eMedicine Specialties > Ophthalmology > Infectious Disease

Mucormycosis

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

Updated: Dec 31, 2008

Introduction

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.¹ 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.2 Of those patients with mucormycosis, 50-75% 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.³

Race

No racial predisposition is known.

Sex

No sex predisposition is known.

Age

No age predisposition is known.

Clinical

History

• Early diagnosis and treatment is the key. This diagnosis requires a high degree of clinical suspicion.^4,5,6,7
• Common symptoms include the following:
  • Orbital and facial pain
  • Sinusitis
  • Headache
  • Fever
  • Visual changes
  • Nasal discharge or stuffiness

Physical

• External examination may reveal the following⁸ :
  • Periorbital and facial swelling with signs of orbital cellulitis (eg, proptosis, ophthalmoplegia)⁹
  • Fever
  • Change in mental status
  • Necrotic tissue can be seen on the nasal turbinates, septum, and palate and may look like a black eschar.
• Ocular examination may reveal the following:
  • Decreased vision
  • Afferent pupillary defect
  • Conjunctival chemosis
  • Proptosis and periorbital edema
  • Decreased ocular motility/partial or total ophthalmoplegia
  • Orbital apex syndrome

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.
• Patients with immunosuppression and/or metabolic abnormalities are at risk. Other patients at risk include the following:
  • Patients on long-term antibiotics, steroids, or cytotoxic therapy
  • Patients with chronic renal failure or liver problems
  • Patients with transplants
  • Patients with cancer
  • Patients with HIV
  • Patients with malnutrition or acidosis, especially diabetic patients with ketoacidosis (historically considered patients at highest risk)

Differential Diagnoses

Cellulitis, Orbital
Cellulitis, Preseptal

Other Problems to Be Considered

Other fungal infections
Hypercoagulable states

Workup

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.
• Perform MRI to evaluate vessels, fat, and intracranial extension.

Procedures

• Perform urgent exploration and biopsy if mucormycosis is suspected.
  • Send frozen and permanent sections and fresh tissue.
  • If clinical suspicion is high, but initial specimens are negative, take additional specimens, to include the arteries.

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.

Treatment

Medical Care

• Complete treatment of underlying medical disease. Correct hypoxia, acidosis, hyperglycemia, and electrolyte abnormalities.
• Any steroid medication, antimetabolites, or immunosuppressants that the patient is on should be addressed and discontinued if appropriate.
• 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.^10,11,12
• Frontal sinus involvement and older patients have lower rates of survival.
• 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.
• Hyperbaric oxygen has been suggested as a potential treatment, but its exact role remains unclear.

Surgical Care

• Aggressive surgical debridement of all necrotic tissue is necessary, sometimes requiring multiple debridements.
  • Because of the vasoocclusive effect of mucormycosis, the involved tissue rarely bleeds, so debridement until normal, well-perfused, bleeding tissue is encountered is ideal.
  • Surgery often may be disfiguring.
• Intraorbital irrigation of amphotericin B may be considered as an adjunct treatment.^13,14,10
• Orbital exenteration, along with removal of the sinuses, may be necessary.  No standard exists to guide physicians on the best timing of exenteration.^15,16,17,18
• Consider reconstructive surgery only after complete resolution of infection.¹⁹

Consultations

• A multidisciplinary approach is the best. Specialties to consider include the following:
  • Ophthalmology for evaluation of ophthalmoplegia and optic neuropathy
  • Oculoplastic surgery for orbital evaluation, debridement, and reconstruction
  • Otolaryngology for biopsy or debridement of nasal/sinus cavities
  • Infectious disease, internal medicine, and endocrinology for medical management of underlying systemic etiologies
  • Neurosurgery if intracranial involvement present
  • Pharmacotherapy consult to assist with dosing of amphotericin B

Diet

Control diabetes if it is an underlying disease.

Medication

Although aggressive surgical intervention is required, patients also should receive adjuvant antifungal therapy.

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.

Amphotericin B, liposomal (Amphocin, Fungizone)

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.

Dosing

Adult

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

Pediatric

Administer as in adults

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

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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 CBC counts

Follow-up

Further Inpatient Care

• Serial imaging and evaluation is performed as needed to assess the extent of the disease and to decide if reoperation is necessary.
• After amphotericin B is discontinued, close assessment for recurrence needs to be performed.
• Treatment often is long term and disfiguring.

Further Outpatient Care

• Closely manage the patient's underlying medical condition and medications.
• Reconstructive surgery, if necessary, can be considered only after complete resolution of infection.

Inpatient & Outpatient Medications

• See Medical Care.

Complications

• Intracranial invasion
• Cavernous sinus thrombosis
• Blindness
• Central retinal artery occlusion
• Airway obstruction from head and neck infections
• Spread to carotid sheath or mediastinum through fascial planes

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.^20,21

Patient Education

• Immediately evaluate patients at risk if any signs or symptoms develop.

Miscellaneous

Medicolegal Pitfalls

• The clinician must retain a high clinical suspicion for mucormycosis in patients at risk. A delay in diagnosis may be fatal and could result in liability claims against the physician.

Special Concerns

• Early treatment and detection is the key.

Multimedia

Media file 1: CT scan of a patient who is suspected of having mucormycosis shows extensive involvement of the right orbit and adjacent sinuses.

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.

Media file 3: Characteristic appearance of mucormycosis under the microscope.

References

1. Gilbard SM, Della Rocca RC. Paranasal sinus disease and the orbit. In: Nesi FA, et al, ed. Smith's Ophthalmic Plastic and Reconstructive Surgery. 2^nd ed. 1998:896-930.

2. Rocha G, Garza G, Font RL. Orbital pathology associated with diabetes mellitus. Int Ophthalmol Clin. Spring 1998;38(2):169-79. [Medline].

3. Yohai RA, Bullock JD, Aziz AA, et al. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. Jul-Aug 1994;39(1):3-22. [Medline].

4. Guevara N, Roy D, Dutruc-Rosset C, et al. Mucormycosis--early diagnosis and treatment. Rev Laryngol Otol Rhinol (Bord). 2004;125(2):127-31. [Medline].

5. Turunc T, Demiroglu YZ, Aliskan H, et al. Eleven cases of mucormycosis with atypical clinical manifestations in diabetic patients. Diabetes Res Clin Pract. Nov 2008;82(2):203-8. [Medline].

6. Nithyanandam S, Jacob MS, Battu RR, et al. Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features and treatment outcomes. Indian J Ophthalmol. Sep 2003;51(3):231-6. [Medline].

7. Bhansali A, Sharma A, Kashyap A, et al. Mucor endophthalmitis. Acta Ophthalmol Scand. Feb 2001;79(1):88-90. [Medline].

8. Arndt S, Aschendorff A, Echternach M, et al. Rhino-orbital-cerebral mucormycosis and aspergillosis: differential diagnosis and treatment. Eur Arch Otorhinolaryngol. Jan 2009;266(1):71-6. [Medline].

9. Doty CI, Lucchesi M. Mucormycosis manifesting as proptosis and unilateral blindness. Acad Emerg Med. Aug 2000;7(8):944-6. [Medline].

10. Strasser MD, Kennedy RJ, Adam RD. Rhinocerebral mucormycosis. Therapy with amphotericin B lipid complex. Arch Intern Med. Feb 12 1996;156(3):337-9. [Medline].

11. Tarani L, Costantino F, Notheis G, et al. Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girl. Pediatr Diabetes. Sep 17 2008;[Medline].

12. Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. Aug 1 2008;47(3):364-71. [Medline].

13. Luna JD, Ponssa XS, Rodriguez SD, et al. Intraconal amphotericin B for the treatment of rhino-orbital mucormycosis. Ophthalmic Surg Lasers. Aug 1996;27(8):706-8. [Medline].

14. Seiff SR, Choo PH, Carter SR. Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthal Plast Reconstr Surg. Jan 1999;15(1):28-31. [Medline].

15. Hargrove RN, Wesley RE, Klippenstein KA, et al. Indications for orbital exenteration in mucormycosis. Ophthal Plast Reconstr Surg. Jul-Aug 2006;22(4):286-91. [Medline].

16. Pelton RW, Peterson EA, Patel BC, et al. Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities. Ophthal Plast Reconstr Surg. Jan 2001;17(1):62-6. [Medline].

17. Hargrove RN, Wesley RE, Klippenstein KA, et al. Indications for orbital exenteration in mucormycosis. Ophthal Plast Reconstr Surg. Jul-Aug 2006;22(4):286-91. [Medline].

18. Croce A, Moretti A, D'Agostino L, et al. Orbital exenteration in elderly patients: personal experience. Acta Otorhinolaryngol Ital. Aug 2008;28(4):193-9. [Medline].

19. Lari AR, Kanjoor JR, Vulvoda M, et al. Orbital reconstruction following sino-nasal mucormycosis. Br J Plast Surg. Jan 2002;55(1):72-5. [Medline].

20. Dhiwakar M, Thakar A, Bahadur S. Improving outcomes in rhinocerebral mucormycosis--early diagnostic pointers and prognostic factors. J Laryngol Otol. Nov 2003;117(11):861-5. [Medline].

21. Fairley C, Sullivan TJ, Bartley P, et al. Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient. Ophthalmology. Mar 2000;107(3):555-8. [Medline].

Keywords

mucormycosis , Mucor, rhinocerebral mucormycosis, rhino-orbital cerebral mucormycosis

Contributor Information and Disclosures

Author

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.

Coauthor(s)

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 Cataract and Refractive Surgery, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

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 Medical Association, American Society of Ophthalmic Plastic and Reconstructive Surgery, Colorado Medical Society, Utah Medical Association, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

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
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.

Managing Editor

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 Consulting fee Consulting; Quest medical - lacrimal balloons Honoraria Speaking and teaching; Ortho-Neutrogenia Consulting fee Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

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.

The authors and editors of eMedicine gratefully acknowledge the assistance of Ryan I Huffman, MD, with the literature review and referencing for this article.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)