KERATITIS AND ENDOPHTHALMITIS CAUSED BY
PETRIELLIDIUM
BOYDII
I. D . E L L I O T T , F . R . A . C . S . , C . HALDE, PH.D., AND J . S H A P I R O , M . D .
San Francisco,
Petriellidium boydii (formerly known as Allescheria boydii) and its imperfect form, Monosporium apiospermum, are pathogenic for man and animals only when their accidental implantation into tissue leads to a mycetoma, or when they are acting as opportunists. One mycetoma of the palpebral conjunctiva believed to be caused by P. boydii was reported in 1 9 6 8 ; before 1975, eight cases of Petriellidium keratomycosis, all of them following either corneal injury or herpetic keratitis, had been d e s c r i b e d . Topical corticosteroid therapy facilitates infection by opportunistic fungi, but one of these eight patients reported that no corticosteroids had been used.
California from the inferior conjunctival cul-de-sac grew P. boydii and Staphylococcus epidermidis. A second culture of material from the cul-de-sac two days later also grew P. boydii, but corneal material was negative by both direct microscopy and culture. On Oct. 23, we discontinued the prednisolone acetate eyedrops, and administered topical gentamicin sulfate (Garamycin), chloramphenicol (Chloromycetin), polymyxin B sulfate (Neosporin), and amphotericin B was begun two days later. The eye became increasingly painful and developed aringof necrosis around the periphery of the cornea. Because of severe pain and impending corneal perforation, the eye was enucleated on Oct. 29. No cultures were made of material from the enucleated eye.
1
2-9
Histopathology—Histological examination of the enucleated eye showed corneal perforations with iris prolapse superiorly and inferiorly in the region of the ring abscess. The central cornea consisted of a thin necrotic stroma (heavily infiltrated with inflammatory cells) and Descemet's membrane. Hyphae with septae were seen in the deep stroma near the corneoscleral limbus and many were also found on the anterior surface of Descemet's membrane. Some hyphae lay within Descemet's membrane and a few were seen in the anterior chamber (Figure). The anterior chamber was obliterated in its inferior half by a fibrous hypopyon showing early organization. T h e ciliary body and vitreous body were acutely inflamed.
This clinicopathologic report concerns an eye that developed keratomycosis and endophthalmitis caused by P. boydii after a severe eyelid and corneoconjunctival burn with molten aluminum. CASE REPORT
A 26-year-old man sustained burns of the left eye and eyelids from molten aluminum on Oct. 11,1972, and was admitted to the hospital. Visual acuity in the injured eye was hand movements. On Oct. 13, we administered sulfisoxazole diomide (Gantrisin Ophthalmic Ointment), prednisolone acetate (Prednefrin Forte), and 1% atropine eyedrops, all given four times daily. During the initial 13 days, the cornea remained edematous and failed to epithelialize; conjunctival Symblepharon developed and the eyelid margins sloughed. About Oct. 24, infiltrates began to appear in the cornea near the corneoscleral limbus but separated from it. A culture of material collected on Oct. 25
Mycology—On Oct. 2 5 , about 100 white colonies, darkening to gray or black, appeared on a Sabouraud's agar plate inoculated with material swabbed from the inferior conjunctival cul-de-sac. Numerous pale brown, truncated aleuriospores developed from simple conidiophores or laterally along the hyphae. In old cultures, whorls of sterigmas, each with one conidium, covered the length of the conidiophores.
From the Department of Ophthalmology (Drs. Elliott and Shapiro) and the Department of Microbiology (Dr. Halde), University of California, San Francisco. Dr. Elliott was a Hearst Fellow (1972). Reprint requests to Carlyn Halde, Ph.D., Department of Microbiology, University of California San Francisco, San Francisco, CA 94143. 16
VOL. 83, NO. 1
KERATITIS AND ENDOPHTHALMITIS
17
ly, cultures were not made of the cornea at enucleation, but we believe that the hyphae seen in sections were from the same fungus responsible for the infection. Histological examination o f the enucleated eye after three days o f antifungal therapy showed hyphae only in the deep part of the necrotic cornea. Although it appeared that the medication had eradicated the fungus from the surface of the lesion, the absence of identifiable mycological forms anywhere in this layer suggested that the layer had never been infected by the fungus. A histological s t u d y of 72 cases of mycotic keratitis showed that there is considerable variation in the distribution of hyphae within infected corneas but that in most cases they are deep in the corneal parenchyma and conspicuously absent on the surface. 11
Figure (Elliott, Halde, and Shapiro). Hyphae within Descemet's membrane (Giemsa stain, x800).
The conidia were ovate to clávate and 5 to 12 (x long. Numerous dark brown cleistothecia began to develop within two weeks. On rupture by pressure, these revealed asci containing eight pale brown, elliptical ascospores, 6 to 8 u. long. Coremia were present. These characteristics were sufficient to identify the fungus as P. boydii. T h e same fungus was recovered from cultures two days later. DISCUSSION
Keratomycosis caused by P. boydii results experimentally when the rabbit cornea has been injured, inoculated with the fungus, and then treated with cortisone. In the eight clinical cases previously retrauma or herpetic keratitis ported, were antecedent. Five of the eight had received corticosteroids topically; although corticosteroids were reportedly "not used" in one of the other cases, their use or nonuse was not mentioned in two of the three reports. In our case the fungus was isolated from material taken from the inferior conjunctival cul-de-sac 14 days after the eye was burned and after ten days of treatment with a corticosteroid. Unfortunate10
2-9
7
Since conidiospores, as well as hyphae, were seen in scrapings from three infectit seems that P. boydii ed c o r n e a s , appears in three different ways within infected human tissue: (1) as compact colonies of hyphae (granules in mycetoma); (2) as filamentous hyphae only; and (3) as hyphae and conidiospores. Only two of the nine cases of keratomycosis caused by P. boydii (including our own) were successfully treated. Amphotericin B and nystatin were used in both. Ernest and R i p p o n reported that their isolate was subsequently insensitive to amphotericin B but sensitive to nystatin. N i e l s e n found that all of his 15 isolates of P. boydii or M. apiospermum, from a variety of sources, were sensitive to amphotericin B at 100 |xg/ml or less, but two of the 15 were sensitive to 3 u.g/ml. T h e isolates of the imperfect form, M. apiospermum, were more likely to be sensitive to diluted amphotericin B than the isolates of P. boydii. Since the currently available amphotericin B is not readily soluble in water, its penetration of corneal stroma cannot be expected to be 1,3,7
7
11
18
AMERICAN JOURNAL O F
OPHTHALMOLOGY
good. A water-soluble form of the drug should be more effective. SUMMARY
A 26-year-old man sustained burns of the left eye and eyelids from molten aluminum. Antimicrobial and anti-inflammatory therapy was instituted. Cultures of conjunctival material collected 14 days after the burn grew abundant colonies of Petriellidium boydii. Because of severe pain and impending corneal perforation, the eye was enucleated.
REFERENCES
1. Persaud, V., and Holroyd, J. B. M.: Mycetoma of the palpebral conjunctiva. Br. J. Ophthalmol. 52:857, 1968. 2. Pautler, E . E., Roberts, R. W., and Beamer, P. R.: Mycotic infection of the eye. Monosporium
OPHTHALMIC
JANUARY, 1977
apiospermum associated with corneal ulcer. Arch. Ophthalmol. 53:385, 1955. 3. Gordon, M. A., Valloton, W. W., and Croffead, G. S.: Corneal allescheriosis. Arch. Ophthalmol. 62:758, 1959. 4. Casero, L.: Keratomycosis. Its recently increased incidence and its treatment with new antifungal antibiotics. Arch. Soc. Oftalmol. Hisp. Am. 22:293, 1962. 5. Zimmerman, L. E.: Keratomycosis. Survey Ophthalmol. 8:1, 1963. 6. Hairstone, M. A., and De Voe, A. G.: Keratomycosis. An ultrastructural study. Ophthalmologica 152:197, 1966. 7. Ernest, J. T., and Rippon, J. W.: Keratitis due to Allescheria boydii (Monosporium apiospermum). Am. J. Ophthalmol. 62:1202, 1966. 8. Levitt, J. M.: Keratomycosis due to Allescheria boydii. Am. J. Ophthalmol. 71:1190, 1971. 9. Bakerspigel, A.: Fungi isolated from keratomycosis in Ontario, Canada. 1. Monosporium apiospermum (Allescheria boydii). Sabouraudia9:109,1971. 10. Ley, A. P.: Experimental fungus infection of the cornea. Am. J. Ophthalmol. 42:59, 1956. 11. Nielsen, H. S.: Effects of amphotericin B on perfect and imperfect strains of Allescheria boydii. Appl. Microbiol. 15:86, 1967.
MINIATURE
Seeing E y e . . . In spite of its wide usage, this is not a generic term for dogs especially trained to lead the blind. T h e Seeing E y e , in Morristown, New Jersey, is only one of several organizations devoted to training such dogs. There are also Guide Dogs, which come from a group in California, and Leader Dogs, out of the Midwest. T . Burnam, The Dictionary of Mis-Information New York, Crowell Co., 1 9 7 5
PETRIELLIDIUM
BOYDII
I. D . E L L I O T T , F . R . A . C . S . , C . HALDE, PH.D., AND J . S H A P I R O , M . D .
San Francisco,
Petriellidium boydii (formerly known as Allescheria boydii) and its imperfect form, Monosporium apiospermum, are pathogenic for man and animals only when their accidental implantation into tissue leads to a mycetoma, or when they are acting as opportunists. One mycetoma of the palpebral conjunctiva believed to be caused by P. boydii was reported in 1 9 6 8 ; before 1975, eight cases of Petriellidium keratomycosis, all of them following either corneal injury or herpetic keratitis, had been d e s c r i b e d . Topical corticosteroid therapy facilitates infection by opportunistic fungi, but one of these eight patients reported that no corticosteroids had been used.
California from the inferior conjunctival cul-de-sac grew P. boydii and Staphylococcus epidermidis. A second culture of material from the cul-de-sac two days later also grew P. boydii, but corneal material was negative by both direct microscopy and culture. On Oct. 23, we discontinued the prednisolone acetate eyedrops, and administered topical gentamicin sulfate (Garamycin), chloramphenicol (Chloromycetin), polymyxin B sulfate (Neosporin), and amphotericin B was begun two days later. The eye became increasingly painful and developed aringof necrosis around the periphery of the cornea. Because of severe pain and impending corneal perforation, the eye was enucleated on Oct. 29. No cultures were made of material from the enucleated eye.
1
2-9
Histopathology—Histological examination of the enucleated eye showed corneal perforations with iris prolapse superiorly and inferiorly in the region of the ring abscess. The central cornea consisted of a thin necrotic stroma (heavily infiltrated with inflammatory cells) and Descemet's membrane. Hyphae with septae were seen in the deep stroma near the corneoscleral limbus and many were also found on the anterior surface of Descemet's membrane. Some hyphae lay within Descemet's membrane and a few were seen in the anterior chamber (Figure). The anterior chamber was obliterated in its inferior half by a fibrous hypopyon showing early organization. T h e ciliary body and vitreous body were acutely inflamed.
This clinicopathologic report concerns an eye that developed keratomycosis and endophthalmitis caused by P. boydii after a severe eyelid and corneoconjunctival burn with molten aluminum. CASE REPORT
A 26-year-old man sustained burns of the left eye and eyelids from molten aluminum on Oct. 11,1972, and was admitted to the hospital. Visual acuity in the injured eye was hand movements. On Oct. 13, we administered sulfisoxazole diomide (Gantrisin Ophthalmic Ointment), prednisolone acetate (Prednefrin Forte), and 1% atropine eyedrops, all given four times daily. During the initial 13 days, the cornea remained edematous and failed to epithelialize; conjunctival Symblepharon developed and the eyelid margins sloughed. About Oct. 24, infiltrates began to appear in the cornea near the corneoscleral limbus but separated from it. A culture of material collected on Oct. 25
Mycology—On Oct. 2 5 , about 100 white colonies, darkening to gray or black, appeared on a Sabouraud's agar plate inoculated with material swabbed from the inferior conjunctival cul-de-sac. Numerous pale brown, truncated aleuriospores developed from simple conidiophores or laterally along the hyphae. In old cultures, whorls of sterigmas, each with one conidium, covered the length of the conidiophores.
From the Department of Ophthalmology (Drs. Elliott and Shapiro) and the Department of Microbiology (Dr. Halde), University of California, San Francisco. Dr. Elliott was a Hearst Fellow (1972). Reprint requests to Carlyn Halde, Ph.D., Department of Microbiology, University of California San Francisco, San Francisco, CA 94143. 16
VOL. 83, NO. 1
KERATITIS AND ENDOPHTHALMITIS
17
ly, cultures were not made of the cornea at enucleation, but we believe that the hyphae seen in sections were from the same fungus responsible for the infection. Histological examination o f the enucleated eye after three days o f antifungal therapy showed hyphae only in the deep part of the necrotic cornea. Although it appeared that the medication had eradicated the fungus from the surface of the lesion, the absence of identifiable mycological forms anywhere in this layer suggested that the layer had never been infected by the fungus. A histological s t u d y of 72 cases of mycotic keratitis showed that there is considerable variation in the distribution of hyphae within infected corneas but that in most cases they are deep in the corneal parenchyma and conspicuously absent on the surface. 11
Figure (Elliott, Halde, and Shapiro). Hyphae within Descemet's membrane (Giemsa stain, x800).
The conidia were ovate to clávate and 5 to 12 (x long. Numerous dark brown cleistothecia began to develop within two weeks. On rupture by pressure, these revealed asci containing eight pale brown, elliptical ascospores, 6 to 8 u. long. Coremia were present. These characteristics were sufficient to identify the fungus as P. boydii. T h e same fungus was recovered from cultures two days later. DISCUSSION
Keratomycosis caused by P. boydii results experimentally when the rabbit cornea has been injured, inoculated with the fungus, and then treated with cortisone. In the eight clinical cases previously retrauma or herpetic keratitis ported, were antecedent. Five of the eight had received corticosteroids topically; although corticosteroids were reportedly "not used" in one of the other cases, their use or nonuse was not mentioned in two of the three reports. In our case the fungus was isolated from material taken from the inferior conjunctival cul-de-sac 14 days after the eye was burned and after ten days of treatment with a corticosteroid. Unfortunate10
2-9
7
Since conidiospores, as well as hyphae, were seen in scrapings from three infectit seems that P. boydii ed c o r n e a s , appears in three different ways within infected human tissue: (1) as compact colonies of hyphae (granules in mycetoma); (2) as filamentous hyphae only; and (3) as hyphae and conidiospores. Only two of the nine cases of keratomycosis caused by P. boydii (including our own) were successfully treated. Amphotericin B and nystatin were used in both. Ernest and R i p p o n reported that their isolate was subsequently insensitive to amphotericin B but sensitive to nystatin. N i e l s e n found that all of his 15 isolates of P. boydii or M. apiospermum, from a variety of sources, were sensitive to amphotericin B at 100 |xg/ml or less, but two of the 15 were sensitive to 3 u.g/ml. T h e isolates of the imperfect form, M. apiospermum, were more likely to be sensitive to diluted amphotericin B than the isolates of P. boydii. Since the currently available amphotericin B is not readily soluble in water, its penetration of corneal stroma cannot be expected to be 1,3,7
7
11
18
AMERICAN JOURNAL O F
OPHTHALMOLOGY
good. A water-soluble form of the drug should be more effective. SUMMARY
A 26-year-old man sustained burns of the left eye and eyelids from molten aluminum. Antimicrobial and anti-inflammatory therapy was instituted. Cultures of conjunctival material collected 14 days after the burn grew abundant colonies of Petriellidium boydii. Because of severe pain and impending corneal perforation, the eye was enucleated.
REFERENCES
1. Persaud, V., and Holroyd, J. B. M.: Mycetoma of the palpebral conjunctiva. Br. J. Ophthalmol. 52:857, 1968. 2. Pautler, E . E., Roberts, R. W., and Beamer, P. R.: Mycotic infection of the eye. Monosporium
OPHTHALMIC
JANUARY, 1977
apiospermum associated with corneal ulcer. Arch. Ophthalmol. 53:385, 1955. 3. Gordon, M. A., Valloton, W. W., and Croffead, G. S.: Corneal allescheriosis. Arch. Ophthalmol. 62:758, 1959. 4. Casero, L.: Keratomycosis. Its recently increased incidence and its treatment with new antifungal antibiotics. Arch. Soc. Oftalmol. Hisp. Am. 22:293, 1962. 5. Zimmerman, L. E.: Keratomycosis. Survey Ophthalmol. 8:1, 1963. 6. Hairstone, M. A., and De Voe, A. G.: Keratomycosis. An ultrastructural study. Ophthalmologica 152:197, 1966. 7. Ernest, J. T., and Rippon, J. W.: Keratitis due to Allescheria boydii (Monosporium apiospermum). Am. J. Ophthalmol. 62:1202, 1966. 8. Levitt, J. M.: Keratomycosis due to Allescheria boydii. Am. J. Ophthalmol. 71:1190, 1971. 9. Bakerspigel, A.: Fungi isolated from keratomycosis in Ontario, Canada. 1. Monosporium apiospermum (Allescheria boydii). Sabouraudia9:109,1971. 10. Ley, A. P.: Experimental fungus infection of the cornea. Am. J. Ophthalmol. 42:59, 1956. 11. Nielsen, H. S.: Effects of amphotericin B on perfect and imperfect strains of Allescheria boydii. Appl. Microbiol. 15:86, 1967.
MINIATURE
Seeing E y e . . . In spite of its wide usage, this is not a generic term for dogs especially trained to lead the blind. T h e Seeing E y e , in Morristown, New Jersey, is only one of several organizations devoted to training such dogs. There are also Guide Dogs, which come from a group in California, and Leader Dogs, out of the Midwest. T . Burnam, The Dictionary of Mis-Information New York, Crowell Co., 1 9 7 5
