Eur. J. Epidemiol. 0392-2990
EUROPEAN
Vol. 8, No. 3
JOURNAL
May 1992, p. 383-386
OF
EPIDEMIOLOGY
PHAEOHYPHOMYCOSIS CAUSED BY BIPOLARIS SPICIFERA: AN INFORMATIVE CASE M.R. McGINNIS a, G. CAMPBELL, W.K. GOURLEY and H.L. LUCIA Department o f Pathology - University o f Texas Medical Branch - Galveston - TX 77555.
Keywords: Phaeohyphomycosis - Bipolaris spicifera - Allergic sinusitis - Brain infection A case of phaeohyphomycosis caused by Bipolaris spicifera involving the brain and sinuses is presented. The patient survived following surgery and ketoconazole therapy, which successfully treated both the sinus and the brain infections.
INTRODUCTION
There has been a recent surge of interest in the study of human infection caused by the dematiaceous fungi. Dematiaceous fungi can assume several different morphological forms in human tissue, as well as cause chronic infections which ultimately become life-threatening. With closer study, there has been a re-definition of both the taxonomic status of several of the medically important black fungi and the clinical nomenclature used to describe the diseases they cause. We have recently provided care of a patient who had a long term sinus infection caused by one of the dematiaceous fungi, Bipolaris spicifera, who developed metastatic brain abscesses and allergic sinusitis. We are presenting this case as an opportunity to discuss the importance of these fungi.
Clinical History This 26 year old black female from northeast Texas was referred to University of Texas Medical Branch at Galveston (UTMB) for treatment of a left brain mass. At the age of 19 she had been admitted to another hospital with the diagnosis of meningitis. CT scan revealed a right occipital lobe brain lesion. At 1 Corresponding author.
383
that time she had decreased visual acuity in the left eye, left facial weakness, and left V th cranial nerve palsy. Sinus roentgenologic examination showed a normal sella turcica and opacification of the sphenoid sinus. Cerebral angiogram at that time suggested a mycotic aneurysm of the occipital branch of the right posterior cerebral artery. Lumbar puncture and examination of the cerebrospinal fluid revealed elevated protein, decreased glucose and leukocytosis with predominantly polymorphonuclear leukocytes, but no organisms were isolated. She was treated with penicillin, chloramphenicol, isoniazid, ethambutol, rifampin, and 510 mg. of amphotericin B. She was referred to UTMB after one month of therapy, where she underwent a right occipital craniotomy with excision of abnormal cortical tissue, which was described as "milky, yellowish tissue". She was then treated with nafcillin. She developed basilar meningitis with hydrocephalus, and a VP shunt was placed. Myelogram at this time noted arachnoid scarring at C2 - C3, and T2 - T3. She was finally discharged in an improved condition. The cranial nerve palsies improved, but the visual defect remained. She remained well for six years. Then she began to experience headaches associated with nausea. A C T scan demonstrated a new mass, and the patient was referred to UTMB for treatment. On admission, the
McGinnis M.R. et al.
patient was alert, fully oriented, and without fever. She had anisocoria, with a Marcus Gunn pupillary response to light. She had faint light perception of the left eye, with left optic atrophy. The right eye was normal. Cranial nerves V, VII and XII appeared intact. She had no motor or sensory defects. Her gait was wide-based, veering to the right, with poor tandem walking. She had moderate dysmetria of the left upper extremity. Laboratory examination on admission was unremarkable. CT scan noted a left sphenoid wing mass with a large amount of associated edema and mild midline shift, and right occipital encephalomalacia. Angiogram showed the mass to be avascular. She was taken to surgery, and a left temporal mass was biopsied, and sent for histology and microbial culture. Pure colonies of Bipolaris spicifera grew on mold inhibitory agar incubated at 30° C. The patient was begun on combined amphotericin B and ketaconazole (400 mg/ day) therapy. Although she did not report nasal sinus symptoms, a sinus examination revealed opacity of the sphenoid, left frontal and left maxillary sinuses. Erosion of the floor of the pituitary fossa was also noted. After one month of antifungal therapy, she was operated on, and a left external ethmoidectomy and left maxillary antrotomy were performed. No organisms were recovered from the specimens submitted for fungal culture. One month later, she returned to the operating room for stripping of the mucosa of the left maxillary and ethmoid sinuses. She continued on antifungal therapy for a total of three months ofketaconazole, 400 mg/day, and 3020 mg of amphotericin B. She was discharged on dilantin. One year later she returned for follow-up, and examination. Her visual examination noted no light perception on the left, and a greatly constricted visual field on the right. The CT scan was unchanged. She was discharged from follow-up.
Histopathologic Findings Tissue removed at both surgical procedures from the nasal sinuses had a similar histologic appearance. In
Eur. J. Epidemiol.
hematoxylin and eosin stained sections, the strips of respiratory mucosa were focally thickened by broad zones of dense fibrosis with few lymphocytes and plasma cells. There was no ulceration nor necrosis. Scattered throughout the fibrotic areas were clusters of small granulomata that had cores of vacuolated histiocytes surrounded by targetoid rims of concentric hyalinized collagen fibers. The centers of the granulomata contained pleomorphic oval cells (average diameter 8 lam, range 4-14 lain) and hyphae (average width 4 lam, range 2-7 pm) containing swollen cells. The Fontana-Masson stain for melanin demonstrated that the fungal cells contained melanin. No vascular invasion by the fungus was seen, but some of the granulomata had small blood vessels in their centers. The first brain biopsy, performed in 1979, consisted of brain tissue and leptomeninges from the right occipital lobe. Hematoxylin and eosin-stained sections demonstrated coagulative necrosis in some areas. In surrounding parenchyma, neuronal necrosis, mild gliosis and fibrosis, macrophage reaction and capillary and endothelial proliferation were present. The leptomeninges contained moderate numbers of primarily chronic inflammatory cells, hemorrhage and granulation tissue reaction. The overall picture was one of an early abscess formation without capsule formation. No bacterial nor fungal organisms were seen. During the present hospitalization, two biopsy specimens were obtained. The first was an open biopsy of the left temporal lobe, from which a significant amount of tissue was resected and submitted for examination. Intermixed with areas of hemorrhage and necrosis were areas with chronic and granulomatous inflammation in both perivascular and parenchymal locations. Large multinucleated giant cells were especially prominent in the parenchyma (Fig. 1A). In sections stained by Gomori's methenamine-silver (GMS) stain (Fig. 1B) and Fontana-Masson stain for melanin, septate hyphae of
Figure 1. - Fungai lesions in brain tissue. A. Langhans' - type giant cells containing swollen non-staining fungal ceils (center). Hematoxylin and Eosin stain, X120. B. Silver-stainedhyphae averaging 8 larnin diameter (right), and swollenround-to-ovalfungai cells (center and left), GMS stain, X120. 384
Phaeohyphomycosis caused by B. spicifera
VoL 8, 1992
variable diameter with occasional large, swollen cells were best demonstrated by GMS stain. The FontanaMasson stain demonstrated that melanin was present in the cell walls of the fungus in tissue. The second biopsy, obtained 17 days later, was an aspiration specimen, consisting of numerous tiny fragments of tissue. This tissue had extensive hemorrhage, vascular proliferation, and macrophage infiltration, but only mild chronic inflammation. Hyphal elements similar to those seen in the previous biopsy were also demonstrated in this material.
DISCUSSION
During the past several years, opportunistic infections caused by species of Bipolaris and Exserohilum have been described under various names, especially Drechslera and Helminthosporium spp. (10). Originally, these fungi were classified as species of Helminthosporium. As our understanding of conidiogenesis improved, it became clear that these fungi represented several different genera. It is now realized that Bipolaris, Exserohilum, Drechslera, and Helminthosporium are distinct genera, and that species of Bipolaris and Exserohilum account for nearly all of the recorded pathogens in this group of fungi. A single case caused by D. biseptata has been reported. There are four types of fungal infections of the paranasal sinuses: 1) acute infection of the mucosa with tissue necrosis, vascular invasion, and scan inflammation in a diabetic or immunodeficient host; 2) chronic colonization of the sinus cavity with formation of a fungus "ball", no tissue invasion, and an association with obstruction, dental disease, or foreign body; 3) chronic colonization of the lumen with massive mucus and eosinophilic leukocyte exudation, no tissue invasion, and an association with allergies or asthma (allergic fungal sinusitis); and 4) chronic infection of the mucosa, with a fibrosing granulomatous inflammatory host reaction, endemic in the dry environment of Northern Africa (11, 13-15). Our patient had the last type of infection with a rather indolent spread, in contrast to the rapidly lifethreatening cerebral extension of the first type and the less serious pressure effects of the second and third types. Allergic sinusitis involving noninvasive Bipolaris colonization is an example of disease due solely to a hypersensitivity response to an inhaled fungus that non-allergic individuals would expel without consequence (7). Fungoma, or fungus ball, is a unique condition in which the etiologic agent grows as an undifferentiated hyphal mass in a cavity such as the sinuses. Occasionally, fungus balls will exhibit concentric zones of, growth. When the dematiaceous fungi actually invade tissue, the characteristic forms of these fungi include granules, hyphae of various sizes and shapes, and sclerotic bodies. Based upon these histopathologic appearances, mycetoma (9),
phaeohyphomycosis, and chromoblastomycosis (2, 5, 8), respectively are the associated disease forms. These entities are a continuum of infections that are distinguished from one another by their clinical presentation, pathology, and to a lesser degree the taxonomy of the etiologic agents. Although fungal infections of the brain and meninges are not uncommon, especially in immunocompromised individuals, cerebral infections caused by Bipolaris species are rare regardless of the degree of immunocompetence. The first case was reported by Fuste, et al. in 1973 (6). This case involved a fatal meningoencephalitis in a 31 year old female, who was found at autopsy to have a previously unsuspected well-differentiated lymphoma. The causative agent was identified as Bipolaris hawaiiensis. A second report of granulomatous encephalitis caused by this organism, occurring in an immunocompetent 18 year old mate, which was published in 1986 by Morton, et al. (12). This patient was successfully treated by amphotericin B and 5-fluorocytosine. Three previous culture-confn-med reports of cerebral infection by B. spicifera have appeared in the literature. The first, which appeared in 1981, occurred in a 21 year old immunocompetent female with no known underlying disease (16). She was also treated with amphotericin B and 5-fluorocytosine. The second, reported in 1986, involved meningoencephalitis complicating compound skull fractures due to open head trauma (3). This patient, a 21 year old immunocompetent female, died 28 days after her injury. The third patient, also reported in 1986, was a 49 year old female who had a history of bilateral mastectomies, followed by radiation and chemotherapy, for breast carcinoma. She developed meningoencephalitis and died (1). The first brain lesion in our patient, which was observed when she was 19, was not conclusively proven to be caused by the fungus that caused the second brain lesion and the sinus infection. At the time of original hospitalization, no etiologic agent was identified either by culture or by histologic examination. However, the presence of sinus involvement by x-ray, the histologic appearance of the brain tissue, and the presumed response to therapy suggests that episode represents a similar process as the later one. The second episode clearly represents the simultaneous infection of sinuses and brain tissue. Because the same fungus was isolated from the sinuses and brain infection, the relationship of the two infectious processes is of interest. There was no evidence to suggest that the infection of the brain was caused by direct extension of B. spicifera from the sinuses. Yet, the recovery of the same fungus from the sinuses and brain suggests a cause in common. We postulate that the fungus reached the brain from the chronic sinus infection by hematogenous spread. In this case, the agent was a pigmented fungus and the host responded with the same partially effective granulomatous inflammation and fibrosis that is frequently seen in chronic cutaneous
385
McGinnis M.R. et aL
Eur. J. Epidemiot.
phaeohyphomycosis caused by Bipolaris and Exserohilum species (4). Additional investigations of the biology of pigmented fungi and the human immunologic response are needed to determine whether it is a property of a particular isolate, or a peculiar subtle host immune aberration, or both, that results in the incomplete containment without eradication of the organism, as was the case in our patient.
7.
Gourley D.S., Whisman B.A., Jorgensen N.L., Martin M.E. and Reid M.J. (1990): Allergic Bipolaris sinusitis: Clinical and immunopathologic characteristics - J. Allergy Clin. Immunol. 85: 583-591.
8. McGinnis M.R. (1983): Chromoblastomycosis and phaeohyphomycosis: New concepts, diagnosis, and mycology - J. Am. Acad. Dermatol. 8: 1-16. 9. McGinnis M.R. and Fader R.C. (1988): Mycetoma: A contemporary concept - Clin. Infect. Dis. 2: 939-954.
Acknowledgements
The senior author wishes to express his personal appreciation to Dr. Libero Ajello for his friendship, support and guidance. REFERENCES
1. Adam R.D., Paquin M.L., Petersen E.A., Saubolle M.A., Rinaldi M.G., Corcoran J.G., Galgiani J.N. and Sobonya R.E. (1986): Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature - Medicine 65: 203-217. 2. Ajello L., Georg L.K., Steigbigel R.T. and Wang C.J.K. (1974): A case of phaeohyphomycosis caused by a new species of Phialophora - Mycologia 66: 490-498. 3. Biggs P.J., Allen R.L., Powers J.M. and Holley H.P. (1986): Phaeohyphomycosis complicating compound skull fracture - Surg. Neurol. 25: 393-396. 4. Chandler ElF. and Watts J.C. (1987): Pathologic Diagnosis of Fungal Infections - American Society of Clinical Pathology Press - Chicago.
10. McGinnis M.R., Rinaldi M.G. and Winn R. (1986): Emerging agents of phaeohyphomycosis: Pathogenic species of Bipolaris and Exserohilum - J. Clin. Microbiol. 24: 250-259. 11. Milroy C.M., Blanshard J.D., Lucas S. and Michaels L. (1989): Aspergillosis of the nose and paranasal sinuses - J. Clin. Pathol. 42: 123-127. 12. Morton S.J., Midthun K. and Merz W. (1986): Granulomatous encephalitis caused by Bipolaris hawaiiensis- Arch. Pathol. Lab. Med. 110: 1183-1185. 13. Morgan M.A., Wilson W.R., Neel H.B. and Roberts G.D. (1984): Fungal sinusitis in healthy and immunocompromised individuals - Am. J. Clin. Pathol. 82: 597-601. 14. Veress B., Malik O.A., El Tayeb A.A., El Daoud S., Mahgoub E.S. and El Hassen A.M. (1973): Further observations on the primary paranasal Aspergillus granuloma in the Sudan - Am. J. Trop. Med. Hyg. 22: 765-772.
5. Fader R.C. and McGinnis M.R. (1988): Infections caused by dematiaceous fungi: Chromoblastomycosis and phaeohyphomycosis - Clin. Infect. Dis. 2: 925-938.
15. Waxman J.E., Spector J.G., Sale S.R. and Katzenstein A.L. (1987): Allergic Aspergillus sinusitis: Concepts in diagnosis and treatment of a new clinical entity Laryngoscope 97: 261-266.
6. Fuste F.J., Ajello L., Threlkeld R. and Henry J.E.J. (1973): Drechslera hawaiiensis: Causative agent of a fatal fungal meningo-encephalitis - Sabouraudia 11: 59-63.
16. Yoshimori R.N., Itabashi H.H. and Fujikawa D.G. (1982): Phaeohyphomycosis of brain. Granulomatous encephalitis caused by Drechslera spicifera - Am. J. Clin. Pathol. 77: 363-370.
386
EUROPEAN
Vol. 8, No. 3
JOURNAL
May 1992, p. 383-386
OF
EPIDEMIOLOGY
PHAEOHYPHOMYCOSIS CAUSED BY BIPOLARIS SPICIFERA: AN INFORMATIVE CASE M.R. McGINNIS a, G. CAMPBELL, W.K. GOURLEY and H.L. LUCIA Department o f Pathology - University o f Texas Medical Branch - Galveston - TX 77555.
Keywords: Phaeohyphomycosis - Bipolaris spicifera - Allergic sinusitis - Brain infection A case of phaeohyphomycosis caused by Bipolaris spicifera involving the brain and sinuses is presented. The patient survived following surgery and ketoconazole therapy, which successfully treated both the sinus and the brain infections.
INTRODUCTION
There has been a recent surge of interest in the study of human infection caused by the dematiaceous fungi. Dematiaceous fungi can assume several different morphological forms in human tissue, as well as cause chronic infections which ultimately become life-threatening. With closer study, there has been a re-definition of both the taxonomic status of several of the medically important black fungi and the clinical nomenclature used to describe the diseases they cause. We have recently provided care of a patient who had a long term sinus infection caused by one of the dematiaceous fungi, Bipolaris spicifera, who developed metastatic brain abscesses and allergic sinusitis. We are presenting this case as an opportunity to discuss the importance of these fungi.
Clinical History This 26 year old black female from northeast Texas was referred to University of Texas Medical Branch at Galveston (UTMB) for treatment of a left brain mass. At the age of 19 she had been admitted to another hospital with the diagnosis of meningitis. CT scan revealed a right occipital lobe brain lesion. At 1 Corresponding author.
383
that time she had decreased visual acuity in the left eye, left facial weakness, and left V th cranial nerve palsy. Sinus roentgenologic examination showed a normal sella turcica and opacification of the sphenoid sinus. Cerebral angiogram at that time suggested a mycotic aneurysm of the occipital branch of the right posterior cerebral artery. Lumbar puncture and examination of the cerebrospinal fluid revealed elevated protein, decreased glucose and leukocytosis with predominantly polymorphonuclear leukocytes, but no organisms were isolated. She was treated with penicillin, chloramphenicol, isoniazid, ethambutol, rifampin, and 510 mg. of amphotericin B. She was referred to UTMB after one month of therapy, where she underwent a right occipital craniotomy with excision of abnormal cortical tissue, which was described as "milky, yellowish tissue". She was then treated with nafcillin. She developed basilar meningitis with hydrocephalus, and a VP shunt was placed. Myelogram at this time noted arachnoid scarring at C2 - C3, and T2 - T3. She was finally discharged in an improved condition. The cranial nerve palsies improved, but the visual defect remained. She remained well for six years. Then she began to experience headaches associated with nausea. A C T scan demonstrated a new mass, and the patient was referred to UTMB for treatment. On admission, the
McGinnis M.R. et al.
patient was alert, fully oriented, and without fever. She had anisocoria, with a Marcus Gunn pupillary response to light. She had faint light perception of the left eye, with left optic atrophy. The right eye was normal. Cranial nerves V, VII and XII appeared intact. She had no motor or sensory defects. Her gait was wide-based, veering to the right, with poor tandem walking. She had moderate dysmetria of the left upper extremity. Laboratory examination on admission was unremarkable. CT scan noted a left sphenoid wing mass with a large amount of associated edema and mild midline shift, and right occipital encephalomalacia. Angiogram showed the mass to be avascular. She was taken to surgery, and a left temporal mass was biopsied, and sent for histology and microbial culture. Pure colonies of Bipolaris spicifera grew on mold inhibitory agar incubated at 30° C. The patient was begun on combined amphotericin B and ketaconazole (400 mg/ day) therapy. Although she did not report nasal sinus symptoms, a sinus examination revealed opacity of the sphenoid, left frontal and left maxillary sinuses. Erosion of the floor of the pituitary fossa was also noted. After one month of antifungal therapy, she was operated on, and a left external ethmoidectomy and left maxillary antrotomy were performed. No organisms were recovered from the specimens submitted for fungal culture. One month later, she returned to the operating room for stripping of the mucosa of the left maxillary and ethmoid sinuses. She continued on antifungal therapy for a total of three months ofketaconazole, 400 mg/day, and 3020 mg of amphotericin B. She was discharged on dilantin. One year later she returned for follow-up, and examination. Her visual examination noted no light perception on the left, and a greatly constricted visual field on the right. The CT scan was unchanged. She was discharged from follow-up.
Histopathologic Findings Tissue removed at both surgical procedures from the nasal sinuses had a similar histologic appearance. In
Eur. J. Epidemiol.
hematoxylin and eosin stained sections, the strips of respiratory mucosa were focally thickened by broad zones of dense fibrosis with few lymphocytes and plasma cells. There was no ulceration nor necrosis. Scattered throughout the fibrotic areas were clusters of small granulomata that had cores of vacuolated histiocytes surrounded by targetoid rims of concentric hyalinized collagen fibers. The centers of the granulomata contained pleomorphic oval cells (average diameter 8 lam, range 4-14 lain) and hyphae (average width 4 lam, range 2-7 pm) containing swollen cells. The Fontana-Masson stain for melanin demonstrated that the fungal cells contained melanin. No vascular invasion by the fungus was seen, but some of the granulomata had small blood vessels in their centers. The first brain biopsy, performed in 1979, consisted of brain tissue and leptomeninges from the right occipital lobe. Hematoxylin and eosin-stained sections demonstrated coagulative necrosis in some areas. In surrounding parenchyma, neuronal necrosis, mild gliosis and fibrosis, macrophage reaction and capillary and endothelial proliferation were present. The leptomeninges contained moderate numbers of primarily chronic inflammatory cells, hemorrhage and granulation tissue reaction. The overall picture was one of an early abscess formation without capsule formation. No bacterial nor fungal organisms were seen. During the present hospitalization, two biopsy specimens were obtained. The first was an open biopsy of the left temporal lobe, from which a significant amount of tissue was resected and submitted for examination. Intermixed with areas of hemorrhage and necrosis were areas with chronic and granulomatous inflammation in both perivascular and parenchymal locations. Large multinucleated giant cells were especially prominent in the parenchyma (Fig. 1A). In sections stained by Gomori's methenamine-silver (GMS) stain (Fig. 1B) and Fontana-Masson stain for melanin, septate hyphae of
Figure 1. - Fungai lesions in brain tissue. A. Langhans' - type giant cells containing swollen non-staining fungal ceils (center). Hematoxylin and Eosin stain, X120. B. Silver-stainedhyphae averaging 8 larnin diameter (right), and swollenround-to-ovalfungai cells (center and left), GMS stain, X120. 384
Phaeohyphomycosis caused by B. spicifera
VoL 8, 1992
variable diameter with occasional large, swollen cells were best demonstrated by GMS stain. The FontanaMasson stain demonstrated that melanin was present in the cell walls of the fungus in tissue. The second biopsy, obtained 17 days later, was an aspiration specimen, consisting of numerous tiny fragments of tissue. This tissue had extensive hemorrhage, vascular proliferation, and macrophage infiltration, but only mild chronic inflammation. Hyphal elements similar to those seen in the previous biopsy were also demonstrated in this material.
DISCUSSION
During the past several years, opportunistic infections caused by species of Bipolaris and Exserohilum have been described under various names, especially Drechslera and Helminthosporium spp. (10). Originally, these fungi were classified as species of Helminthosporium. As our understanding of conidiogenesis improved, it became clear that these fungi represented several different genera. It is now realized that Bipolaris, Exserohilum, Drechslera, and Helminthosporium are distinct genera, and that species of Bipolaris and Exserohilum account for nearly all of the recorded pathogens in this group of fungi. A single case caused by D. biseptata has been reported. There are four types of fungal infections of the paranasal sinuses: 1) acute infection of the mucosa with tissue necrosis, vascular invasion, and scan inflammation in a diabetic or immunodeficient host; 2) chronic colonization of the sinus cavity with formation of a fungus "ball", no tissue invasion, and an association with obstruction, dental disease, or foreign body; 3) chronic colonization of the lumen with massive mucus and eosinophilic leukocyte exudation, no tissue invasion, and an association with allergies or asthma (allergic fungal sinusitis); and 4) chronic infection of the mucosa, with a fibrosing granulomatous inflammatory host reaction, endemic in the dry environment of Northern Africa (11, 13-15). Our patient had the last type of infection with a rather indolent spread, in contrast to the rapidly lifethreatening cerebral extension of the first type and the less serious pressure effects of the second and third types. Allergic sinusitis involving noninvasive Bipolaris colonization is an example of disease due solely to a hypersensitivity response to an inhaled fungus that non-allergic individuals would expel without consequence (7). Fungoma, or fungus ball, is a unique condition in which the etiologic agent grows as an undifferentiated hyphal mass in a cavity such as the sinuses. Occasionally, fungus balls will exhibit concentric zones of, growth. When the dematiaceous fungi actually invade tissue, the characteristic forms of these fungi include granules, hyphae of various sizes and shapes, and sclerotic bodies. Based upon these histopathologic appearances, mycetoma (9),
phaeohyphomycosis, and chromoblastomycosis (2, 5, 8), respectively are the associated disease forms. These entities are a continuum of infections that are distinguished from one another by their clinical presentation, pathology, and to a lesser degree the taxonomy of the etiologic agents. Although fungal infections of the brain and meninges are not uncommon, especially in immunocompromised individuals, cerebral infections caused by Bipolaris species are rare regardless of the degree of immunocompetence. The first case was reported by Fuste, et al. in 1973 (6). This case involved a fatal meningoencephalitis in a 31 year old female, who was found at autopsy to have a previously unsuspected well-differentiated lymphoma. The causative agent was identified as Bipolaris hawaiiensis. A second report of granulomatous encephalitis caused by this organism, occurring in an immunocompetent 18 year old mate, which was published in 1986 by Morton, et al. (12). This patient was successfully treated by amphotericin B and 5-fluorocytosine. Three previous culture-confn-med reports of cerebral infection by B. spicifera have appeared in the literature. The first, which appeared in 1981, occurred in a 21 year old immunocompetent female with no known underlying disease (16). She was also treated with amphotericin B and 5-fluorocytosine. The second, reported in 1986, involved meningoencephalitis complicating compound skull fractures due to open head trauma (3). This patient, a 21 year old immunocompetent female, died 28 days after her injury. The third patient, also reported in 1986, was a 49 year old female who had a history of bilateral mastectomies, followed by radiation and chemotherapy, for breast carcinoma. She developed meningoencephalitis and died (1). The first brain lesion in our patient, which was observed when she was 19, was not conclusively proven to be caused by the fungus that caused the second brain lesion and the sinus infection. At the time of original hospitalization, no etiologic agent was identified either by culture or by histologic examination. However, the presence of sinus involvement by x-ray, the histologic appearance of the brain tissue, and the presumed response to therapy suggests that episode represents a similar process as the later one. The second episode clearly represents the simultaneous infection of sinuses and brain tissue. Because the same fungus was isolated from the sinuses and brain infection, the relationship of the two infectious processes is of interest. There was no evidence to suggest that the infection of the brain was caused by direct extension of B. spicifera from the sinuses. Yet, the recovery of the same fungus from the sinuses and brain suggests a cause in common. We postulate that the fungus reached the brain from the chronic sinus infection by hematogenous spread. In this case, the agent was a pigmented fungus and the host responded with the same partially effective granulomatous inflammation and fibrosis that is frequently seen in chronic cutaneous
385
McGinnis M.R. et aL
Eur. J. Epidemiot.
phaeohyphomycosis caused by Bipolaris and Exserohilum species (4). Additional investigations of the biology of pigmented fungi and the human immunologic response are needed to determine whether it is a property of a particular isolate, or a peculiar subtle host immune aberration, or both, that results in the incomplete containment without eradication of the organism, as was the case in our patient.
7.
Gourley D.S., Whisman B.A., Jorgensen N.L., Martin M.E. and Reid M.J. (1990): Allergic Bipolaris sinusitis: Clinical and immunopathologic characteristics - J. Allergy Clin. Immunol. 85: 583-591.
8. McGinnis M.R. (1983): Chromoblastomycosis and phaeohyphomycosis: New concepts, diagnosis, and mycology - J. Am. Acad. Dermatol. 8: 1-16. 9. McGinnis M.R. and Fader R.C. (1988): Mycetoma: A contemporary concept - Clin. Infect. Dis. 2: 939-954.
Acknowledgements
The senior author wishes to express his personal appreciation to Dr. Libero Ajello for his friendship, support and guidance. REFERENCES
1. Adam R.D., Paquin M.L., Petersen E.A., Saubolle M.A., Rinaldi M.G., Corcoran J.G., Galgiani J.N. and Sobonya R.E. (1986): Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature - Medicine 65: 203-217. 2. Ajello L., Georg L.K., Steigbigel R.T. and Wang C.J.K. (1974): A case of phaeohyphomycosis caused by a new species of Phialophora - Mycologia 66: 490-498. 3. Biggs P.J., Allen R.L., Powers J.M. and Holley H.P. (1986): Phaeohyphomycosis complicating compound skull fracture - Surg. Neurol. 25: 393-396. 4. Chandler ElF. and Watts J.C. (1987): Pathologic Diagnosis of Fungal Infections - American Society of Clinical Pathology Press - Chicago.
10. McGinnis M.R., Rinaldi M.G. and Winn R. (1986): Emerging agents of phaeohyphomycosis: Pathogenic species of Bipolaris and Exserohilum - J. Clin. Microbiol. 24: 250-259. 11. Milroy C.M., Blanshard J.D., Lucas S. and Michaels L. (1989): Aspergillosis of the nose and paranasal sinuses - J. Clin. Pathol. 42: 123-127. 12. Morton S.J., Midthun K. and Merz W. (1986): Granulomatous encephalitis caused by Bipolaris hawaiiensis- Arch. Pathol. Lab. Med. 110: 1183-1185. 13. Morgan M.A., Wilson W.R., Neel H.B. and Roberts G.D. (1984): Fungal sinusitis in healthy and immunocompromised individuals - Am. J. Clin. Pathol. 82: 597-601. 14. Veress B., Malik O.A., El Tayeb A.A., El Daoud S., Mahgoub E.S. and El Hassen A.M. (1973): Further observations on the primary paranasal Aspergillus granuloma in the Sudan - Am. J. Trop. Med. Hyg. 22: 765-772.
5. Fader R.C. and McGinnis M.R. (1988): Infections caused by dematiaceous fungi: Chromoblastomycosis and phaeohyphomycosis - Clin. Infect. Dis. 2: 925-938.
15. Waxman J.E., Spector J.G., Sale S.R. and Katzenstein A.L. (1987): Allergic Aspergillus sinusitis: Concepts in diagnosis and treatment of a new clinical entity Laryngoscope 97: 261-266.
6. Fuste F.J., Ajello L., Threlkeld R. and Henry J.E.J. (1973): Drechslera hawaiiensis: Causative agent of a fatal fungal meningo-encephalitis - Sabouraudia 11: 59-63.
16. Yoshimori R.N., Itabashi H.H. and Fujikawa D.G. (1982): Phaeohyphomycosis of brain. Granulomatous encephalitis caused by Drechslera spicifera - Am. J. Clin. Pathol. 77: 363-370.
386
