Mucormycosis Workup

  • Author: Nancy F Crum-Cianflone; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Aug 8, 2011
 

Approach Considerations

Timely diagnosis is paramount in cases of mucormycosis. Persons with suspected rhinocerebral disease should undergo an emergent CT scanning of the paranasal sinuses and an endoscopic examination of their nasal passages with biopsies of any suggestive lesions. The diagnosis of mucormycosis is established by obtaining a biopsy specimen of the involved tissue, and frozen tissue samples should be immediately evaluated for signs of infection. Tissue should also be sent for routine pathology examination and cultures. Swabs of tissue or discharge are unreliable.

For pulmonary disease, a bronchoalveolar lavage (BAL), biopsy, or both may assist in the diagnosis.

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Laboratory Tests

A complete blood cell (CBC) count should be obtained to assess for neutropenia. A chemistry panel that includes blood glucose, bicarbonate, and electrolytes is useful to monitor homeostasis and direct correction of acidosis. An arterial blood gases (ABG) study can help determine the degree of acidosis and direct corrective treatments.

Iron studies may be indicated to assess the presence of iron overload as shown by high ferritin levels and a low total iron-binding capacity.

In cases of central nervous system (CNS) involvement, cerebrospinal fluid (CSF) findings may include elevated protein levels and a modest mononuclear pleocytosis. CSF cultures are typically sterile. A computed tomography (CT) scan should precede a lumbar puncture to ensure that this procedure is safe.

Blood cultures can be obtained; however, they are usually negative despite the angioinvasive nature of the organism. Antigen tests (beta-D-glucan or galactomannan) are not useful for detecting this infection.

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Radiologic Studies

Rhinocerebral infections

Plain films may show sinus involvement with mucosal thickening, air-fluid levels, and/or bony erosions.

Head and facial computed tomographic (CT) scanning should be used as the initial investigation in rhinocerebral infections. CT scans may show sinusitis of the ethmoid and sphenoid sinuses, as well as orbital and intracranial extension. As the disease progresses, bony erosion may occur and the infection may spread into the brain or orbits. In addition, because mucormycosis organisms have a predilection for vascular involvement, thromboses of the cavernous sinus or internal carotid artery may occur.[10] All of the areas of involvement must be understood in order to plan the extent of surgical debridement.

Magnetic resonance imaging (MRI) of the facial sinuses and brain is superior to a CT scan in assessing the need for ongoing surgery.

Pulmonary disease

Obtain chest radiography and chest high-resolution CT scanning. The most common finding is consolidation, usually unilobar; with disease progression, multilobar involvement may develop. Cavitation, especially producing an air crescent or halo sign, is highly suggestive of fungal infection but does not distinguish it from aspergillosis. Nodular lesions (especially multiple nodules) and pleural effusions may be present. See the images below.

Chest computed tomography (CT) scan showing pulmonChest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions. Chest computed tomography (CT) scan showing pulmonChest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions. This CT scan of the patient shows resolution of pulmonary mucormycosis after 5 months of antifungal treatment.

Gastrointestinal disease

In gastrointestinal (GI) disease, abdominal CT scans may show a mass associated with the GI tract.

Central nervous system

CT scanning or MRI of the central nervous system may reveal abscesses (especially in the setting of intravenous drug use) or extension of rhinocerebral disease into the brain. Additionally, cavernous and, less commonly, sagittal sinus thrombosis may be seen.

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Biopsy and Histologic Features

The critical test procedure for diagnosing mucormycosis is obtaining a biopsy specimen of the involved tissue. A rapid histologic assessment of a frozen tissue section should be performed in order to promptly institute surgical and medical management for the infection.

Biopsy of necrotic tissue

Biopsy of necrotic tissue may be obtained from nasal, palatine, lung, cutaneous, gastrointestinal (GI), or abscess wall site.

Stains of fixed tissues with hematoxylin and eosin (H&E) or specialized fungal stains, such as Grocott methenamine-silver (see the following image) or periodic acid-Schiff (PAS) stains, show pathognomonic changes of broad-based (typically 10- to 20-µm diameter), irregular, ribbonlike, nonseptate hyphae with irregular branching that may occur at right angles. Vascular invasion and necrosis are the characteristic consequences of the infective process. Thus, neutrophil infiltration, vessel invasion, and tissue infarction are often observed. A granulomatous reaction may also be observed.

Histologic findings from an immunocompetent man whHistologic findings from an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Findings show the typical Mucorales hyphae on Grocott methenamine-silver staining. The hyphae are the dark structures with budlike, right-angle hyphae. (Courtesy of A. Allworth, MD, Brisbane, Australia.)

Culture of biopsy samples is required to determine the species of Mucorales. Do not crush or grind the specimen, because the nonseptate hyphae are prone to damage. Growth usually occurs in 2-3 days. The genus and species are determined via examination of the fungal morphology (eg, the presence and location of the rhizoids).

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Contributor Information and Disclosures
Author

Nancy F Crum-Cianflone  MD, MPH, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego

Nancy F Crum-Cianflone is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Mark T Duffy, MD, PhD  Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal and Reconstructive Surgery, Green Bay Eye Clinic, BayCare Clinic; Medical Director, Advanced Cosmetic Solutions, A BayCare Clinic

Mark T Duffy, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Ophthalmic Plastic and Reconstructive Surgery, Sigma Xi, and Society for Neuroscience

Disclosure: Allergan - Botox Cosmetic Honoraria Speaking and teaching

Simon K Law, MD, PharmD  Associate Professor of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Ron W Pelton, MD, PhD  Private Practice, Colorado Springs, Colorado

Ron W Pelton, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Society of Ophthalmic Plastic and Reconstructive Surgery, AO Foundation, and Colorado Medical Society

Disclosure: Nothing to disclose.

Kimberly G Yen, MD  Assistant Professor of Ophthalmology, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine

Kimberly G Yen, MD is a member of the following medical societies: Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Michael T Yen, MD  Associate Professor of Ophthalmology, Department of Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, 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, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Specialty Editor Board

Maria D Mileno, MD  Associate Professor of Medicine, Division of Infectious Diseases, The Warren Alpert Medical School of Brown University

Maria D Mileno, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society of Travel Medicine, and Sigma Xi

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

Ronald A Greenfield, MD  Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References
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  12. Sedlacek M, Cotter JG, Suriawinata AA, et al. Mucormycosis peritonitis: more than 2 years of disease-free follow-up after posaconazole salvage therapy after failure of liposomal amphotericin B. Am J Kidney Dis. Feb 2008;51(2):302-6. [Medline].

  13. Rickerts V, Atta J, Herrmann S, et al. Successful treatment of disseminated mucormycosis with a combination of liposomal amphotericin B and posaconazole in a patient with acute myeloid leukaemia. Mycoses. 2006;49 Suppl 1:27-30. [Medline].

  14. Ashkenazi-Hoffnung L, Bilavsky E, Avitzur Y, Amir J. Successful treatment of cutaneous zygomycosis with intravenous amphotericin B followed by oral posaconazole in a multivisceral transplant recipient. Transplantation. Nov 27 2010;90(10):1133-5. [Medline].

  15. Yoon YK, Kim MJ, Chung YG, Shin IY. Successful treatment of a case with rhino-orbital-cerebral mucormycosis by the combination of neurosurgical intervention and the sequential use of amphotericin B and posaconazole. J Korean Neurosurg Soc. Jan 2010;47(1):74-7. [Medline]. [Full Text].

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Postmortem photograph of a woman with diabetes and left rhinocerebral mucormycosis complicating ketoacidosis. Rhizopus oryzae was the causative organism. Note the orbital and facial cellulitis and the black nasal discharge. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
The right eye of an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Note the proptosis. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
The right eye of an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Chemosis is shown in this photograph. Internal and external ophthalmoplegia, no light perception, and afferent pupil defect were present, which is consistent with orbital apex syndrome. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
An immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. A surgical field of this patient is shown. Excision of the right orbit, maxillary antrum, nasal cavity, sphenoid sinus, and infratemporal fossa has taken place. The tissue was infarcted. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
An immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Picture of the patient after successful treatment with repeated surgical debridement and high-dose liposomal amphotericin B. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
Histologic findings from an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Findings show the typical Mucorales hyphae on Grocott methenamine-silver staining. The hyphae are the dark structures with budlike, right-angle hyphae. (Courtesy of A. Allworth, MD, Brisbane, Australia.)
Chest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions.
Chest computed tomography (CT) scan showing pulmonary mucormycosis with left basal consolidation and widespread nodules due to Rhizopus oryzae infection. The patient was receiving cytotoxic chemotherapy for myelodysplastic syndrome and had iron overload from numerous blood transfusions. This CT scan of the patient shows resolution of pulmonary mucormycosis after 5 months of antifungal treatment.
 
 
 
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