CASE REPORT * ETUDE DE CAS
Coccidioidal meningitis acquired during holidays in Arizona A*
a
Geoffrey D. Taylor, MD, FRCPC; Dennis W. Boettger, MD; Lilly J. Miedzinski, MD, FRCPC; D. Lorne J. Tyrrell, MD, PhD, FRCPC E ach year thousands of Canadians spend part or all of the winter in the southern United States. We describe three cases in which Canadians presented with coccidioidal meningitis acquired during holidays in Arizona. We also describe our experience with fluconazole, a new antifungal agent that may be a major advance in the treatment of this condition.1
Case reports Case 1 A 76-year-old white man presented with a 2-month history of anorexia, weight loss and headache. Since retirement the patient had spent each winter in Arizona. Chest x-ray films revealed bilateral hilar and mediastinal adenopathy. A biopsy specimen of the nodes revealed histologic evidence of yeast forms resembling Coccidioides immitis. He was transferred to the University of Alberta Hospitals, Edmonton, for further evaluation. Examination revealed supraclavicular adenopathy, more extensive on the right, and cachexia. Culture of sputum and a biopsy specimen of the supraclavicular nodes yielded C. immitis on several occasions. Lumbar puncture revealed a leukocyte count of 109 X 106/L, an elevated protein level and a depressed glucose level. Coccidioides antibody was detected in the cerebrospinal fluid (CSF) by means of immunodiffusion and complement fixation (titre 1:16); however, the culture results were negative. Mycobacterium tuberculosis was isolated from the supraclavicular nodes but not from any other site. Intravenous therapy with amphotericin B, 1.8 g
for 3 months, resolved the lymphadenopathy but was poorly tolerated. Another course, 1.6 g over 3 months, was started 2 months after the first one because of subsequent enlargement of the supraclavicular nodes and isolation of C. immitis from purulent material. Again, after the amphotericin B therapy was stopped the supraclavicular nodes enlarged and C. immitis was isolated. Therapy with ketoconazole, 400 mg/d, was started along with antituberculous chemotherapy. Intrathecal injections of amphotericin B were administered three times weekly under fluoroscopic guidance. The dose was 0.01 mg at first and then was increased over 2 months to 0.025 mg. Premedication with analgesics before each injection was required so that the patient could withstand the discomfort of the procedure. As the CSF leukocyte count returned to normal the frequency of injections was gradually reduced to once every 4 weeks. However, Coccidioides antibody, as detected by immunodiffusion, was still present in the CSF 1 year after initial presentation; complement-fixation testing was not repeated. Fourteen months after presentation the patient requested that the injections be stopped. He was transferred to his local hospital and given oral therapy with ketoconazole, 600 mg/d. Over the following 11/2 years he remained emotionally labile and exhibited poor memory. He denied headache. In the spring of 1989, while he was still receiving ketoconazole, drainage developed from the left axilla and supraclavicular regions, and C. immitis was again cultured. In-vitro susceptibility testing was not performed. Oral therapy with fluconazole, 400 mg/d, was begun and the ketoconazole therapy stopped. Three months later the drainage resolved; his gait
Drs. Taylor, Miedzinski and Tyrrell are with the Division of Infectious Diseases, Department of Medicine, University ofAlberta Hospitals, Edmonton. Dr. Boettger is with the Sacred Heart Hospital, McLennan, Alta.
Reprint requests to: Dr. Geoffrey D. Taylor, Rm. 2E3. 11, Walter C. Mackenzie Health Sciences Centre, University ofAlberta Hospitals, 8440-112 St., Edmonton, Alta. T6G 2B7 1388
CAN MED ASSOC J 1990; 142 (12)
and mental activity improved, and his weight increased. The patient was discharged home and continued to receive fluconazole.
Case 2 A 66-year-old white woman presented in Arizona with a 2-month history of weakness, headache and ataxia. For the previous 9 years she and her husband had spent the winters in Arizona. In 1981 malaise and rash developed during her stay there. Oral prednisone therapy was given. Abdominal discomfort, anorexia, sweating, weakness, dizziness and ataxia developed. Serum complement-fixation testing for Coccidioides antibody yielded a titre of 1:16. Coccidioidal meningitis was suspected, and she returned to Edmonton for further assessment. On examination tremulousness and mild ataxia were observed. Lumbar puncture revealed an erythrocyte count of 162 x 106/L and a leukocyte count of 126 x 106/L. Coccidioides antibody was detected by means of immunodiffusion, latex agglutination and complement fixation (titre 1:8). The patient received a total of 1.3 g of amphotericin B administered intravenously; intrathecal injections were given at a dosage similar to that in case 1. Within 3 months the leukocyte count was consistently below 10 x 106/L, and Coccidioides antibody was not found. After the injections were tapered to once every 6 weeks the CSF leukocyte count increased and antibody was detected. An increase in the frequency of the injections caused an improvement in the patient's condition. Over the following 8 years clinical relapse occurred each time the frequency decreased to less than once every 2 to 3 weeks. A trial of high-dose (800 mg/d) ketoconazole therapy without amphotericin B injections was associated with relapse. Postural hypotension gradually developed and the ataxia progressed during the later years. In February 1989 oral therapy with fluconazole, 200 mg twice daily, was started and the amphotericin B stopped. The patient remained ataxic and prone to postural hypotension. Lumbar puncture 3 months later showed a leukocyte count of 12 x 106/L, a level as good as or better than any achieved over the previous 8 years. Six months after the start of fluconazole therapy the patient's condition was clinically unchanged.
Case 3 Coccidioidal meningitis was diagnosed in a 72-year-old white man from Alberta during his stay in Arizona, where he spent his winters. He had a history of carcinoma of the prostate with metastases to bone. Three months earlier the patient had
presented with malaise and myalgia. At that time the leukocyte count had been 21.0 x 109/L, and primary coccidioidomycosis had been diagnosed. Over the subsequent weeks the symptoms of the primary fungal infection gradually lessened. Headaches, unsteady gait and confusion then developed. The CSF was examined, and the leukocyte count was 680 x 106/L. Coccidioides antibody was detected in the CSF through complement fixation (titre 1:4). Oral ketoconazole therapy and intravenous and intrathecal amphotericin B therapy were started in Arizona. An Omaya reservoir (American Hospital Supplies, Mississauga, Ont.) was inserted to facilitate the intrathecal injections. The patient was transferred to Edmonton 3 weeks after the neurologic presentation. On admission the patient was alert but vague. An intention tremor, past pointing and Romberg's sign were observed. The ketoconazole therapy was stopped. The intravenous amphotericin B therapy was eventually stopped, after a total dose of 900 mg, because of renal failure. Four weeks after the patient was transferred acute right hemiplegia and aphasia developed; the CSF leukocyte count was 38 x 106/L, but the culture results were negative. The amphotericin B injections were stopped. His condition improved, but then his level of consciousness gradually deteriorated. After amphotericin B therapy was started again, the CSF leukocyte count increased. Because amphotericin-Binduced arachnoiditis was suspected oral therapy withh fluconazole, 400 mg twice daily, was given instead. The CSF leukocyte count improved; however, his condition continued to deteriorate, and he became comatose. Four months after the initial diagnosis, in consultation with the family, all active treatment was withdrawn, and the patient died. At autopsy signs of chronic basal meningitis and multiple resolving cerebral and brain-stem infarcts were found.
Comments C. immitis is a soil fungus that infects people when spores are inhaled; thus, the risk is greatest during dry, windy seasons or when the soil is disturbed, such as during construction. Coccidioidomycosis is endemic in parts of Arizona, California,
Texas, Nevada, New Mexico and Utah and in bordering regions of northern Mexico.2 Skin testing among people residing in these areas has shown that up to one-third have been infected, although up to 60% of all infections are asymptomatic.3 Physicians should ask patients about their travel history. Clinical disease can present in various forms, from a mild, influenza-like illness to a progressive disseminated disease that may include meningitis. CAN MED ASSOC J 1990; 142 (12)
1389
Erythema nodosum or multiforme may be the only clinical manifestation.4 In patients with coccidioidal meningitis there are various abnormalities of the CSF, usually including the presence of Coccidioides antibody, as detected through complement fixation; CSF culture infrequently yields positive results. The frequency of disseminated disease in symptomatic primary infection is 1% among white people and has been found to be greater than that among dark-skinned people.5 In case 2 the corticosteroid therapy may have facilitated dissemination by causing immunosuppression. Age has not been shown to be a risk factor for coccidioidal meningitis.5 The fact that all of the patients we have described were over 65 years of age likely reflects the population travelling to Arizona from Alberta on a regular basis rather than age-related susceptibility. If left untreated disseminated coccidioidomycosis usually causes death, especially if there is meningeal involvement. Treatment alters this outcome but, as in our cases, can be difficult and prolonged, even lifelong. Amphotericin B is the preferred drug, against which the effectiveness of other drugs is measured. In meningitis intrathecal injection is required because of poor diffusion of amphotericin B across the blood-brain barrier. Late arachnoiditis commonly occurs. The use of Omaya reservoirs is not routinely recommended, because it is associated with high rates of complications (up to 85%), mainly owing to secondary bacterial infection.5 In case 3 the cause of the neurologic deterioration and death could not be precisely determined; progressive infection, complications from the intrathecal injections or the Omaya reservoir, and unrelated vascular disease are all possibilities. High-dose oral ketoconazole therapy, although initially promising,6 has not replaced intrathecal amphotericin B therapy. In case 2 the ketoconazole therapy was unsuccessful. The duration of therapy should be determined on an individual basis; however, in practice most patients are treated for months or years and some for life. Fluconazole, a new imidazole antifungal agent, appears to be promising as an alternative for the treatment of coccidioidal meningitis.7 It has been found to be effective in vitro against C. immitis and against disseminated coccidioidomycosis in mice.8 Unlike ketoconazole fluconazole readily crosses the blood-brain barrier.9 A small uncontrolled study involving patients with chronic coccidioidal meningitis has shown that fluconazole may indeed play a useful role. ' Our experience, although limited in follow-up, supports this evidence. Nevertheless, until further studies demonstrate the long-term efficacy of fluconazole, intrathecal therapy with amphotericin B remains the treatment of choice. 1390
CAN MED ASSOC J 1990; 142 ( 12)
We thank our colleagues in the Division of Infectious Diseases who collaborated in the treatment of the patients. We also thank Pfizer Canada Inc. for providing the fluconazole.
References 1. Classen DC, Burke JP, Smith CB: Treatment of coccidioidal meningitis with fluconazole. J Infect Dis 1988; 158: 903-904 2. Drutz DH, Catanzaro A: Coccidioidomycosis. Am Rev Respir Dis 1978; 117: 559-587 3. Dodge RR, Lebowitz MD, Barbee R et al: Estimates of C. immitis infection by skin test reactivity in an endemic community. Am J Public Health 1985; 75: 863-865 4. Catanzaro A, Drutz DJ: Primary coccidioidomycosis. In Stevens DA (ed): Coccidioidomycosis: a Text, Plenum, New York, 1980: 139-144 5. Bouza E, Dreyer JS, Hewitt WL et al: Coccidioidal meningitis: an analysis of thirty-one cases and review of the literature. Medicine (Baltimore) 1981; 60: 139-172 6. Craven PC, Graybill JR, Jorgensen JH et al: High dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med 1983; 98: 160-167 7. Dismukes WE: Azole antifungal drugs: old and new. Ann Intern Med 1988; 109: 177-178 8. Graybill JR, Sunshabren J: Treatment of coccidioidal meningitis with fluconazole. J Med Vet Mycol 1986; 24: 113-119 9. Foulds G, Grennan DR, Wajszczuk C et al: Fluconazole penetration to cerebrospinal fluid in humans. J Clin Pharmacol 1988; 28: 363-366
The cure for complex legislation. Maintaining awareness of the changing rules and regulations which govern the medical profession can be a formidable task. Our Health Law Department can help. With extensive industry knowledge and experience in the legal aspects of health care, we can provide advice on all areas of health law including business, commercial and tax issues, professional complaints and all misconduct, conflict of interest and other related issues. As a client of Goodman and Carr, you'll benefit from the resources of a large firm, while receiving the individual attention of a dedicated group of lawyers who have an in-depth understanding of the legal issues involved in your practice. Contact: Tracey Tremayne-Lloyd Partner, Health Law Department
GOODMANANDC ARR BARRISTERS SOLICITORS AND
Suite 2300, 200 King Street West, Toronto, Ontario M5H 3W5 Telephone (416) 595-2300 Fax (416) 595-0567 Member of Goodman Lapointe Ferguson Toronto North York Montreal Vancouver
Coccidioidal meningitis acquired during holidays in Arizona A*
a
Geoffrey D. Taylor, MD, FRCPC; Dennis W. Boettger, MD; Lilly J. Miedzinski, MD, FRCPC; D. Lorne J. Tyrrell, MD, PhD, FRCPC E ach year thousands of Canadians spend part or all of the winter in the southern United States. We describe three cases in which Canadians presented with coccidioidal meningitis acquired during holidays in Arizona. We also describe our experience with fluconazole, a new antifungal agent that may be a major advance in the treatment of this condition.1
Case reports Case 1 A 76-year-old white man presented with a 2-month history of anorexia, weight loss and headache. Since retirement the patient had spent each winter in Arizona. Chest x-ray films revealed bilateral hilar and mediastinal adenopathy. A biopsy specimen of the nodes revealed histologic evidence of yeast forms resembling Coccidioides immitis. He was transferred to the University of Alberta Hospitals, Edmonton, for further evaluation. Examination revealed supraclavicular adenopathy, more extensive on the right, and cachexia. Culture of sputum and a biopsy specimen of the supraclavicular nodes yielded C. immitis on several occasions. Lumbar puncture revealed a leukocyte count of 109 X 106/L, an elevated protein level and a depressed glucose level. Coccidioides antibody was detected in the cerebrospinal fluid (CSF) by means of immunodiffusion and complement fixation (titre 1:16); however, the culture results were negative. Mycobacterium tuberculosis was isolated from the supraclavicular nodes but not from any other site. Intravenous therapy with amphotericin B, 1.8 g
for 3 months, resolved the lymphadenopathy but was poorly tolerated. Another course, 1.6 g over 3 months, was started 2 months after the first one because of subsequent enlargement of the supraclavicular nodes and isolation of C. immitis from purulent material. Again, after the amphotericin B therapy was stopped the supraclavicular nodes enlarged and C. immitis was isolated. Therapy with ketoconazole, 400 mg/d, was started along with antituberculous chemotherapy. Intrathecal injections of amphotericin B were administered three times weekly under fluoroscopic guidance. The dose was 0.01 mg at first and then was increased over 2 months to 0.025 mg. Premedication with analgesics before each injection was required so that the patient could withstand the discomfort of the procedure. As the CSF leukocyte count returned to normal the frequency of injections was gradually reduced to once every 4 weeks. However, Coccidioides antibody, as detected by immunodiffusion, was still present in the CSF 1 year after initial presentation; complement-fixation testing was not repeated. Fourteen months after presentation the patient requested that the injections be stopped. He was transferred to his local hospital and given oral therapy with ketoconazole, 600 mg/d. Over the following 11/2 years he remained emotionally labile and exhibited poor memory. He denied headache. In the spring of 1989, while he was still receiving ketoconazole, drainage developed from the left axilla and supraclavicular regions, and C. immitis was again cultured. In-vitro susceptibility testing was not performed. Oral therapy with fluconazole, 400 mg/d, was begun and the ketoconazole therapy stopped. Three months later the drainage resolved; his gait
Drs. Taylor, Miedzinski and Tyrrell are with the Division of Infectious Diseases, Department of Medicine, University ofAlberta Hospitals, Edmonton. Dr. Boettger is with the Sacred Heart Hospital, McLennan, Alta.
Reprint requests to: Dr. Geoffrey D. Taylor, Rm. 2E3. 11, Walter C. Mackenzie Health Sciences Centre, University ofAlberta Hospitals, 8440-112 St., Edmonton, Alta. T6G 2B7 1388
CAN MED ASSOC J 1990; 142 (12)
and mental activity improved, and his weight increased. The patient was discharged home and continued to receive fluconazole.
Case 2 A 66-year-old white woman presented in Arizona with a 2-month history of weakness, headache and ataxia. For the previous 9 years she and her husband had spent the winters in Arizona. In 1981 malaise and rash developed during her stay there. Oral prednisone therapy was given. Abdominal discomfort, anorexia, sweating, weakness, dizziness and ataxia developed. Serum complement-fixation testing for Coccidioides antibody yielded a titre of 1:16. Coccidioidal meningitis was suspected, and she returned to Edmonton for further assessment. On examination tremulousness and mild ataxia were observed. Lumbar puncture revealed an erythrocyte count of 162 x 106/L and a leukocyte count of 126 x 106/L. Coccidioides antibody was detected by means of immunodiffusion, latex agglutination and complement fixation (titre 1:8). The patient received a total of 1.3 g of amphotericin B administered intravenously; intrathecal injections were given at a dosage similar to that in case 1. Within 3 months the leukocyte count was consistently below 10 x 106/L, and Coccidioides antibody was not found. After the injections were tapered to once every 6 weeks the CSF leukocyte count increased and antibody was detected. An increase in the frequency of the injections caused an improvement in the patient's condition. Over the following 8 years clinical relapse occurred each time the frequency decreased to less than once every 2 to 3 weeks. A trial of high-dose (800 mg/d) ketoconazole therapy without amphotericin B injections was associated with relapse. Postural hypotension gradually developed and the ataxia progressed during the later years. In February 1989 oral therapy with fluconazole, 200 mg twice daily, was started and the amphotericin B stopped. The patient remained ataxic and prone to postural hypotension. Lumbar puncture 3 months later showed a leukocyte count of 12 x 106/L, a level as good as or better than any achieved over the previous 8 years. Six months after the start of fluconazole therapy the patient's condition was clinically unchanged.
Case 3 Coccidioidal meningitis was diagnosed in a 72-year-old white man from Alberta during his stay in Arizona, where he spent his winters. He had a history of carcinoma of the prostate with metastases to bone. Three months earlier the patient had
presented with malaise and myalgia. At that time the leukocyte count had been 21.0 x 109/L, and primary coccidioidomycosis had been diagnosed. Over the subsequent weeks the symptoms of the primary fungal infection gradually lessened. Headaches, unsteady gait and confusion then developed. The CSF was examined, and the leukocyte count was 680 x 106/L. Coccidioides antibody was detected in the CSF through complement fixation (titre 1:4). Oral ketoconazole therapy and intravenous and intrathecal amphotericin B therapy were started in Arizona. An Omaya reservoir (American Hospital Supplies, Mississauga, Ont.) was inserted to facilitate the intrathecal injections. The patient was transferred to Edmonton 3 weeks after the neurologic presentation. On admission the patient was alert but vague. An intention tremor, past pointing and Romberg's sign were observed. The ketoconazole therapy was stopped. The intravenous amphotericin B therapy was eventually stopped, after a total dose of 900 mg, because of renal failure. Four weeks after the patient was transferred acute right hemiplegia and aphasia developed; the CSF leukocyte count was 38 x 106/L, but the culture results were negative. The amphotericin B injections were stopped. His condition improved, but then his level of consciousness gradually deteriorated. After amphotericin B therapy was started again, the CSF leukocyte count increased. Because amphotericin-Binduced arachnoiditis was suspected oral therapy withh fluconazole, 400 mg twice daily, was given instead. The CSF leukocyte count improved; however, his condition continued to deteriorate, and he became comatose. Four months after the initial diagnosis, in consultation with the family, all active treatment was withdrawn, and the patient died. At autopsy signs of chronic basal meningitis and multiple resolving cerebral and brain-stem infarcts were found.
Comments C. immitis is a soil fungus that infects people when spores are inhaled; thus, the risk is greatest during dry, windy seasons or when the soil is disturbed, such as during construction. Coccidioidomycosis is endemic in parts of Arizona, California,
Texas, Nevada, New Mexico and Utah and in bordering regions of northern Mexico.2 Skin testing among people residing in these areas has shown that up to one-third have been infected, although up to 60% of all infections are asymptomatic.3 Physicians should ask patients about their travel history. Clinical disease can present in various forms, from a mild, influenza-like illness to a progressive disseminated disease that may include meningitis. CAN MED ASSOC J 1990; 142 (12)
1389
Erythema nodosum or multiforme may be the only clinical manifestation.4 In patients with coccidioidal meningitis there are various abnormalities of the CSF, usually including the presence of Coccidioides antibody, as detected through complement fixation; CSF culture infrequently yields positive results. The frequency of disseminated disease in symptomatic primary infection is 1% among white people and has been found to be greater than that among dark-skinned people.5 In case 2 the corticosteroid therapy may have facilitated dissemination by causing immunosuppression. Age has not been shown to be a risk factor for coccidioidal meningitis.5 The fact that all of the patients we have described were over 65 years of age likely reflects the population travelling to Arizona from Alberta on a regular basis rather than age-related susceptibility. If left untreated disseminated coccidioidomycosis usually causes death, especially if there is meningeal involvement. Treatment alters this outcome but, as in our cases, can be difficult and prolonged, even lifelong. Amphotericin B is the preferred drug, against which the effectiveness of other drugs is measured. In meningitis intrathecal injection is required because of poor diffusion of amphotericin B across the blood-brain barrier. Late arachnoiditis commonly occurs. The use of Omaya reservoirs is not routinely recommended, because it is associated with high rates of complications (up to 85%), mainly owing to secondary bacterial infection.5 In case 3 the cause of the neurologic deterioration and death could not be precisely determined; progressive infection, complications from the intrathecal injections or the Omaya reservoir, and unrelated vascular disease are all possibilities. High-dose oral ketoconazole therapy, although initially promising,6 has not replaced intrathecal amphotericin B therapy. In case 2 the ketoconazole therapy was unsuccessful. The duration of therapy should be determined on an individual basis; however, in practice most patients are treated for months or years and some for life. Fluconazole, a new imidazole antifungal agent, appears to be promising as an alternative for the treatment of coccidioidal meningitis.7 It has been found to be effective in vitro against C. immitis and against disseminated coccidioidomycosis in mice.8 Unlike ketoconazole fluconazole readily crosses the blood-brain barrier.9 A small uncontrolled study involving patients with chronic coccidioidal meningitis has shown that fluconazole may indeed play a useful role. ' Our experience, although limited in follow-up, supports this evidence. Nevertheless, until further studies demonstrate the long-term efficacy of fluconazole, intrathecal therapy with amphotericin B remains the treatment of choice. 1390
CAN MED ASSOC J 1990; 142 ( 12)
We thank our colleagues in the Division of Infectious Diseases who collaborated in the treatment of the patients. We also thank Pfizer Canada Inc. for providing the fluconazole.
References 1. Classen DC, Burke JP, Smith CB: Treatment of coccidioidal meningitis with fluconazole. J Infect Dis 1988; 158: 903-904 2. Drutz DH, Catanzaro A: Coccidioidomycosis. Am Rev Respir Dis 1978; 117: 559-587 3. Dodge RR, Lebowitz MD, Barbee R et al: Estimates of C. immitis infection by skin test reactivity in an endemic community. Am J Public Health 1985; 75: 863-865 4. Catanzaro A, Drutz DJ: Primary coccidioidomycosis. In Stevens DA (ed): Coccidioidomycosis: a Text, Plenum, New York, 1980: 139-144 5. Bouza E, Dreyer JS, Hewitt WL et al: Coccidioidal meningitis: an analysis of thirty-one cases and review of the literature. Medicine (Baltimore) 1981; 60: 139-172 6. Craven PC, Graybill JR, Jorgensen JH et al: High dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med 1983; 98: 160-167 7. Dismukes WE: Azole antifungal drugs: old and new. Ann Intern Med 1988; 109: 177-178 8. Graybill JR, Sunshabren J: Treatment of coccidioidal meningitis with fluconazole. J Med Vet Mycol 1986; 24: 113-119 9. Foulds G, Grennan DR, Wajszczuk C et al: Fluconazole penetration to cerebrospinal fluid in humans. J Clin Pharmacol 1988; 28: 363-366
The cure for complex legislation. Maintaining awareness of the changing rules and regulations which govern the medical profession can be a formidable task. Our Health Law Department can help. With extensive industry knowledge and experience in the legal aspects of health care, we can provide advice on all areas of health law including business, commercial and tax issues, professional complaints and all misconduct, conflict of interest and other related issues. As a client of Goodman and Carr, you'll benefit from the resources of a large firm, while receiving the individual attention of a dedicated group of lawyers who have an in-depth understanding of the legal issues involved in your practice. Contact: Tracey Tremayne-Lloyd Partner, Health Law Department
GOODMANANDC ARR BARRISTERS SOLICITORS AND
Suite 2300, 200 King Street West, Toronto, Ontario M5H 3W5 Telephone (416) 595-2300 Fax (416) 595-0567 Member of Goodman Lapointe Ferguson Toronto North York Montreal Vancouver
