Vol. 113, May
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1975 by The Williams & Wilkins Co.
BLASTOMYCOSIS OF THE GENITOURINARY TRACT HANS-UDO EICKENBERG, MOHAMMAD AMIN
AND
ROBERT LICH, JR.
From the Section of Urology, Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky
ABSTRACT
In a retrospective study of 51 cases of systemic North American blastomycosis 11 patients were found to have genitourinary tract involvement, the prostate and e idid mis bein most commonly affected. Diagnosis was made by culture of the ungus from urine, abscess or prostate secretions, morphologic identification of the characteristic organism in urine or secretions, or histologic examination of tissue specimens. Treatment with amphotericin B reduced the mortality rate of 90 per cent to as low per cent. Long-term followup is necessary because of a relapse rate of 10 to 15 per cent.
aslU
North American blastomycosis is a systemic fungal disease caused by Blastomyces dermatitides . Gilchrist first isolated this fungus in 1894 from a skin lesion.'· 2 It is sometimes known as Gilchrist's or Chicago disease. The disease has definite geographical predilections with endemic areas centering in Ohio, the Mississippi and Missouri river valleys, and along the western shores of Lake Michigan. 3 Blastomyces dermatitides is a dimorphic fungus found in the soil, which is probably the source of infection.• It is known to affect dogs and horses but there is no evidence that these animals transmit the disease. The most common mode of acquiring the infection is inhalation, producing a primary pulmonary focus . A few cases of transmission have been reported from men with prostatic involvement to their female sexual partners. 5 • 6 At room temperature it can be grown on Sabouraud's medium into a white fluffy mold-like form. In the human body or at 37C on blood agar, it grows in its yeast-like state. It spreads by hematogenous or lymphatic routes and may disseminate to any organ in the body. Genitourinary involvement accounts for 20 to 30 per cent of all the cases of systemic blastomycosis. Rolnick and Baumrucker reviewed the literature in 1958, and since then genitourinary blastomycosis is being recognized with increasing frequency. 7 MATERIAL
North American blastomycosis has been encountered in 51 cases at the University of Louisville Affiliated Hospitals in the last 25 years . Table 1 shows the patient distribution in the Veterans Administration and Louisville General Hospitals and the incidence of genitourinary tract involve ment. Genitourinary tract involvement was eviAccepted for publication August 16, 1974. Read at annual meeting of American Urological Association, St. Louis, Missouri, May 19- 23, 1974.
dent in 11 patients, which is an incidence of approximately 21.5 per cent. Diagnoses were verified either by culture or the finding of typical organisms in the tissues. Some patients studied were reported in 1964 as part of the Veterans Administration Cooperative Study on blastomycosis. • Various parameters were analyzed. Age. The patients ranged in age from 25 to 69 years. This range coincides with the reported peak incidence at 20 to 50 years. 9 The youngest patient was a 21-month-old child who had fungus cultured from blood and bone marrow but who had no evidence of genitourinary involvement. Sex. Blastomycosis is up to 15 times more common in male than in female subjects. No female patient was found to have genitourinary involvement in the cases we studied. TABLE
1. Patient distribution with blastomycosis
Hospital
Systemic
V.A.H. L.G.H . Totals
37 14 51
Genitourinary 6 5 11
Race and residence. Eight white and 3 black patients showed involvement of the genitourinary tract. All patients were either from the city of Louisville or rural Kentucky, which ranks second highest on the list of states with incidence of North American blastomycosis.• Occupation. Complete data were not available but of 5 persons with genitourinary involvement, 4 were engaged in outdoor jobs involving exposure to soil. Dogs and horses are known to carry the disease but human infection is not believed to be acquired from this source. A recent survey revealed a higher incidence of mycotic infections in dogs from rural Kentucky as compared to urban areas. 10 This incidence may be explained by different exposure to soil in these 2 groups of dogs. Symptoms and signs . Symptoms and signs were
650
651
BLASTOMYCOSIS OF GENITOURINARY TRACT
related to the various organs and systems involved. The frequency of involvement of various systems and organs is listed in table 2. Skin and lungs were the most commonly affected parts of the body. The genitourinary tract was involved in 11 patients, with 21 different sites affected with blastomycosis. Table 3 shows the distribution of lesions in the genitourinary tract. Prostate and epididymis were most commonly affected. Eight patients had B. dermatitides in the prostate glands. Blastomycotic lesions were found 5 times in the left and 5 times in the right epididymis. Renal blastomycosis was found in 1 patient at autopsy. Another patient not only had epididymal involvement but also lesions " on perianal and preputial skin. This unusual location has not been reported in North American blastomycosis but is described in South American blastomycosis where it results from inoculation TABLE
2. Involvement of various sites No. Cases
Skin Lungs
34 29 21
Genitourinary
Bone and joints Miscellaneous (heart, spleen, thyroid) TABLE
18 3
3. Distribution of lesions in genitourinary organs No. Cases Prostate Epididymis: Left Right Kidney Testes Prepuce
8 5 5
1 1 1
with Paracoccidioides brasiliensis contracted during anal hygiene with leaves and bushes. 11 Although adrenal involvement has been reported elsewhere 12 we were unable to document this in any of our patients. Diagnosis. Culture of the fungus is the only absolute diagnostic proof but morphologic identification of the characteristic o·rganism from the tissues or secretions is also reliable. Skin and serologic testing are not satisfactory diagnostic procedures but may be important in epidemiologic studies. Genitourinary involvement was established in our cases by 1 of 3 methods: 1) culture from urine, abscess or prostate secretions, 2) morphologic identification of the organism in the urine or secretions or 3) histologic examination of tissue specimens. Histologic examination of the tissue specimens was the most reliable method, diagnosing 20 of 21 attempts (table 4). In blastomycosis the histopathologic pattern consists of granulomatous reactions with formation of giant cells. Microabscesses are classically present and yeast-like organisms are usually seen by either hematoxylin and eosin or Gomori stains. The fungus may be found in the giant cells or free in the abscess (see figure). Treatment. Chemotherapy is the treatment of choice but surgical excision of a localized lesion may be indicated under the umbrella of chemotherapy. There are reports of miliary spread of infection following prostatic massage. 13 The surgical procedures carried out on the genitourinary tracts of 6 patients, 3 of whom had more than 1 operation, are shown in table 5. The different modes of therapy used m our TABLE
TABLE
5. Surgical procedures
4. Diagnostic accuracy of various methods
Culture Morphologic identification Histologic examination
Total No. Tested
Positive for Blastomycosis
39 19 21
18 9 20
No. Cases Orchiectomy Epididymectomy Retropubic prostatectomy Prostatic biopsy Circumcision
Microabscess with blastomycosis dermatitides and giant cells
6 3
1 1 1
652
EICKENBERG, AMIN AND LICH TABLE
6. Therapy used in blastomycosis No. Pts.
2-hydroxystilbamidine Amphotericin B Stilbamidine Potassium iodide Irradiation Desensitization
21 18 6
24 7 1
patients are listed in table 6. Until 1950 iodides were the treatment of choice and were used in 24 of our patients. This therapy was usually a futile experience. Local irradiation and desensitization with vaccine were also used without any beneficial effect. Stilbamidine improved the prognosis but was toxic and had persisting side effects. Hydroxystilbamidine isethionate improved the prognosis; failures and relapses following iodide and stilbamidine therapy had been successfully retreated with this drug in 21 patients. In 1956 amphotericin B was introduced and given to 18 of our patients with good results. One patient, who had 2 recurrences after treatment of the genitourinary blastomycosis with potassium iodide and hydroxystilbamidine, improved dramatically on amphotericin B therapy. 14 He is free of disease 25 years after the initial diagnosis. Amphotericin B (fungizone) is a life-saving antifungal drug that is difficult to administer. 15 Because tolerance to amphotericin B varies from patient to patient, individual dosages must be adjusted to the specific requirements of each patient. It is administered intravenously after dilution with 5 per cent dextrose in water in a 0.1 mg. per cc concentration. One mg. amphotericin B diluted in 250 cc 5 per cent dextrose in water is given during a 6-hour period on the first day to assess the reaction. The dose is gradually increased to 0.25 mg. per kg. body weight and then to a maximum of 1 mg. per kg. daily. Because amphotericin B is excreted slowly the drug may be given on alternate days. A minimal total dose of 3 gm. is required. The daily dosage should be maintained at the highest level not accompanied by serious toxic manifestations. Reversible side effects of chills, fever, nausea, vomiting, hypokalemia, anemia, azotemia and decreased liver function warrant necessary precautions. A degree of renal toxicity is inevitable and necessarily accepted. The mortality rate of 90 per cent in systemic North
American blastomycosis may be reduced to as low as 10 per cent with amphotericin therapy. A relapse rate of 10 to 15 per cent may occur, sometimes years after discontinuation of therapy and, therefore, long-term followup is necessary. REFERENCES
1. Gilchrist, T. C.: Protozoan dermatitis. J. Cut. Genitourin. Dis., 12: 496, 1894.
2. Gilchrist, T. C.: A case ofblastomycotic dermatitis in man. John Hopkins Hosp. Rep., 1: 269, 1896. 3. Furcolow, M. L., Chick, E. W., Busey, J. F. and Menges, R. W.: Prevalence and incidence studies of human and canine blastomycosis. I. Cases in the United States, 1855-1968. Amer. Rev. Resp. Dis., 102: 60, 1970. 4. Denton, J. F., McDonough, E. S., Ajello, L. and Ausherman, R. J.: Isolation of Blastomyces dermatitidis from soil. Science, 133: 1126, 1961. 5. Farber, E. R., Leahy, M. S. and Meadows, T. R.: Endometrial blastomycosis acquired by sexual contact. Obst. Gynec., 32: 195, 1968. 6. Craig, M. W., Davey, W. N. and Green, R. A.: Conjugal blastomycosis. Amer. Rev. Resp. Dis., 102: 86, 1970. 7. Rolnick, D. and Baumrucker, G. 0.: Genitourinary blastomycosis: case report and review ofliterature. J. Urol., 79: 315, 1958. 8. Veterans Administration Hospitals: Blastomycosis. I. A review of 198 collected cases in Veterans Administration Hospitals. Amer. Rev. Resp. Dis., 89: 659, 1964. 9. Friedman, L. L. and Signorelli, J. J.: Blastomycosis; a brief review of literature and a report of a case involving the meninges. Ann. Intern. Med., 24: 385, 1946. 10. Turner, C., Smith, C. D. and Furcolow, M. L.: Frequency of isolation of Histoplasma capsulatum and Blastomyces dermatitidis from dogs in Kentucky. Amer. J. Vet. Res., 33: 137, 1972. 11. Londero, A. T. and Fischman, 0.: Perianal and-or rectal lesions in South American blastomycosis. Mycopathologia, 32: 231, 1967. 12. Abernathy, R. S. and Melby, J.C.: Addison's disease in North American blastomycosis. New Engl. J. Med., 266: 552, 1962. 13. Burr, A.H. and Huffines, T. R.: Blastomycosis of the prostate with miliary dissemination treated by stilbamidine. J. Urol., 71: 464, 1954. 14. Sivak, G. C. and Lich, R., Jr.: Blastomycosis treated by stilbamidine with relapse. J. Urol., 76: 678, 1956. 15. Andriole, V. T. and Kravetz, H. M.: The use of amphotericin Bin man. J.A.M.A., 180: 269, 1962.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1975 by The Williams & Wilkins Co.
BLASTOMYCOSIS OF THE GENITOURINARY TRACT HANS-UDO EICKENBERG, MOHAMMAD AMIN
AND
ROBERT LICH, JR.
From the Section of Urology, Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky
ABSTRACT
In a retrospective study of 51 cases of systemic North American blastomycosis 11 patients were found to have genitourinary tract involvement, the prostate and e idid mis bein most commonly affected. Diagnosis was made by culture of the ungus from urine, abscess or prostate secretions, morphologic identification of the characteristic organism in urine or secretions, or histologic examination of tissue specimens. Treatment with amphotericin B reduced the mortality rate of 90 per cent to as low per cent. Long-term followup is necessary because of a relapse rate of 10 to 15 per cent.
aslU
North American blastomycosis is a systemic fungal disease caused by Blastomyces dermatitides . Gilchrist first isolated this fungus in 1894 from a skin lesion.'· 2 It is sometimes known as Gilchrist's or Chicago disease. The disease has definite geographical predilections with endemic areas centering in Ohio, the Mississippi and Missouri river valleys, and along the western shores of Lake Michigan. 3 Blastomyces dermatitides is a dimorphic fungus found in the soil, which is probably the source of infection.• It is known to affect dogs and horses but there is no evidence that these animals transmit the disease. The most common mode of acquiring the infection is inhalation, producing a primary pulmonary focus . A few cases of transmission have been reported from men with prostatic involvement to their female sexual partners. 5 • 6 At room temperature it can be grown on Sabouraud's medium into a white fluffy mold-like form. In the human body or at 37C on blood agar, it grows in its yeast-like state. It spreads by hematogenous or lymphatic routes and may disseminate to any organ in the body. Genitourinary involvement accounts for 20 to 30 per cent of all the cases of systemic blastomycosis. Rolnick and Baumrucker reviewed the literature in 1958, and since then genitourinary blastomycosis is being recognized with increasing frequency. 7 MATERIAL
North American blastomycosis has been encountered in 51 cases at the University of Louisville Affiliated Hospitals in the last 25 years . Table 1 shows the patient distribution in the Veterans Administration and Louisville General Hospitals and the incidence of genitourinary tract involve ment. Genitourinary tract involvement was eviAccepted for publication August 16, 1974. Read at annual meeting of American Urological Association, St. Louis, Missouri, May 19- 23, 1974.
dent in 11 patients, which is an incidence of approximately 21.5 per cent. Diagnoses were verified either by culture or the finding of typical organisms in the tissues. Some patients studied were reported in 1964 as part of the Veterans Administration Cooperative Study on blastomycosis. • Various parameters were analyzed. Age. The patients ranged in age from 25 to 69 years. This range coincides with the reported peak incidence at 20 to 50 years. 9 The youngest patient was a 21-month-old child who had fungus cultured from blood and bone marrow but who had no evidence of genitourinary involvement. Sex. Blastomycosis is up to 15 times more common in male than in female subjects. No female patient was found to have genitourinary involvement in the cases we studied. TABLE
1. Patient distribution with blastomycosis
Hospital
Systemic
V.A.H. L.G.H . Totals
37 14 51
Genitourinary 6 5 11
Race and residence. Eight white and 3 black patients showed involvement of the genitourinary tract. All patients were either from the city of Louisville or rural Kentucky, which ranks second highest on the list of states with incidence of North American blastomycosis.• Occupation. Complete data were not available but of 5 persons with genitourinary involvement, 4 were engaged in outdoor jobs involving exposure to soil. Dogs and horses are known to carry the disease but human infection is not believed to be acquired from this source. A recent survey revealed a higher incidence of mycotic infections in dogs from rural Kentucky as compared to urban areas. 10 This incidence may be explained by different exposure to soil in these 2 groups of dogs. Symptoms and signs . Symptoms and signs were
650
651
BLASTOMYCOSIS OF GENITOURINARY TRACT
related to the various organs and systems involved. The frequency of involvement of various systems and organs is listed in table 2. Skin and lungs were the most commonly affected parts of the body. The genitourinary tract was involved in 11 patients, with 21 different sites affected with blastomycosis. Table 3 shows the distribution of lesions in the genitourinary tract. Prostate and epididymis were most commonly affected. Eight patients had B. dermatitides in the prostate glands. Blastomycotic lesions were found 5 times in the left and 5 times in the right epididymis. Renal blastomycosis was found in 1 patient at autopsy. Another patient not only had epididymal involvement but also lesions " on perianal and preputial skin. This unusual location has not been reported in North American blastomycosis but is described in South American blastomycosis where it results from inoculation TABLE
2. Involvement of various sites No. Cases
Skin Lungs
34 29 21
Genitourinary
Bone and joints Miscellaneous (heart, spleen, thyroid) TABLE
18 3
3. Distribution of lesions in genitourinary organs No. Cases Prostate Epididymis: Left Right Kidney Testes Prepuce
8 5 5
1 1 1
with Paracoccidioides brasiliensis contracted during anal hygiene with leaves and bushes. 11 Although adrenal involvement has been reported elsewhere 12 we were unable to document this in any of our patients. Diagnosis. Culture of the fungus is the only absolute diagnostic proof but morphologic identification of the characteristic o·rganism from the tissues or secretions is also reliable. Skin and serologic testing are not satisfactory diagnostic procedures but may be important in epidemiologic studies. Genitourinary involvement was established in our cases by 1 of 3 methods: 1) culture from urine, abscess or prostate secretions, 2) morphologic identification of the organism in the urine or secretions or 3) histologic examination of tissue specimens. Histologic examination of the tissue specimens was the most reliable method, diagnosing 20 of 21 attempts (table 4). In blastomycosis the histopathologic pattern consists of granulomatous reactions with formation of giant cells. Microabscesses are classically present and yeast-like organisms are usually seen by either hematoxylin and eosin or Gomori stains. The fungus may be found in the giant cells or free in the abscess (see figure). Treatment. Chemotherapy is the treatment of choice but surgical excision of a localized lesion may be indicated under the umbrella of chemotherapy. There are reports of miliary spread of infection following prostatic massage. 13 The surgical procedures carried out on the genitourinary tracts of 6 patients, 3 of whom had more than 1 operation, are shown in table 5. The different modes of therapy used m our TABLE
TABLE
5. Surgical procedures
4. Diagnostic accuracy of various methods
Culture Morphologic identification Histologic examination
Total No. Tested
Positive for Blastomycosis
39 19 21
18 9 20
No. Cases Orchiectomy Epididymectomy Retropubic prostatectomy Prostatic biopsy Circumcision
Microabscess with blastomycosis dermatitides and giant cells
6 3
1 1 1
652
EICKENBERG, AMIN AND LICH TABLE
6. Therapy used in blastomycosis No. Pts.
2-hydroxystilbamidine Amphotericin B Stilbamidine Potassium iodide Irradiation Desensitization
21 18 6
24 7 1
patients are listed in table 6. Until 1950 iodides were the treatment of choice and were used in 24 of our patients. This therapy was usually a futile experience. Local irradiation and desensitization with vaccine were also used without any beneficial effect. Stilbamidine improved the prognosis but was toxic and had persisting side effects. Hydroxystilbamidine isethionate improved the prognosis; failures and relapses following iodide and stilbamidine therapy had been successfully retreated with this drug in 21 patients. In 1956 amphotericin B was introduced and given to 18 of our patients with good results. One patient, who had 2 recurrences after treatment of the genitourinary blastomycosis with potassium iodide and hydroxystilbamidine, improved dramatically on amphotericin B therapy. 14 He is free of disease 25 years after the initial diagnosis. Amphotericin B (fungizone) is a life-saving antifungal drug that is difficult to administer. 15 Because tolerance to amphotericin B varies from patient to patient, individual dosages must be adjusted to the specific requirements of each patient. It is administered intravenously after dilution with 5 per cent dextrose in water in a 0.1 mg. per cc concentration. One mg. amphotericin B diluted in 250 cc 5 per cent dextrose in water is given during a 6-hour period on the first day to assess the reaction. The dose is gradually increased to 0.25 mg. per kg. body weight and then to a maximum of 1 mg. per kg. daily. Because amphotericin B is excreted slowly the drug may be given on alternate days. A minimal total dose of 3 gm. is required. The daily dosage should be maintained at the highest level not accompanied by serious toxic manifestations. Reversible side effects of chills, fever, nausea, vomiting, hypokalemia, anemia, azotemia and decreased liver function warrant necessary precautions. A degree of renal toxicity is inevitable and necessarily accepted. The mortality rate of 90 per cent in systemic North
American blastomycosis may be reduced to as low as 10 per cent with amphotericin therapy. A relapse rate of 10 to 15 per cent may occur, sometimes years after discontinuation of therapy and, therefore, long-term followup is necessary. REFERENCES
1. Gilchrist, T. C.: Protozoan dermatitis. J. Cut. Genitourin. Dis., 12: 496, 1894.
2. Gilchrist, T. C.: A case ofblastomycotic dermatitis in man. John Hopkins Hosp. Rep., 1: 269, 1896. 3. Furcolow, M. L., Chick, E. W., Busey, J. F. and Menges, R. W.: Prevalence and incidence studies of human and canine blastomycosis. I. Cases in the United States, 1855-1968. Amer. Rev. Resp. Dis., 102: 60, 1970. 4. Denton, J. F., McDonough, E. S., Ajello, L. and Ausherman, R. J.: Isolation of Blastomyces dermatitidis from soil. Science, 133: 1126, 1961. 5. Farber, E. R., Leahy, M. S. and Meadows, T. R.: Endometrial blastomycosis acquired by sexual contact. Obst. Gynec., 32: 195, 1968. 6. Craig, M. W., Davey, W. N. and Green, R. A.: Conjugal blastomycosis. Amer. Rev. Resp. Dis., 102: 86, 1970. 7. Rolnick, D. and Baumrucker, G. 0.: Genitourinary blastomycosis: case report and review ofliterature. J. Urol., 79: 315, 1958. 8. Veterans Administration Hospitals: Blastomycosis. I. A review of 198 collected cases in Veterans Administration Hospitals. Amer. Rev. Resp. Dis., 89: 659, 1964. 9. Friedman, L. L. and Signorelli, J. J.: Blastomycosis; a brief review of literature and a report of a case involving the meninges. Ann. Intern. Med., 24: 385, 1946. 10. Turner, C., Smith, C. D. and Furcolow, M. L.: Frequency of isolation of Histoplasma capsulatum and Blastomyces dermatitidis from dogs in Kentucky. Amer. J. Vet. Res., 33: 137, 1972. 11. Londero, A. T. and Fischman, 0.: Perianal and-or rectal lesions in South American blastomycosis. Mycopathologia, 32: 231, 1967. 12. Abernathy, R. S. and Melby, J.C.: Addison's disease in North American blastomycosis. New Engl. J. Med., 266: 552, 1962. 13. Burr, A.H. and Huffines, T. R.: Blastomycosis of the prostate with miliary dissemination treated by stilbamidine. J. Urol., 71: 464, 1954. 14. Sivak, G. C. and Lich, R., Jr.: Blastomycosis treated by stilbamidine with relapse. J. Urol., 76: 678, 1956. 15. Andriole, V. T. and Kravetz, H. M.: The use of amphotericin Bin man. J.A.M.A., 180: 269, 1962.
