24-48 hours of treatment; if they do not, consider CNS pathology.

Nasal and palatal findings of rhinocerebral mucormycosis include the following:

Gray or erythematous appearance
Can progress to black necrotic masses (ie, black eschar)
Inflammation

Ocular findings include the following:

Orbital invasion
Orbital cellulitis
Conjunctival chemosis
Proptosis and periorbital edema
Ophthalmoplegia
Fixed pupil
Orbital apex syndrome^[23]
Blindness
Nystagmus
Visual loss secondary to retinal artery thrombosis or direct fungal invasion

Neurologic findings include the following:

Palsies of cranial nerves II, III, IV, V, VI, and VII - Commonly observed, prompting a thorough neurologic workup.
Cerebral edema and vascular compromise - May lead to coma and stroke

Differential Diagnoses

Gilbard SM, Della Rocca RC. Smith's Ophthalmic Plastic and Reconstructive Surgery. Nesi FA, et al, eds. Paranasal sinus disease and the orbit. 2nd ed. 1998. 896-930.
Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012 Feb. 54 Suppl 1:S23-34. [QxMD MEDLINE Link].
Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep. 2012 Aug. 14(4):423-34. [QxMD MEDLINE Link].
McLean FM, Ginsberg LE, Stanton CA. Perineural spread of rhinocerebral mucormycosis. AJNR Am J Neuroradiol. 1996 Jan. 17(1):114-6. [QxMD MEDLINE Link].
Margo CE, Linden C, Strickland-Marmol LB, Denietolis AL, McCaffrey JC, Kirk N. Rhinocerebral mucormycosis with perineural spread. Ophthal Plast Reconstr Surg. 2007 Jul-Aug. 23(4):326-7. [QxMD MEDLINE Link].
Anaissie EJ, Shikhani AH. Rhinocerebral mucormycosis with internal carotid occlusion: report of two cases and review of the literature. Laryngoscope. 1985 Sep. 95(9 Pt 1):1107-13. [QxMD MEDLINE Link].
Delbrouck C, Jacobs F, Fernandez Aguilar S. Carotid artery occlusion due to fulminant rhinocerebral mucormycosis. Acta Otorhinolaryngol Belg. 2004. 58(2):135-40. [QxMD MEDLINE Link].
Shah PD, Peters KR, Reuman PD. Recovery from rhinocerebral mucormycosis with carotid artery occlusion: a pediatric case and review of the literature. Pediatr Infect Dis J. 1997 Jan. 16(1):68-71. [QxMD MEDLINE Link].
Sheth SM, Talwalkar NC, Desai AP. Rhinocerebral mucormycosis in a case of renal failure. J Postgrad Med. 1981 Jul. 27(3):190b-193. [QxMD MEDLINE Link].
Stern LE, Kagan RJ. Rhinocerebral mucormycosis in patients with burns: case report and review of the literature. J Burn Care Rehabil. 1999 Jul-0Aug. 20(4):303-6. [QxMD MEDLINE Link].
Webb M, Dowdy L, Bundschu C. Cerebral mucormycosis after liver transplantation: a case report. Clin Transplant. 1998 Dec. 12(6):596-9. [QxMD MEDLINE Link].
Apaydin S, Ataman R, Cansiz H. Rhinocerebral mucormycosis in a kidney transplant recipient. Nephron. 1998. 79(1):117-8. [QxMD MEDLINE Link].
Maertens J, Demuynck H, Verbeken EK. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant. 1999 Aug. 24(3):307-12. [QxMD MEDLINE Link].
Penalver FJ, Romero R, Fores R. Rhinocerebral mucormycosis following donor leukocyte infusion: successful treatment with liposomal amphotericin B and surgical debridement. Bone Marrow Transplant. 1998 Oct. 22(8):817-8. [QxMD MEDLINE Link].
Salinas-Lara C, Rembao-Bojórquez D, de la Cruz E, Márquez C, Portocarrero L, Tena-Suck ML. Pituitary apoplexy due to mucormycosis infection in a patient with an ACTH producing pulmonary tumor. J Clin Neurosci. 2008 Jan. 15(1):67-70. [QxMD MEDLINE Link].
Dhiwakar M, Thakar A, Bahadur S. Improving outcomes in rhinocerebral mucormycosis--early diagnostic pointers and prognostic factors. J Laryngol Otol. 2003 Nov. 117(11):861-5. [QxMD MEDLINE Link].
Fairley C, Sullivan TJ, Bartley P, Allworth T, Lewandowski R. Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient. Ophthalmology. 2000 Mar. 107(3):555-8. [QxMD MEDLINE Link].
Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 1994 Jul-Aug. 39(1):3-22. [QxMD MEDLINE Link].
Guevara N, Roy D, Dutruc-Rosset C, Santini J, Hofman P, Castillo L. Mucormycosis--early diagnosis and treatment. Rev Laryngol Otol Rhinol (Bord). 2004. 125(2):127-31. [QxMD MEDLINE Link].
Turunc T, Demiroglu YZ, Aliskan H, Colakoglu S, Arslan H. Eleven cases of mucormycosis with atypical clinical manifestations in diabetic patients. Diabetes Res Clin Pract. 2008 Nov. 82(2):203-8. [QxMD MEDLINE Link].
Nithyanandam S, Jacob MS, Battu RR, Thomas RK, Correa MA, D'Souza O. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol. 2003 Sep. 51(3):231-6. [QxMD MEDLINE Link].
Bhansali A, Sharma A, Kashyap A, Gupta A, Dash RJ. Mucor endophthalmitis. Acta Ophthalmol Scand. 2001 Feb. 79(1):88-90. [QxMD MEDLINE Link].
Balch K, Phillips PH, Newman NJ. Painless orbital apex syndrome from mucormycosis. J Neuroophthalmol. 1997 Sep. 17(3):178-82. [QxMD MEDLINE Link].
Bengel D, Susa M, Schreiber H, Ludolph AC, Tumani H. Early diagnosis of rhinocerebral mucormycosis by cerebrospinal fluid analysis and determination of 16s rRNA gene sequence. Eur J Neurol. 2007 Sep. 14(9):1067-70. [QxMD MEDLINE Link].
Deshpande AH, Munshi MM. Rhinocerebral mucormycosis diagnosis by aspiration cytology. Diagn Cytopathol. 2000 Aug. 23(2):97-100. [QxMD MEDLINE Link].
Nair M, Kapila K, Verma K. Fine-needle aspiration: another diagnostic modality for rhinocerebral mucormycosis. Diagn Cytopathol. 1999 Oct. 21(4):300-1. [QxMD MEDLINE Link].
Gonzalez CE, Couriel DR, Walsh TJ. Disseminated zygomycosis in a neutropenic patient: successful treatment with amphotericin B lipid complex and granulocyte colony-stimulating factor. Clin Infect Dis. 1997 Feb. 24(2):192-6. [QxMD MEDLINE Link].
Luna JD, Ponssa XS, Rodríguez SD, Luna NC, Juárez CP. Intraconal amphotericin B for the treatment of rhino-orbital mucormycosis. Ophthalmic Surg Lasers. 1996 Aug. 27(8):706-8. [QxMD MEDLINE Link].
Seiff SR, Choo PH, Carter SR. Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthal Plast Reconstr Surg. 1999 Jan. 15(1):28-31. [QxMD MEDLINE Link].
Strasser MD, Kennedy RJ, Adam RD. Rhinocerebral mucormycosis. Therapy with amphotericin B lipid complex. Arch Intern Med. 1996 Feb 12. 156(3):337-9. [QxMD MEDLINE Link].
Reed C, Bryant R, Ibrahim AS, Edwards J Jr, Filler SG, Goldberg R, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008 Aug 1. 47(3):364-71. [QxMD MEDLINE Link]. [Full Text].
Garner D, Machin K. Investigation and management of an outbreak of mucormycosis in a paediatric oncology unit. J Hosp Infect. 2008 Sep. 70(1):53-9. [QxMD MEDLINE Link].
Tarani L, Costantino F, Notheis G, Wintergerst U, Venditti M, Di Biasi C, et al. Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girl. Pediatr Diabetes. 2009 Jun. 10(4):289-93. [QxMD MEDLINE Link].
Kulendra K, Habibi M, Butler C, Clarke P, Howard D. Use of posaconazole in the treatment of infective rhinocerebral mucormycosis. J Laryngol Otol. 2010 Dec. 124(12):1314-7. [QxMD MEDLINE Link].
Ervens J, Ghannoum M, Graf B, Schwartz S. Successful isavuconazole salvage therapy in a patient with invasive mucormycosis. Infection. 2014 Apr. 42(2):429-32. [QxMD MEDLINE Link].
Kazak E, Aslan E, Akalin H, Saraydaroglu O, Hakyemez B, Erisen L, et al. A mucormycosis case treated with a combination of caspofungin and amphotericin B. J Mycol Med. 2013 Sep. 23(3):179-84. [QxMD MEDLINE Link].
Hargrove RN, Wesley RE, Klippenstein KA, Fleming JC, Haik BG. Indications for orbital exenteration in mucormycosis. Ophthal Plast Reconstr Surg. 2006 Jul-Aug. 22(4):286-91. [QxMD MEDLINE Link].
Pelton RW, Peterson EA, Patel BC, Davis K. Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities. Ophthal Plast Reconstr Surg. 2001 Jan. 17(1):62-6. [QxMD MEDLINE Link].
Croce A, Moretti A, D'Agostino L, Zingariello P. Orbital exenteration in elderly patients: personal experience. Acta Otorhinolaryngol Ital. 2008 Aug. 28(4):193-9. [QxMD MEDLINE Link]. [Full Text].
Avet PP, Kline LB, Sillers MJ. Endoscopic sinus surgery in the management of mucormycosis. J Neuroophthalmol. 1999 Mar. 19(1):56-61. [QxMD MEDLINE Link].
Lari AR, Kanjoor JR, Vulvoda M, Katchy KC, Khan ZU. Orbital reconstruction following sino-nasal mucormycosis. Br J Plast Surg. 2002 Jan. 55(1):72-5. [QxMD MEDLINE Link].
Bullock JD, Warwar RE. Three patients with presumed rhino-orbital-cerebral mucormycosis. J Neuroophthalmol. 1999 Jun. 19(2):120-1. [QxMD MEDLINE Link].
Dhiman R, Arora V, Kotwal N. Rehabilitation of a rhinocerebral mucormycosis patient. J Indian Prostheodont Soc. 2007. 7:88-91.
Adler DE, Milhorat TH, Miller JI. Treatment of rhinocerebral mucormycosis with intravenous interstitial, and cerebrospinal fluid administration of amphotericin B: case report. Neurosurgery. 1998 Mar. 42(3):644-8; discussion 648-9. [QxMD MEDLINE Link].
National Institutes of Health. Isavuconazole in the treatment of renally impaired aspergillosis and rare fungi. NLM identifier: NCT00634049. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT00634049. Accessed: April 2, 2015.

Media Gallery

Clinical view of the face of a patient with rhinocerebral mucormycosis. Notice the cutaneous hemorrhagic ulcer on the right anterior cheek resulting from perforation of the fungus through the sinus cavity.
A cotton blue preparation of Rhizopus species.
A tissue hematoxylin and eosin stain of Rhizopus species.
The appearance of a culture slant of Rhizopus species.
Culture plates of Rhizopus species.
Low-power photomicrograph of a Gomori methenamine silver stain of Rhizopus species.
High-power photomicrograph of a Gomori methenamine silver stain of Rhizopus species.
CT brain scan illustrating the appearance of cavernous sinus thrombosis.
CT brain scan showing the appearance of a cerebral infarct.
CT scan of a patient who is suspected of having mucormycosis shows extensive involvement of the right orbit and adjacent sinuses.
This diabetic patient with mucormycosis presented with complete ophthalmoplegia and proptosis. Note the complete ptosis and periorbital edema on the right side.
Characteristic appearance of mucormycosis under the microscope.

of 12

Author

William P Baugh, MD Assistant Clinical Professor of Dermatology, Western University of Health Sciences; Medical Director, Full Spectrum Dermatology; Consulting Staff, Department of Dermatology, St Jude Medical Center

William P Baugh, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Laser Medicine and Surgery, Christian Medical and Dental Associations

Disclosure: Nothing to disclose.

Coauthor(s)

Cynthia C Lazzaro, DO Physician

Cynthia C Lazzaro, DO is a member of the following medical societies: American Academy of Dermatology, American Osteopathic College of Dermatology

Disclosure: Nothing to disclose.

Michael T Yen, MD Professor and The Sarah Campbell Blaffer Chair in Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, Medical Director, Alkek Eye Center, Co-Director, BCM Aesthetics, Program Director, ASOPRS Fellowship, Baylor College of Medicine

Michael T Yen, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Sling Therapeutics; Ipsen Innovation<br/>Received research grant from: Viridian Therapeutics.

Natalie Ana Baugh California State University, Long Beach

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

Kenneth C Earhart, MD Deputy Head, Disease Surveillance Program, United States Naval Medical Research Unit #3

Kenneth C Earhart, MD is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Undersea and Hyperbaric Medical Society

Disclosure: Nothing to disclose.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

John M Leedom, MD Professor Emeritus of Medicine, Keck School of Medicine of the University of Southern California

John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rhinocerebral Mucormycosis Clinical Presentation

History

Physical Examination

References

Tables

Contributor Information and Disclosures

What would you like to print?