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Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient1
Survival after Rhino-Orbital-Cerebral Mucormycosis in an Immunocompetent Patient Cliff Fairley, MBBS,1 Timothy J. Sullivan, FRACO,1 Paul Bartley, MBBS,2 Tony Allworth, FRACP, FRCPA,2 Richard Lewandowski, FRACS3 Objective: Rhino-orbital-cerebral mucormycosis is usually associated with a poor prognosis and is almost exclusively seen in immunocompromised patients. We report the third documented case of rhino-orbital-cerebral mucormycosis caused by Apophysomyces elegans (a new genus of the family Mucoraceae first isolated in 1979) in an immunocompetent individual. Orbital exenteration and radical debridement of involved adjacent structures combined with intravenous liposomal amphotericin resulted in patient survival. Design: Interventional case report. Method: A 59-year-old immunocompetent white man sustained a high-pressure water jet injury to the right inner canthus while cleaning an air conditioner filter. He later had “orbital cellulitis” develop that did not respond to antibiotics and progressed to orbital infarction. Imaging studies and biopsy results led to a diagnosis of mucormycosis. Tissue culture grew Apophysomyces elegans, a new genus of the family Mucoraceae first isolated in 1979. Orbital exenteration and radical debridement of involved adjacent structures, combined with intravenous liposomal amphotericin, resulted in patient survival. Results: After orbital exenteration and debridement of involved adjacent structures along with intravenous liposomal amphotericin, our patient has remained free from relapse with long-term follow-up. Conclusions: The agent causing this case of rhino-orbital-cerebral mucormycosis (Apophysomyces elegans) contrasts with the three genera most commonly responsible for mucormycosis (Rhizopus, Mucor, and Absidia) in that infections with this agent tend to occur in warm climates, by means of traumatic inoculation, and in immunocompetent patients. Rhino-orbital-cerebral mucormycosis should be considered in all patients with orbital inflammation associated with multiple cranial nerve palsies and retinal or orbital infarction, regardless of their immunologic status. A team approach to management is recommended for early, appropriate surgery and systemic antifungal agents. Ophthalmology 2000;107:555–558 © 2000 by the American Academy of Ophthalmology.
Case Report A 59-year-old white male pest control operator with no significant medical history sustained a high-pressure water jet injury to the right inner canthus while cleaning an air conditioner filter. Twelve hours later he had sharp, deep retro-orbital pain. The following day when reviewed by his Originally received: June 30, 1999. Accepted: November 11, 1999. Manuscript no. 99360. 1 Eyelid, Lacrimal and Orbital Clinic, Division of Ophthalmology, Division of Surgery, Royal Brisbane Hospital, Brisbane, Australia. 2 Infectious Diseases Unit, Division of Medicine, Royal Brisbane Hospital, Brisbane, Australia. 3 Division of Plastic & Reconstructive Surgery, Division of Surgery, Royal Brisbane Hospital, Brisbane, Australia. Presented at the 4th annual meeting of the Australian Society of Ophthalmic Plastic and Reconstructive Surgery, Brisbane, Australia, October 1998, and at the Australasian Society for Infectious Diseases Annual Scientific Meeting, Hobart, Australia, October 1998. None of the authors has a commercial interest in any product described in the article. Reprint requests to Dr. T. J. Sullivan, 7th Floor, 135 Wickham Terrace, Brisbane, QL 4000, Australia. © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
local physician, he was apyrexial and had mild right eyelid swelling. He was prescribed oral cephalexin. Over the following 3 days, he experienced increasing discomfort, became febrile (up to 39°C ), and developed marked right-sided periorbital edema, erythema, and proptosis. His Snellen visual acuity was 20/15 bilaterally. A diagnosis of periorbital cellulitis was made. He was admitted and started on intravenous broad-spectrum antibiotics. Two blood cultures were negative, and a conjunctival swab was noncontributory. Blood glucose and serum electrolytes and creatinine were normal. His hemoglobin and leukocyte count were within normal limits. Proptosis and chemosis progressed over the subsequent 3 days, and his visual acuity deteriorated to light perception in his right eye. He remained febrile and had a dilated, unreactive pupil. Funduscopy demonstrated a pale retina with attenuated retinal vessels consistent with central retinal artery occlusion. A computed tomography (CT) scan of the orbits was performed (Fig 1), which demonstrated marked proptosis, chemosis, and no intraorbital fluid collections or masses. There was extensive mucosal thickening in his right ethmoid and maxillary sinuses. Nine days after the onset of symptoms he was transferred ISSN 0161-6420/00/$–see front matter PII S0161-6420(99)00142-6
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Ophthalmology Volume 107, Number 3, March 2000
Figure 3. T1-weighted axial magnetic resonance imaging through the midorbits.
Figure 1. A, Axial computed tomography scan through the midorbits with soft tissue windows. B, Coronal computed tomography scan through the midorbits with soft tissue windows.
to our hospital. He was alert and orientated. His right eye had marked proptosis with internal and external ophthalmoplegia, no light perception, and a 4⫹ relative afferent pupil defect consistent with orbital apex syndrome (Fig 2). No ulceration/necrosis of his oral or nasal mucosa was
Figure 2. Clinical photograph on presentation at our hospital.
556
noted. Full blood examination revealed white blood cell count, 16.1 (normal range, 3.5–11 ⫻ 106/l); neutrophils, 13.1 (normal range, 2–7.5 ⫻ 106/l;) monocytes, 1.43 (normal range, 0.05– 0.9 ⫻ 106/l); and pH, 7.49. Serum biochemistry was normal. Magnetic resonance imaging (MRI ) demonstrated right proptosis, infiltrated orbital fat, and enlarged extraocular muscles (Fig 3). The process involved the entire orbit and extended into his right maxillary antrum, nasal cavity, sphenoid sinus, and infratemporal fossa. There was no intracranial involvement. Urgent right orbital exploration and biopsy revealed infarcted necrotic tissue with a distinct lack of bleeding. Histologic examination revealed broad, nonseptate hyphae with branching at 90 degrees involving blood vessel walls, consistent with mucormycosis (Fig 4). He underwent orbital exenteration and radical debridement of involved adjacent structures. A cerebrospinal fluid leak was found after division of the optic nerve. The surgical defect was packed with amphotericin-soaked Surgicel. Intravenous liposomal amphotericin (AmBisome, NeXstar, San Dimas, CA) 350 mg daily (5 mg/kg/day) was begun.
Figure 4. Histologic findings of orbital tissue biopsy showing fungal hyphae. (Stain, Grocott methenamine silver; original magnification, ⫻250.)
Fairley et al 䡠 Mucormycosis in an Immunocompetent Patient
Figure 5. Clinical photograph on discharge from our hospital.
Orbital tissue subsequently grew a filamentous mold with the morphologic characteristics of the imperfect phase of Apophysomyces elegans. The patient underwent two further de´bridements of the infratemporal fossa and histologic examination was negative for fungal hyphae. His right facial defect was grafted with a free rectus abdominus flap; this aided in obliterating the residual dead space with highly vascularized tissue, which in turn assisted in the delivery of amphotericin to the infection site (Fig 5). He was treated with 42 days of liposomal amphotericin; his total amphotericin dose was 14.7 g, and he was discharged 49 days after transfer. He has remained free of disease after 12 months of follow-up.
Discussion Rhino-orbital-cerebral mucormycosis (ROCM) caused by the more traditional genera of the family Mucoraceae (Rhizopus, Mucor, and Absidia) is the most acutely fatal fungal infection in humans.1– 4 Despite many advances in diagnosis and treatment, individuals contracting ROCM still have a high mortality, and it is reportedly becoming a more common disease for a number of postulated reasons. The use of antibiotics, steroids, immunosuppressive, and antineoplastic drugs, along with the increased longevity of debilitated patients, has been incriminated as predisposing factors.4 This case of ROCM is noteworthy in that it was caused by A. elegans, a new genus of the family Mucoraceae first isolated in 1979.5 In our analysis of the literature, it represents the third case of ROCM caused by A. elegans.1,6,7 A. elegans was first isolated in India. Misra et al5 in 1979 demonstrated this new fungus in soil samples collected from a mango orchard. Sixteen human infections caused by A. elegans have been reported, all but one in immunocompetent patients. Skin and soft tissue infections distant to the head and neck, resulting from a combination of traumatic inoculation and solid contamination, are the most widely reported manifestations of the disease.4,6,8 In contrast to infections with most other genera of the Mucoraceae family, ROCM caused by A. elegans is uncommon, having been
reported on only two previous occasions.6 Among the clinical spectrum of ROCM, the cases caused by A. elegans are noteworthy for the following reasons. First, ROCM caused by the more common genera (Rhizopus, Mucor, and Absidia) tends to occur almost exclusively among patients with well-recognized immunologic or metabolic abnormalities.1,3,9 The major predisposing factors to Mucormycosis developing, namely hyperglycemia, ketoacidosis, corticosteroid therapy, malignancy, leukopenia, and immunosuppressive drugs, are uncommonly found in patients with infections caused by A. elegans.1,6,9 The two previously reported cases of ROCM caused by A. elegans have occurred in immunocompetent patients. The first was a previously healthy 19-year-old man from Guadalajara, Mexico, after traumatic inoculation and soil contamination reported in 1995.1 The second case, in 1997, involved an immunocompetent 60-year-old man from the Northern Territory, Australia. It remains unclear how the infection was acquired in this case.7 Second, classical ROCM is thought to spread by means of aerosol transmission of spores and typically begins in the nasal or oral mucosa.2 From the paranasal sinuses, ROCM spreads into the orbits and/or cranial cavity, a process greatly facilitated by the organism’s propensity to invade blood vessels, notably arteries, and to propagate within vessel walls and lumens. Ischemic infarction of the tissue normally supplied by the affected vessels becomes superimposed on septic necrosis. Death results from disease extension into the brain and fungal invasion of cerebral arteries leading to rupture, hemorrhage, and occlusions.3,9,10 Most reported cases of mucormycosis caused by A. elegans have resulted from traumatic inoculation and/or soil contamination. Finally, A. elegans is a thermophilic fungus and, contrasting with ROCM caused by other genera, all clinical cases have been reported from countries with warm climates.8 Of paramount importance in the management of ROCM is early diagnosis, which requires a high degree of clinical suspicion. The most common presenting signs and symptoms of ROCM include orbital cellulitis, periorbital and facial swelling, external ophthalmoplegia, decreased vision, central retinal artery occlusion, orbital apex syndrome, proptosis, chemosis, fever, nasal mucosal ulceration/necrosis, sinusitis, headache, facial/orbital pain, and change in mental state.2,3 Early visual loss and retinal artery occlusion would favor a diagnosis of ROCM over bacterial cavernous sinus thrombosis in which blindness is a much later finding.9,11–13 Orbital findings are the result of ischemic necrosis of the intraorbital contents and cranial nerves. Therefore, it is important for the ophthalmologist to consider the possibility of ROCM, irrespective of immune status, in all the following clinical situations: orbital cellulitis (especially if not responding to antibiotics), mixed cranial nerve palsies, and cases of retinal or orbital infarction. When ROCM is suspected on clinical grounds, laboratory personnel should be alerted so that optimal mycologic procedures can be used.8 It is important the tissue specimen is directly inoculated onto the media with the avoidance of
557
Ophthalmology Volume 107, Number 3, March 2000 excessive specimen chopping or grinding. This is thought to damage the hyphae and render the fungi nonviable, resulting in false-negative cultures.6,14 Although treatment modalities have not undergone clinical trials, aggressive surgical debridement, amphotericinsoaked packs, and intravenous amphotericin B therapy is considered appropriate treatment for ROCM.2,15 Kohn and Hepler16 presented excellent results by adding daily amphotericin irrigation and packing of the involved orbit and sinuses. This likely aids the delivery of amphotericin B to poorly perfused infected and or necrotic tissue. Liposomal amphotericin may result in increased efficacy. Amphotericin B encapsulated in liposomes significantly decreases toxicity, enabling higher dosages to be administered. Liposomal encapsulation appears to enhance delivery to fungi, infected organs, and phagocytes.2 The prognosis of ROCM has improved greatly. In 1961, the mortality was 88% and now varies from 15% to 34%.11 The mortality of ROCM caused specifically by A. elegans is currently unknown because of the rarity of diagnosed cases, but it would seem to fall at the more favorable end of the spectrum. In conclusion, rapidly progressive ROCM can occur in otherwise healthy individuals. Clinicians should consider ROCM caused by A. elegans (especially in warm climates) in all patients with invasive orbital disease, regardless of their immunologic status, because prompt surgical and medical intervention is essential for cure. Acknowledgment. The authors thank Dr. Andrew Lomas, Consultant Ear, Nose and Throat Surgeon, for his role in patient management.
References 1. Radner AB, Witt MD, Edwards JE Jr. Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case report and review. Clin Infect Dis 1995;20:163– 6. 2. Yohai RA, Bullock JD, Aziz AA, Marker RJ. Survival factors
558
3.
4.
5. 6.
7.
8.
9.
10.
11. 12. 13. 14.
15.
16.
in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol 1994;39:3–22. Ferry AP, Abedi S. Diagnosis and management of rhinoorbitocerebral mucormycosis (phycomycosis). A report of 16 personally observed cases. Ophthalmology 1983;90:1096 – 1104. Wieden MA, Steinbronn KK, Padhye AA, et al. Zygomycosis caused by Apophysomyces elegans. J Clin Microbiol 1985;22: 522– 6. Misra PC, Srivastava KJ, Lata K. Apophysomyces, a new genus of the Mucorales. Mycotaxon 1979;8:377– 82. Holland J. Emerging zygomycoses of humans: Saksenaea vasiformis and Apophysomyces elegans. Curr Top Med Mycol 1997;8:27–34. Sdralis T, Krishnan S, Holland J. “Martini glass” mucormycoses—Apophysomyces elegans infection in an immune competent host. Aust J Otolaryngol 1997;2:600 –2. Weinberg WG, Wade BH, Cierny G III, Rinaldi MG. Invasive infection due to Apophysomyces elegans in immunocompetent hosts. Clin Infect Dis 1993;17:881– 4. Johnson EV, Kline LB, Julian BA, Garcia JH. Bilateral cavernous sinus thrombosis due to mucormycosis. Arch Ophthalmol 1988;106:1089 –92. Hussain S, Salahuddin N, Ahmad I, et al. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur J Radiol 1995;20:151–5. Bray WH, Giangiacomo J, Ide CH. Orbital apex syndrome. Surv Ophthalmol 1987;32:136 – 40. Lehrer RI, Howard DH, Sypherd PS, et al. Mucormycosis. Ann Intern Med 1980;93:93–108. Kline MW. Mucormycosis in children: review of the literature and report of cases. Pediatr Infect Dis 1985;4:672– 6. Cook BA, White CB, Blaney SM, Bass JW. Survival after isolated cerebral mucormycosis. Am J Pediatr Hematol Oncol 1989;11:330 –3. O’Keefe M, Haining WM, Young JDH, Guthrie W. Orbital mucormycosis with survival. Br J Ophthalmol 1986; 70:634 – 6. Kohn R, Hepler R. Management of limited rhino-orbital mucormycosis without exenteration. Ophthalmology 1985;92: 1440 – 4.
Case Report A 59-year-old white male pest control operator with no significant medical history sustained a high-pressure water jet injury to the right inner canthus while cleaning an air conditioner filter. Twelve hours later he had sharp, deep retro-orbital pain. The following day when reviewed by his Originally received: June 30, 1999. Accepted: November 11, 1999. Manuscript no. 99360. 1 Eyelid, Lacrimal and Orbital Clinic, Division of Ophthalmology, Division of Surgery, Royal Brisbane Hospital, Brisbane, Australia. 2 Infectious Diseases Unit, Division of Medicine, Royal Brisbane Hospital, Brisbane, Australia. 3 Division of Plastic & Reconstructive Surgery, Division of Surgery, Royal Brisbane Hospital, Brisbane, Australia. Presented at the 4th annual meeting of the Australian Society of Ophthalmic Plastic and Reconstructive Surgery, Brisbane, Australia, October 1998, and at the Australasian Society for Infectious Diseases Annual Scientific Meeting, Hobart, Australia, October 1998. None of the authors has a commercial interest in any product described in the article. Reprint requests to Dr. T. J. Sullivan, 7th Floor, 135 Wickham Terrace, Brisbane, QL 4000, Australia. © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
local physician, he was apyrexial and had mild right eyelid swelling. He was prescribed oral cephalexin. Over the following 3 days, he experienced increasing discomfort, became febrile (up to 39°C ), and developed marked right-sided periorbital edema, erythema, and proptosis. His Snellen visual acuity was 20/15 bilaterally. A diagnosis of periorbital cellulitis was made. He was admitted and started on intravenous broad-spectrum antibiotics. Two blood cultures were negative, and a conjunctival swab was noncontributory. Blood glucose and serum electrolytes and creatinine were normal. His hemoglobin and leukocyte count were within normal limits. Proptosis and chemosis progressed over the subsequent 3 days, and his visual acuity deteriorated to light perception in his right eye. He remained febrile and had a dilated, unreactive pupil. Funduscopy demonstrated a pale retina with attenuated retinal vessels consistent with central retinal artery occlusion. A computed tomography (CT) scan of the orbits was performed (Fig 1), which demonstrated marked proptosis, chemosis, and no intraorbital fluid collections or masses. There was extensive mucosal thickening in his right ethmoid and maxillary sinuses. Nine days after the onset of symptoms he was transferred ISSN 0161-6420/00/$–see front matter PII S0161-6420(99)00142-6
555
Ophthalmology Volume 107, Number 3, March 2000
Figure 3. T1-weighted axial magnetic resonance imaging through the midorbits.
Figure 1. A, Axial computed tomography scan through the midorbits with soft tissue windows. B, Coronal computed tomography scan through the midorbits with soft tissue windows.
to our hospital. He was alert and orientated. His right eye had marked proptosis with internal and external ophthalmoplegia, no light perception, and a 4⫹ relative afferent pupil defect consistent with orbital apex syndrome (Fig 2). No ulceration/necrosis of his oral or nasal mucosa was
Figure 2. Clinical photograph on presentation at our hospital.
556
noted. Full blood examination revealed white blood cell count, 16.1 (normal range, 3.5–11 ⫻ 106/l); neutrophils, 13.1 (normal range, 2–7.5 ⫻ 106/l;) monocytes, 1.43 (normal range, 0.05– 0.9 ⫻ 106/l); and pH, 7.49. Serum biochemistry was normal. Magnetic resonance imaging (MRI ) demonstrated right proptosis, infiltrated orbital fat, and enlarged extraocular muscles (Fig 3). The process involved the entire orbit and extended into his right maxillary antrum, nasal cavity, sphenoid sinus, and infratemporal fossa. There was no intracranial involvement. Urgent right orbital exploration and biopsy revealed infarcted necrotic tissue with a distinct lack of bleeding. Histologic examination revealed broad, nonseptate hyphae with branching at 90 degrees involving blood vessel walls, consistent with mucormycosis (Fig 4). He underwent orbital exenteration and radical debridement of involved adjacent structures. A cerebrospinal fluid leak was found after division of the optic nerve. The surgical defect was packed with amphotericin-soaked Surgicel. Intravenous liposomal amphotericin (AmBisome, NeXstar, San Dimas, CA) 350 mg daily (5 mg/kg/day) was begun.
Figure 4. Histologic findings of orbital tissue biopsy showing fungal hyphae. (Stain, Grocott methenamine silver; original magnification, ⫻250.)
Fairley et al 䡠 Mucormycosis in an Immunocompetent Patient
Figure 5. Clinical photograph on discharge from our hospital.
Orbital tissue subsequently grew a filamentous mold with the morphologic characteristics of the imperfect phase of Apophysomyces elegans. The patient underwent two further de´bridements of the infratemporal fossa and histologic examination was negative for fungal hyphae. His right facial defect was grafted with a free rectus abdominus flap; this aided in obliterating the residual dead space with highly vascularized tissue, which in turn assisted in the delivery of amphotericin to the infection site (Fig 5). He was treated with 42 days of liposomal amphotericin; his total amphotericin dose was 14.7 g, and he was discharged 49 days after transfer. He has remained free of disease after 12 months of follow-up.
Discussion Rhino-orbital-cerebral mucormycosis (ROCM) caused by the more traditional genera of the family Mucoraceae (Rhizopus, Mucor, and Absidia) is the most acutely fatal fungal infection in humans.1– 4 Despite many advances in diagnosis and treatment, individuals contracting ROCM still have a high mortality, and it is reportedly becoming a more common disease for a number of postulated reasons. The use of antibiotics, steroids, immunosuppressive, and antineoplastic drugs, along with the increased longevity of debilitated patients, has been incriminated as predisposing factors.4 This case of ROCM is noteworthy in that it was caused by A. elegans, a new genus of the family Mucoraceae first isolated in 1979.5 In our analysis of the literature, it represents the third case of ROCM caused by A. elegans.1,6,7 A. elegans was first isolated in India. Misra et al5 in 1979 demonstrated this new fungus in soil samples collected from a mango orchard. Sixteen human infections caused by A. elegans have been reported, all but one in immunocompetent patients. Skin and soft tissue infections distant to the head and neck, resulting from a combination of traumatic inoculation and solid contamination, are the most widely reported manifestations of the disease.4,6,8 In contrast to infections with most other genera of the Mucoraceae family, ROCM caused by A. elegans is uncommon, having been
reported on only two previous occasions.6 Among the clinical spectrum of ROCM, the cases caused by A. elegans are noteworthy for the following reasons. First, ROCM caused by the more common genera (Rhizopus, Mucor, and Absidia) tends to occur almost exclusively among patients with well-recognized immunologic or metabolic abnormalities.1,3,9 The major predisposing factors to Mucormycosis developing, namely hyperglycemia, ketoacidosis, corticosteroid therapy, malignancy, leukopenia, and immunosuppressive drugs, are uncommonly found in patients with infections caused by A. elegans.1,6,9 The two previously reported cases of ROCM caused by A. elegans have occurred in immunocompetent patients. The first was a previously healthy 19-year-old man from Guadalajara, Mexico, after traumatic inoculation and soil contamination reported in 1995.1 The second case, in 1997, involved an immunocompetent 60-year-old man from the Northern Territory, Australia. It remains unclear how the infection was acquired in this case.7 Second, classical ROCM is thought to spread by means of aerosol transmission of spores and typically begins in the nasal or oral mucosa.2 From the paranasal sinuses, ROCM spreads into the orbits and/or cranial cavity, a process greatly facilitated by the organism’s propensity to invade blood vessels, notably arteries, and to propagate within vessel walls and lumens. Ischemic infarction of the tissue normally supplied by the affected vessels becomes superimposed on septic necrosis. Death results from disease extension into the brain and fungal invasion of cerebral arteries leading to rupture, hemorrhage, and occlusions.3,9,10 Most reported cases of mucormycosis caused by A. elegans have resulted from traumatic inoculation and/or soil contamination. Finally, A. elegans is a thermophilic fungus and, contrasting with ROCM caused by other genera, all clinical cases have been reported from countries with warm climates.8 Of paramount importance in the management of ROCM is early diagnosis, which requires a high degree of clinical suspicion. The most common presenting signs and symptoms of ROCM include orbital cellulitis, periorbital and facial swelling, external ophthalmoplegia, decreased vision, central retinal artery occlusion, orbital apex syndrome, proptosis, chemosis, fever, nasal mucosal ulceration/necrosis, sinusitis, headache, facial/orbital pain, and change in mental state.2,3 Early visual loss and retinal artery occlusion would favor a diagnosis of ROCM over bacterial cavernous sinus thrombosis in which blindness is a much later finding.9,11–13 Orbital findings are the result of ischemic necrosis of the intraorbital contents and cranial nerves. Therefore, it is important for the ophthalmologist to consider the possibility of ROCM, irrespective of immune status, in all the following clinical situations: orbital cellulitis (especially if not responding to antibiotics), mixed cranial nerve palsies, and cases of retinal or orbital infarction. When ROCM is suspected on clinical grounds, laboratory personnel should be alerted so that optimal mycologic procedures can be used.8 It is important the tissue specimen is directly inoculated onto the media with the avoidance of
557
Ophthalmology Volume 107, Number 3, March 2000 excessive specimen chopping or grinding. This is thought to damage the hyphae and render the fungi nonviable, resulting in false-negative cultures.6,14 Although treatment modalities have not undergone clinical trials, aggressive surgical debridement, amphotericinsoaked packs, and intravenous amphotericin B therapy is considered appropriate treatment for ROCM.2,15 Kohn and Hepler16 presented excellent results by adding daily amphotericin irrigation and packing of the involved orbit and sinuses. This likely aids the delivery of amphotericin B to poorly perfused infected and or necrotic tissue. Liposomal amphotericin may result in increased efficacy. Amphotericin B encapsulated in liposomes significantly decreases toxicity, enabling higher dosages to be administered. Liposomal encapsulation appears to enhance delivery to fungi, infected organs, and phagocytes.2 The prognosis of ROCM has improved greatly. In 1961, the mortality was 88% and now varies from 15% to 34%.11 The mortality of ROCM caused specifically by A. elegans is currently unknown because of the rarity of diagnosed cases, but it would seem to fall at the more favorable end of the spectrum. In conclusion, rapidly progressive ROCM can occur in otherwise healthy individuals. Clinicians should consider ROCM caused by A. elegans (especially in warm climates) in all patients with invasive orbital disease, regardless of their immunologic status, because prompt surgical and medical intervention is essential for cure. Acknowledgment. The authors thank Dr. Andrew Lomas, Consultant Ear, Nose and Throat Surgeon, for his role in patient management.
References 1. Radner AB, Witt MD, Edwards JE Jr. Acute invasive rhinocerebral zygomycosis in an otherwise healthy patient: case report and review. Clin Infect Dis 1995;20:163– 6. 2. Yohai RA, Bullock JD, Aziz AA, Marker RJ. Survival factors
558
3.
4.
5. 6.
7.
8.
9.
10.
11. 12. 13. 14.
15.
16.
in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol 1994;39:3–22. Ferry AP, Abedi S. Diagnosis and management of rhinoorbitocerebral mucormycosis (phycomycosis). A report of 16 personally observed cases. Ophthalmology 1983;90:1096 – 1104. Wieden MA, Steinbronn KK, Padhye AA, et al. Zygomycosis caused by Apophysomyces elegans. J Clin Microbiol 1985;22: 522– 6. Misra PC, Srivastava KJ, Lata K. Apophysomyces, a new genus of the Mucorales. Mycotaxon 1979;8:377– 82. Holland J. Emerging zygomycoses of humans: Saksenaea vasiformis and Apophysomyces elegans. Curr Top Med Mycol 1997;8:27–34. Sdralis T, Krishnan S, Holland J. “Martini glass” mucormycoses—Apophysomyces elegans infection in an immune competent host. Aust J Otolaryngol 1997;2:600 –2. Weinberg WG, Wade BH, Cierny G III, Rinaldi MG. Invasive infection due to Apophysomyces elegans in immunocompetent hosts. Clin Infect Dis 1993;17:881– 4. Johnson EV, Kline LB, Julian BA, Garcia JH. Bilateral cavernous sinus thrombosis due to mucormycosis. Arch Ophthalmol 1988;106:1089 –92. Hussain S, Salahuddin N, Ahmad I, et al. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur J Radiol 1995;20:151–5. Bray WH, Giangiacomo J, Ide CH. Orbital apex syndrome. Surv Ophthalmol 1987;32:136 – 40. Lehrer RI, Howard DH, Sypherd PS, et al. Mucormycosis. Ann Intern Med 1980;93:93–108. Kline MW. Mucormycosis in children: review of the literature and report of cases. Pediatr Infect Dis 1985;4:672– 6. Cook BA, White CB, Blaney SM, Bass JW. Survival after isolated cerebral mucormycosis. Am J Pediatr Hematol Oncol 1989;11:330 –3. O’Keefe M, Haining WM, Young JDH, Guthrie W. Orbital mucormycosis with survival. Br J Ophthalmol 1986; 70:634 – 6. Kohn R, Hepler R. Management of limited rhino-orbital mucormycosis without exenteration. Ophthalmology 1985;92: 1440 – 4.