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Ophthalmology > INFECTIOUS DISEASE
Mucormycosis
Article Last Updated: Aug 22, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Kimberly G Yen, MD, Assistant Professor of Ophthalmology, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine
Kimberly G Yen is a member of the following medical societies: Association for Research in Vision and Ophthalmology
Coauthor(s):
Michael T Yen, MD, Assistant Professor of Ophthalmology, Department of Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, Baylor College of Medicine
Editors: Ron W Pelton, MD, PhD, Consulting Staff, Department of Surgery, Memorial Hospital; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Mark T Duffy, MD, PhD, Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal, and Reconstructive Surgery, Green Bay Eye Clinic, BayCare Clinic; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
Mucor, mucormycosis, rhinocerebral mucormycosis, rhino-orbital cerebral mucormycosis
Background
Mucormycosis is an aggressive, opportunistic infection caused by fungi in the class of Phycomycetes, first described in 1885 by Paltauf. The genera most commonly responsible for mucormycosis usually are Mucor or Rhizopus.
Orbitorhinocerebral mucormycosis, the most common type, generally occurs in conjunction with sinus or nasal involvement. Mucormycosis also may affect other parts of the body, including the lungs, GI tract, or skin.
Most cases of mucormycosis are acute surgical emergencies; however, several cases of a more chronic, indolent form have been reported, with signs and symptoms developing over 4 weeks.
Pathophysiology
The spores of these fungi are ubiquitous and gain entrance to the human body through the mouth and the nose. Individuals who are immunocompetent will phagocytize these spores; therefore, they do not develop the disease. In individuals who are immunocompromised, germination and hyphae formation occur, and this allows the organism to invade the patient's blood vessels. Mucormycosis is described almost exclusively in patients with compromised immune systems or metabolic abnormalities.
The spores attach to the nasal or oral mucosa where massive spore formation occurs; then, the fungus directly invades the blood vessels. Spread occurs when it invades the nasal cavity and maxillary sinuses. Extension to ethmoid sinuses can lead to orbital involvement. Intracranial spread can occur through the ophthalmic artery, superior fissure, or cribriform plate. Areas of ischemic infarction and necrosis are seen in the infected tissue. The fungi invade the blood vessel lumina and cause thrombosis through inflammatory occlusion.
Frequency
United States
Exact frequency is unknown but is higher in patients with immune compromise or metabolic abnormalities. Fifty percent to 75% of patients have poorly controlled diabetes mellitus and ketoacidosis. Diabetic patients are predisposed to mucormycosis because of the decreased ability of their neutrophils to phagocytize and adhere to endothelial walls. Furthermore, the acidosis and hyperglycemia provide an excellent environment for the fungus to grow.
Mortality/Morbidity
Despite advances in diagnosis and treatment, a high mortality still exists for this disease. Death may occur within 2 weeks if untreated or unsuccessfully treated.
- Until the 1950s, this disease almost always was a fatal disease. Permanent residual effects of the disease occur up to 70% of the time. These effects include blindness and cranial nerve defects.
- Mortality rates of 30-70% are quoted in the literature, with mortality higher in older series. The mortality rate in diabetic patients appears to be lower than in nondiabetic patients and in patients with intracerebral involvement. Patients who have been treated with amphotericin B and who have had orbital exenterations are more likely to survive.
- In a meta-analysis by Yohai et al, it was believed that the survival rate declines when interval from diagnosis to treatment is longer than 6 days.16
Race
No predisposition is known.
Sex
No predisposition is known.
Age
No predisposition is known.
History
- Early diagnosis and treatment is the key. This diagnosis requires a high degree of clinical suspicion.
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- Common symptoms include the following:
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- Orbital and facial pain
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- Sinusitis
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- Headache
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- Fever
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- Visual changes
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- Nasal discharge or stuffiness
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Physical
- External examination may reveal the following:
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- Periorbital and facial swelling with signs of orbital cellulitis (eg, proptosis, ophthalmoplegia)
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- Fever
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- Change in mental status
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- Necrotic tissue can be seen on the nasal turbinates, septum, and palate and may look like a black eschar.
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- Ocular examination
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- Decreased vision
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- Afferent pupillary defect
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- Conjunctival chemosis
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- Proptosis and periorbital edema
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- Decreased ocular motility/partial or total ophthalmoplegia
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- Orbital apex syndrome
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Causes
- Mucormycosis is an aggressive, opportunistic infection caused by fungi in the class of Phycomycetes. The genera most commonly responsible for mucormycosis usually are Mucor or Rhizopus.
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- Immunosuppression and/or metabolic abnormalities
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- Other patients at risk include the following:
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- Patients on chronic antibiotics, steroids, or cytotoxic therapy
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- Patients with chronic renal failure or liver problems
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- Patients with transplants
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- Patients with cancer
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- Patients with HIV
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- Patients with malnutrition or acidosis, especially diabetic patients with ketoacidosis who have historically been considered patients at highest risk
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Cellulitis, Orbital
Cellulitis, Preseptal
Other Problems to be Considered
Other fungal infections
Hypercoagulable states
Lab Studies
- Urgent biopsy of involved necrotic-appearing tissue is necessary.
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- Perform histological evaluation and culture of the tissue.
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- Nonseptate hyphae with branching at 90° are seen on Grocott-Gomori methenamine-silver stain.
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Imaging Studies
- Perform CT scan to evaluate soft tissue extent, mucosal thickening, bone erosion, intracranial/cavernous sinus involvement, and sinus disease. In general, bone erosion is a late finding.
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- Perform MRI to evaluate vessels, fat, and intracranial extension.
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Other Tests
Procedures
- Perform urgent exploration and biopsy if mucormycosis is suspected.
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- Send frozen and permanent sections and fresh tissue.
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- If clinical suspicion is high, but initial specimens are negative, take additional specimens, to include the arteries.
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Histologic Findings
Necrotic and edematous tissue with neutrophilic infiltrate is seen. The fungus has broad, nonseptate hyphae with branching at 90°. Grocott-Gomori methenamine-silver stain is the best stain to use, but hematoxylin and eosin and periodic acid-Schiff also may be used. Blood vessels appear thrombosed, and hyphae may be seen invading the vessels. Growth of this fungus occurs best in brain-heart infusion agar, potato dextrose agar, or Sabouraud dextrose agar.
Medical Care
- Complete treatment of underlying medical disease. Correct hypoxia, acidosis, hyperglycemia, and electrolyte abnormalities.
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- Any steroid medication, antimetabolites, or immunosuppressants that the patient is on should be addressed and discontinued if appropriate.
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- The use of systemic amphotericin B is important in treating mucormycosis; its use, along with increased awareness of the disease, has decreased the mortality. The highest possible tissue levels should be achieved. Remember to assess for nephrotoxicity. Other systemic toxicities include fever, nausea and vomiting, phlebitis, anemia, and electrolyte abnormalities. Liposomal amphotericin B may be more efficacious; it is less toxic, allowing higher doses of the medication to be given.
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- Consider local irrigation and packing of the areas to aid delivery of amphotericin to necrotic and poorly perfused tissues. Because poor vascular supply may prevent systemic therapy from reaching the fungus, local irrigation of infected tissue has been reported as an important adjunct to treatment and may even prevent disfiguring surgery.
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- Hyperbaric oxygen has been suggested as a potential treatment, but its exact role remains unclear.
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Surgical Care
- Aggressive surgical debridement of all necrotic tissue is necessary, sometimes requiring multiple debridements.
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- Because of the vasoocclusive effect of mucormycosis, the involved tissue rarely bleeds, so debridement until normal, well-perfused, bleeding tissue is encountered is ideal.
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- Surgery often may be disfiguring.
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- Intraorbital irrigation of amphotericin B may be considered as an adjunct treatment.
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- Orbital exenteration, along with removal of sinuses, may be necessary.
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- Consider reconstructive surgery only after complete resolution of infection.
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Consultations
- A multidisciplinary approach is the best. Specialties to consider include the following:
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- Ophthalmology for evaluation of ophthalmoplegia and optic neuropathy
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- Oculoplastic surgery for orbital evaluation, debridement, and reconstruction
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- Otolaryngology for biopsy or debridement of nasal/sinus cavities
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- Infectious disease, internal medicine, and endocrinology for medical management of underlying systemic etiologies
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- Neurosurgery if intracranial involvement present
- Pharmacotherapy consult to assist with dosing of amphotericin B
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Diet
Control diabetes if it is an underlying disease.
Although aggressive surgical intervention is required, patients also should receive adjuvant antifungal therapy.
Drug Category: Antifungals
Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
| Drug Name | Amphotericin B, liposomal (Amphocin, Fungizone) |
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| Description | Intravenous liposomal amphotericin B is produced from Streptomyces nodosus. Provided as a sterile suspension containing 100 mg/20 mL of amphotericin B. Acts by binding to sterols in the cell membrane of the fungi, resulting in a change in permeability of the membrane. Drug resistant species of have been isolated in patients receiving prolonged therapy. |
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| Adult Dose | Recommended daily dose is 5 mg/kg IV infusion at a rate of 2.5 mg/kg/h; if infusion time exceeds 2 h, then shake infusion bag to mix contents q2h |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | Administer under close clinical observation for acute reactions, usually more common with the first few doses; laboratory analyses should include serum creatine, liver profile, serum electrolytes, and complete blood counts |
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Further Inpatient Care
- Serial imaging and evaluation is preformed as needed to assess the extent of the disease and to decide if reoperation is necessary.
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- After amphotericin B is discontinued, close assessment for recurrence needs to be performed.
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- Treatment often is long term and disfiguring.
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Further Outpatient Care
- Closely manage the patient's underlying medical condition and medications.
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- Reconstructive surgery, if necessary, can be considered only after complete resolution of infection.
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In/Out Patient Meds
Complications
- Intracranial invasion
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- Cavernous sinus thrombosis
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- Blindness, central retinal artery occlusion
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- Airway obstruction from infections of head and neck
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- Spread to carotid sheath or mediastinum through fascial planes
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Prognosis
- Prognosis is guarded in these patients; however, with early detection and early treatment, the survival rate may be improved. Over the last 40 years, prognosis has improved greatly.
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Patient Education
- Immediately evaluate patients at risk if any signs or symptoms develop.
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Medical/Legal Pitfalls
- The clinician must retain a high clinical suspicion for mucormycosis in patients at risk. Delay in diagnosis may be fatal and could result in liability claims against the physician.
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Special Concerns
- Early treatment and detection is the key.
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| Media file 1:
CT scan of a patient who is suspected of having mucormycosis shows extensive involvement of the right orbit and adjacent sinuses. |
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Media type: CT
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| Media file 2:
This diabetic patient with mucormycosis presented with complete ophthalmoplegia and proptosis. Note the complete ptosis and periorbital edema on the right side. |
 | View Full Size Image | |
Media type: Photo
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| Media file 3:
Characteristic appearance of mucormycosis under the microscope. |
 | View Full Size Image | |
Media type: Photo
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Mucormycosis excerpt Article Last Updated: Aug 22, 2006
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