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Bacterial Pseudomycosis of the Orbit
504
AMERICAN JOURNAL OF OPHTHALMOLOGY
posterior subcapsular zone, with or without vacuoles, and 29 were free of such changes. The presence of lens changes was correlated with the known duration of disease and du ration of therapy with the two major chemotherapeutic agents utilized, Myleran and dibromomannitol. A possible role of these chemotherapeutic drugs in the production of human lens changes was suggested, although effects of the leukemic process on the lens could not be ruled out. ACKNOWLEDGMENTS
The suggestions of Drs. Ludwig von Sallmann and Paul Carbone are gratefully acknowledged. REFERENCES
1. Galton, D. A. G. : Myleran in chronic myeloid leukemia: Results of treatment. Lancet 1:208, 1953. 2. Casazza, A. R., Cahn, E. L. and Carbone, P. P. : Preliminary studies with dibromomannitol (NSC94100) in patients with chronic myelogenous leu kemia. Cancer Chemother. Rep. 51:91, 1967.
SEPTEMBER, 1969
3. Sallmann, L. von : The lens epithelium in the pathogenesis of cataract: The XIII Edward Jack son Memorial Lecture. Am. J. Ophth. 44:159, 1957. 4. Grimes, P., von Sallmann, L. and Frichette, A. : Influence of Myleran on cell proliferation in the lens epithelium. Invest. Ophth. 3:566, 1964. 5. Grimes, P. and von Sallmann, L. : Interference with cell proliferation and induction of polyploidy in rat lens epithelium during prolonged Myleran treatment. Exp. Cell Res. 42:265, 1966. 6. Light, A. E. : Additional observations on the effects of busulfan on cataract formation, duration of anesthesia, and reproduction in rats. Toxic. Appi. Pharmacol. 10:459, 1967. 7. Sallmann, L. von and Grimes, P. : Some effects of anticancer drugs on cell proliferation in the eye : An experimental study. Ophthalmologica Addit. 151:917, 1966. 8. Huguley, C. M. et al : Comparison of 6-mercaptopurine and busulfan in chronic granulocytic leukemia. Blood 21:89,1963. 9. Borgeson, E. J. and Wagener, H. P.: Changes in the eye in leukemia. Am. J. Med. Sci. 177:663, 1929. 10. Allen, R. A. and Straatsma, B. R.: Ocular involvement in leukemia and allied disorders. Arch. Ophth. 66:490, 1961.
BACTERIAL PSEUDOMYCOSIS O F T H E ORBIT HENRY A. KALLET, M.D.,
K E I T H S. MCKENZIE, M.D.,
AND FRANK D. JOHNSON,
M.D.
Ann Arbor, Michigan
Bacterial pseudomycosis is a chronic granulomatous and suppurative bacterial in flammation of the skin and subcutaneous tis sues or, more rarely, of soft tissue or vis cera, in which the specific feature is the presence of funguslike grains or granules within suppurative foci. These granules con tain nonbranching bacteria enclosed in a hyaline matrix and closely mimic those fun gal grains seen in actinomycosis, nocardiosis or mycetoma. The lesion was first described by Bollinger1 in 1870. In 1884 Rivolta2 encoun tered the characteristic grains in pus obFrom the Departments of Pathology and Oph thalmology, The University of Michigan Medical Center and Veterans Administration Hospital. Reprint requests to Henry A. Kallet, M.D., De partment of Pathology, 1335 East Catherine Street, Ann Arbor, Michigan 48104.
tained from infected castration wounds in horses. Believed to be fungal in origin, the infection was called botryomycosis. Magrou 3 and others4 recognized the bacterial origin of the process and believed Staphylococcus aureus to be the responsible agent. The first case of bacterial pseudomycosis in a human was reported by Opie5 in 1913. Winslow" collected about 40 cases from medical literature and reported six cases of his own in 1959. An additional 13 cases7 have been reported since that time; 10 with visceral involvement, two with cutaneous in fection and one case of bacterial pseudomy cosis involving the tongue. This paper describes the first case of bacterial pseudomycosis of the orbit and, in addition, presents comments on the etiology, pathophysiology and prognosis of this rare condition.
VOL. 68, NO. 3
BACTERIAL PSEUDOMYCOSIS
SOS
CASE REPORT
G. H., a 50-year-old white veteran of World War II, stepped on a land mine April 12, 1945. He received penetrating wounds to the limbs and face. The right eye was severely lacerated; the left eye was traumatized and developed a cataract. The right eye was initially repaired but phthisis bulbi soon occurred, requiring enucleation on July 12, 1945. Roentgenograms of the sinuses and orbital bones taken preoperatively showed no foreign bod ies. A 16-mm sphere of bone was used as the im plant. During the ensuing years the patient's socket pro duced excessive amounts of mucus and required cleansing two to three times a day. The discharge became heavy, foul and purulent in March, 1968. The patient was admitted to the Veterans Adminis tration Hospital, Ann Arbor, Michigan, on May 13, 1968, for the removal of the old implant. The find ings at this time were an exposed implant and pu rulent drainage in the right orbit (fig. 1). Cultures of the purulent material showed the presence of coagulase-positive Staphylococcus aureus and diphtheroid bacilli. On May 16, 1968, the implant was surgically re moved with great difficulty and was found to be about one-half the expected size with a pitted, dark-brown appearance. A heavy covering of scar tissue surrounded the implant except on the anterior surface where there was an open sinus (fig. 2). The operative cavity was packed open with iodoform gauze. Special fungus cultures were obtained and incubated anerobically and aerobically. No fungi were grown after six weeks of incubation Prior to the surgical removal of the implant, the patient received two intramuscular injections of procain penicillin, 600,000 units each ; this dose was continued postoperatively for three days. In addi tion, the patient received 500 mg staphcillin orally every six hours following the operative procedure. The operative wound was treated with a solution of Neosporin® four times per day. The postoperative course was uneventful, with rapid filling of the space by healthy granulation tis sue (fig. 3). There was complete cessation of all discharge by the time the patient left the hospital
Fig. 1 (Kallet, McKenzie and Johnson). Pre operative appearance, right cul-de-sac, showing gran ulation tissue and purulent discharge.
Fig. 2 (Kallet, McKenzie and Johnson). Gross appearance of the specimen including the central degenerated bone sphere and surrounding granulation tissue.
Fig. 3 (Kallet, McKenzie and Johnson). Post operative appearance, right cul-de-sac, showing com plete healing. on June 3, 1968. One month following operation, he had a clean cul-de-sac with no visible drainage. PATHOLOGIC FINDINGS
Following routine processing, microscopic sections of the surgical material were stained with hematoxylin-eosin, methenamine silver, periodic-acid-Schiff stain and the Brown and Breen modified-Gram stain. The specimen consisted of fragments of dead bone, discol ored by hemosiderin pigment, with granula tion tissue containing acute and chronic in flammatory infiltrates. Embedded in the granulation tissue were granules with par tially basophilic centers surrounded by irreg ular eosinophilic rims showing irregular knobby projections (fig. 4 ) . Examination under high power magnification (X400) and oil immersion lens ( X 1,000) showed
506
AMERICAN JOURNAL OF OPHTHALMOLOGY
SEPTEMBER, 1969
Schiff (PAS) stain showed the granules to be PAS-positive. No fungi were seen in the PAS or methenamine-silver stains. DISCUSSION
Fig. 4 (Kallet, McKenzie and Johnson). Inflam matory granulation tissue containing numerous fun guslike grains. (Hematoxylin-eosin, Xl25.) that these grains were composed of clusters of cocciform and rod-shaped bacteria (fig. 5). The Brown-Breen modified-Gram stain showed the best morphologic detail of the bacteria and, in addition, identified the cocci present as gram-positive. The periodic-acid-
Fig. 5. (Kallet, McKenzie and Johnson). Numer ous cocciform and rod-shaped bacteria embedded in amorphous debris. (Brown-Breen modified-grnm stain, X625.)
Bacterial pseudomycosis is only one of a group of infections characterized microscop ically by the presence of granules. These granular infections can be differentiated ac cording to the etiologic agents6: (1) higher fungi with broad hyphae in mycetoma ; (2) filamentous fungi in actinomycosis and nocardiosis ; (3) bacteria in bacterial pseudomycosis. Infections of this group mimic each other closely both grossly and microscopi cally and errors in differential diagnosis are common.6 The importance of correct diagnosis is ob vious when one considers the prolonged ef forts necessary in the treatment of fungus disease compared to the relatively simple and safe treatment of bacterial pseudomycosis. Magrou3 first recognized the bacterial etiology of this disease and strongly impli cated Staphylococcus aureus as the specific infective agent. Since that time, numerous well-documented studies have shown that other bacteria7 may also cause this unique microscopic lesion. These include staphylococci, streptococci, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Actinobacillis lignieresii. Most investigators have commented upon the hyaline mass which forms around the microorganism at the periphery of the gran ules. It seems most likely that this hyalinized material is not a special morphologic form of the causative microorganism but is instead a product of the interaction between the host tissue or host plasma factors and the offend ing agent. The resultant histologie similarity may be an expression of similar host re sponse to those common cytoplasmic anti gens present in many species of bacteria and simple fungi.8 Botryomycosis in humans falls into two main groups : integumentary with or without muscular and skeletal involvement, and pri-
VOL. 68, NO. 3
507
BACTERIAL PSEUDOMYCOSIS
mary visceral involvement. The integumen tary form may involve underlying muscle and bone, usually involves exposed areas of skin and is occasionally associated with un derlying osteomyelitis or foreign-body reac tion. Our case was associated with a foreign body (bone implant) and a chronic draining sinus. The visceral form of the disease is most commonly seen in liver, lungs and kid neys of usually, but not exlusively, debili tated individuals. Prolonged chronic inflam mation seems to be the most common factor. When bacterial pseudomycosis is sus pected in a chronic draining wound, typical granules may be found in the purulent dis charge from the draining sinuses. As with fungal grains, the bacterial granules can be isolated by carefully washing the specimen with a saline solution. To obtain material for culture, draining sinuses should be packed aseptically with a sterile gauze wick which can be retained over night and submitted in a sterile container the following morning. All specimens should be cultured for bacte ria and fungi on appropriate media. TREATMENT
The treatment of choice9 is simple exci sion of the draining sinus or granulomatous lesion and appropriate antibacterial therapy. Chronic infections such as osteomyelitis or any conditions enhancing chronicity (such as foreign body) have been noted in several of the reported cases. It is therefore important to remove any bony sequestra or foreign bodies. Our patient responded well to this therapy.
SUMMARY
Bacteria pseudomycosis is a chronic gran ulomatous and suppurative bacterial inflam mation in which bacteria cause funguslike grains or granules within a suppurative foci. The left eye of a 50-year-old white man was enucleated in 1945 and a sphere of bone im planted. The sphere was removed 23 years later because of chronic drainage from the right orbit. Funguslike grains were seen in microscopic sections of the removed mate rial. Cultures and special stains proved these to be staphylococcic and not fungal in origin. The importance of the recognition of this disease is emphasized; simple treatment is available for bacteria pseudomycosis as com pared to the prolonged treatment of mycotic disease with which it may be confused. REFERENCES
1. Bollinger, O. : Mycosis der lunge beim Pferde. Virchow Arch. Path. Anat. 49 :S83, 1870. 2. Rivolta, S. : Del micelio e delle varietà e specie di discomiceti patogeni. G. Anat. Fisiol. Pat. Ani mali 16:181, 1884. 3. Magrou, J. : Les formes actinomycotiques de staphylocoque. Ann. Inst. Pasteur 33 :344, 1919. 4. Kansky, A.: Botryomycosis. Acta Dermatovener. 44:369, 1964. 5. Opie, E. L. : Human botryomycosis of the liver. Arch. Int. Med. 11:425, 1913. 6. Winslow, D. J. : Botryomycosis. Am. J. Path. 35:153, 1959. 7. Small, I. A. and Kobernich, S. : Botryomycosis of the tongue. Oral Surg. 24:503, 1967. 8. Katznelsen, D., Vawter, G. F., Foley, G. E. and Shwachman, H. : Botryomycosis, a complica tion in cystic fibrosis. J. Ped. 65 :525, 1964. 9. Greenblatt, M., Heredia, R., Rubenstein, L. and Alpert, S. : Bacterial pseudomycosis ("botry omycosis"). Am. J. Clin. Path. 41:188, 1964.
AMERICAN JOURNAL OF OPHTHALMOLOGY
posterior subcapsular zone, with or without vacuoles, and 29 were free of such changes. The presence of lens changes was correlated with the known duration of disease and du ration of therapy with the two major chemotherapeutic agents utilized, Myleran and dibromomannitol. A possible role of these chemotherapeutic drugs in the production of human lens changes was suggested, although effects of the leukemic process on the lens could not be ruled out. ACKNOWLEDGMENTS
The suggestions of Drs. Ludwig von Sallmann and Paul Carbone are gratefully acknowledged. REFERENCES
1. Galton, D. A. G. : Myleran in chronic myeloid leukemia: Results of treatment. Lancet 1:208, 1953. 2. Casazza, A. R., Cahn, E. L. and Carbone, P. P. : Preliminary studies with dibromomannitol (NSC94100) in patients with chronic myelogenous leu kemia. Cancer Chemother. Rep. 51:91, 1967.
SEPTEMBER, 1969
3. Sallmann, L. von : The lens epithelium in the pathogenesis of cataract: The XIII Edward Jack son Memorial Lecture. Am. J. Ophth. 44:159, 1957. 4. Grimes, P., von Sallmann, L. and Frichette, A. : Influence of Myleran on cell proliferation in the lens epithelium. Invest. Ophth. 3:566, 1964. 5. Grimes, P. and von Sallmann, L. : Interference with cell proliferation and induction of polyploidy in rat lens epithelium during prolonged Myleran treatment. Exp. Cell Res. 42:265, 1966. 6. Light, A. E. : Additional observations on the effects of busulfan on cataract formation, duration of anesthesia, and reproduction in rats. Toxic. Appi. Pharmacol. 10:459, 1967. 7. Sallmann, L. von and Grimes, P. : Some effects of anticancer drugs on cell proliferation in the eye : An experimental study. Ophthalmologica Addit. 151:917, 1966. 8. Huguley, C. M. et al : Comparison of 6-mercaptopurine and busulfan in chronic granulocytic leukemia. Blood 21:89,1963. 9. Borgeson, E. J. and Wagener, H. P.: Changes in the eye in leukemia. Am. J. Med. Sci. 177:663, 1929. 10. Allen, R. A. and Straatsma, B. R.: Ocular involvement in leukemia and allied disorders. Arch. Ophth. 66:490, 1961.
BACTERIAL PSEUDOMYCOSIS O F T H E ORBIT HENRY A. KALLET, M.D.,
K E I T H S. MCKENZIE, M.D.,
AND FRANK D. JOHNSON,
M.D.
Ann Arbor, Michigan
Bacterial pseudomycosis is a chronic granulomatous and suppurative bacterial in flammation of the skin and subcutaneous tis sues or, more rarely, of soft tissue or vis cera, in which the specific feature is the presence of funguslike grains or granules within suppurative foci. These granules con tain nonbranching bacteria enclosed in a hyaline matrix and closely mimic those fun gal grains seen in actinomycosis, nocardiosis or mycetoma. The lesion was first described by Bollinger1 in 1870. In 1884 Rivolta2 encoun tered the characteristic grains in pus obFrom the Departments of Pathology and Oph thalmology, The University of Michigan Medical Center and Veterans Administration Hospital. Reprint requests to Henry A. Kallet, M.D., De partment of Pathology, 1335 East Catherine Street, Ann Arbor, Michigan 48104.
tained from infected castration wounds in horses. Believed to be fungal in origin, the infection was called botryomycosis. Magrou 3 and others4 recognized the bacterial origin of the process and believed Staphylococcus aureus to be the responsible agent. The first case of bacterial pseudomycosis in a human was reported by Opie5 in 1913. Winslow" collected about 40 cases from medical literature and reported six cases of his own in 1959. An additional 13 cases7 have been reported since that time; 10 with visceral involvement, two with cutaneous in fection and one case of bacterial pseudomy cosis involving the tongue. This paper describes the first case of bacterial pseudomycosis of the orbit and, in addition, presents comments on the etiology, pathophysiology and prognosis of this rare condition.
VOL. 68, NO. 3
BACTERIAL PSEUDOMYCOSIS
SOS
CASE REPORT
G. H., a 50-year-old white veteran of World War II, stepped on a land mine April 12, 1945. He received penetrating wounds to the limbs and face. The right eye was severely lacerated; the left eye was traumatized and developed a cataract. The right eye was initially repaired but phthisis bulbi soon occurred, requiring enucleation on July 12, 1945. Roentgenograms of the sinuses and orbital bones taken preoperatively showed no foreign bod ies. A 16-mm sphere of bone was used as the im plant. During the ensuing years the patient's socket pro duced excessive amounts of mucus and required cleansing two to three times a day. The discharge became heavy, foul and purulent in March, 1968. The patient was admitted to the Veterans Adminis tration Hospital, Ann Arbor, Michigan, on May 13, 1968, for the removal of the old implant. The find ings at this time were an exposed implant and pu rulent drainage in the right orbit (fig. 1). Cultures of the purulent material showed the presence of coagulase-positive Staphylococcus aureus and diphtheroid bacilli. On May 16, 1968, the implant was surgically re moved with great difficulty and was found to be about one-half the expected size with a pitted, dark-brown appearance. A heavy covering of scar tissue surrounded the implant except on the anterior surface where there was an open sinus (fig. 2). The operative cavity was packed open with iodoform gauze. Special fungus cultures were obtained and incubated anerobically and aerobically. No fungi were grown after six weeks of incubation Prior to the surgical removal of the implant, the patient received two intramuscular injections of procain penicillin, 600,000 units each ; this dose was continued postoperatively for three days. In addi tion, the patient received 500 mg staphcillin orally every six hours following the operative procedure. The operative wound was treated with a solution of Neosporin® four times per day. The postoperative course was uneventful, with rapid filling of the space by healthy granulation tis sue (fig. 3). There was complete cessation of all discharge by the time the patient left the hospital
Fig. 1 (Kallet, McKenzie and Johnson). Pre operative appearance, right cul-de-sac, showing gran ulation tissue and purulent discharge.
Fig. 2 (Kallet, McKenzie and Johnson). Gross appearance of the specimen including the central degenerated bone sphere and surrounding granulation tissue.
Fig. 3 (Kallet, McKenzie and Johnson). Post operative appearance, right cul-de-sac, showing com plete healing. on June 3, 1968. One month following operation, he had a clean cul-de-sac with no visible drainage. PATHOLOGIC FINDINGS
Following routine processing, microscopic sections of the surgical material were stained with hematoxylin-eosin, methenamine silver, periodic-acid-Schiff stain and the Brown and Breen modified-Gram stain. The specimen consisted of fragments of dead bone, discol ored by hemosiderin pigment, with granula tion tissue containing acute and chronic in flammatory infiltrates. Embedded in the granulation tissue were granules with par tially basophilic centers surrounded by irreg ular eosinophilic rims showing irregular knobby projections (fig. 4 ) . Examination under high power magnification (X400) and oil immersion lens ( X 1,000) showed
506
AMERICAN JOURNAL OF OPHTHALMOLOGY
SEPTEMBER, 1969
Schiff (PAS) stain showed the granules to be PAS-positive. No fungi were seen in the PAS or methenamine-silver stains. DISCUSSION
Fig. 4 (Kallet, McKenzie and Johnson). Inflam matory granulation tissue containing numerous fun guslike grains. (Hematoxylin-eosin, Xl25.) that these grains were composed of clusters of cocciform and rod-shaped bacteria (fig. 5). The Brown-Breen modified-Gram stain showed the best morphologic detail of the bacteria and, in addition, identified the cocci present as gram-positive. The periodic-acid-
Fig. 5. (Kallet, McKenzie and Johnson). Numer ous cocciform and rod-shaped bacteria embedded in amorphous debris. (Brown-Breen modified-grnm stain, X625.)
Bacterial pseudomycosis is only one of a group of infections characterized microscop ically by the presence of granules. These granular infections can be differentiated ac cording to the etiologic agents6: (1) higher fungi with broad hyphae in mycetoma ; (2) filamentous fungi in actinomycosis and nocardiosis ; (3) bacteria in bacterial pseudomycosis. Infections of this group mimic each other closely both grossly and microscopi cally and errors in differential diagnosis are common.6 The importance of correct diagnosis is ob vious when one considers the prolonged ef forts necessary in the treatment of fungus disease compared to the relatively simple and safe treatment of bacterial pseudomycosis. Magrou3 first recognized the bacterial etiology of this disease and strongly impli cated Staphylococcus aureus as the specific infective agent. Since that time, numerous well-documented studies have shown that other bacteria7 may also cause this unique microscopic lesion. These include staphylococci, streptococci, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Actinobacillis lignieresii. Most investigators have commented upon the hyaline mass which forms around the microorganism at the periphery of the gran ules. It seems most likely that this hyalinized material is not a special morphologic form of the causative microorganism but is instead a product of the interaction between the host tissue or host plasma factors and the offend ing agent. The resultant histologie similarity may be an expression of similar host re sponse to those common cytoplasmic anti gens present in many species of bacteria and simple fungi.8 Botryomycosis in humans falls into two main groups : integumentary with or without muscular and skeletal involvement, and pri-
VOL. 68, NO. 3
507
BACTERIAL PSEUDOMYCOSIS
mary visceral involvement. The integumen tary form may involve underlying muscle and bone, usually involves exposed areas of skin and is occasionally associated with un derlying osteomyelitis or foreign-body reac tion. Our case was associated with a foreign body (bone implant) and a chronic draining sinus. The visceral form of the disease is most commonly seen in liver, lungs and kid neys of usually, but not exlusively, debili tated individuals. Prolonged chronic inflam mation seems to be the most common factor. When bacterial pseudomycosis is sus pected in a chronic draining wound, typical granules may be found in the purulent dis charge from the draining sinuses. As with fungal grains, the bacterial granules can be isolated by carefully washing the specimen with a saline solution. To obtain material for culture, draining sinuses should be packed aseptically with a sterile gauze wick which can be retained over night and submitted in a sterile container the following morning. All specimens should be cultured for bacte ria and fungi on appropriate media. TREATMENT
The treatment of choice9 is simple exci sion of the draining sinus or granulomatous lesion and appropriate antibacterial therapy. Chronic infections such as osteomyelitis or any conditions enhancing chronicity (such as foreign body) have been noted in several of the reported cases. It is therefore important to remove any bony sequestra or foreign bodies. Our patient responded well to this therapy.
SUMMARY
Bacteria pseudomycosis is a chronic gran ulomatous and suppurative bacterial inflam mation in which bacteria cause funguslike grains or granules within a suppurative foci. The left eye of a 50-year-old white man was enucleated in 1945 and a sphere of bone im planted. The sphere was removed 23 years later because of chronic drainage from the right orbit. Funguslike grains were seen in microscopic sections of the removed mate rial. Cultures and special stains proved these to be staphylococcic and not fungal in origin. The importance of the recognition of this disease is emphasized; simple treatment is available for bacteria pseudomycosis as com pared to the prolonged treatment of mycotic disease with which it may be confused. REFERENCES
1. Bollinger, O. : Mycosis der lunge beim Pferde. Virchow Arch. Path. Anat. 49 :S83, 1870. 2. Rivolta, S. : Del micelio e delle varietà e specie di discomiceti patogeni. G. Anat. Fisiol. Pat. Ani mali 16:181, 1884. 3. Magrou, J. : Les formes actinomycotiques de staphylocoque. Ann. Inst. Pasteur 33 :344, 1919. 4. Kansky, A.: Botryomycosis. Acta Dermatovener. 44:369, 1964. 5. Opie, E. L. : Human botryomycosis of the liver. Arch. Int. Med. 11:425, 1913. 6. Winslow, D. J. : Botryomycosis. Am. J. Path. 35:153, 1959. 7. Small, I. A. and Kobernich, S. : Botryomycosis of the tongue. Oral Surg. 24:503, 1967. 8. Katznelsen, D., Vawter, G. F., Foley, G. E. and Shwachman, H. : Botryomycosis, a complica tion in cystic fibrosis. J. Ped. 65 :525, 1964. 9. Greenblatt, M., Heredia, R., Rubenstein, L. and Alpert, S. : Bacterial pseudomycosis ("botry omycosis"). Am. J. Clin. Path. 41:188, 1964.