589
Granulomatous Prostatitis Due to Mycobacterium avium Complex Dennis J. Mikolich and Susan M. Mates
From the Division of Infectious Diseases, Department ofMedicine, Brown University; Tuberculosis Clinic, Roger Williams Medical Center; and Rhode Island Department of Health, Providence. Rhode Island
Granulomatous infections of the genitourinary tract are rare, especiallythose caused by nontuberculous mycobacteria. A case of prostatitis due to Mycobacterium avium complex in an immunocompetent man is reported. The patient had sterile pyuria, and a Mantoux skin test, using 5 tuberculin units, was positive (induration, 10 mm in diameter). Pathologic examination of the prostate revealed necrotizing granulomata with acid-fast bacilli, and repeated performance of urine cultures before initiating therapy yielded M. avium complex.
Received 25 April 1989; revised 17 June 1991. Reprints or correspondence: Dr. Dennis J. Mikolich, Department ofMedicine. Division of Infectious Diseases, Veterans Affairs Medical Center. Providence, Rhode Island 02908. Clinical Infectious Diseases 1992;14:589-91 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1402-0028$02.00
In March 1986, cystoscopy revealed gross hematuria with active bleeding from the area of the previous sigmoid colon reaction. The bladder mucosa appeared to be chronically inflamed. A suprapubic prostatectomy was performed. The prostate was enlarged, chronically inflamed, and fixed to the colon at the site of colonic surgery; the prostate could not be entirely removed. Pathologic examination of the prostate showed acute and chronic inflammation with granulomata and scattered acid-fast bacilli (figures 1 and 2). Cultures were not performed. A chest roentgenogram was normal, and the result of a Mantoux skin test was positive (induration, 10 mm in diameter). The patient denied any history of exposure to tuberculosis. In April 1986, after urine specimens were sent for culture on three separate days, therapy with isoniazid (300 mg/day) and rifampin (600 mg/day) was started. The patient received this treatment for 4 months. In July, cultures of each of the three urine specimens obtained in April yielded several colonies of an organism identified as MAC; it was reported to be resistant to isoniazid, streptomycin, ethambutol, and rifampin and sensitive to pyrazinamide. The patient had a normal complete blood cell count and serum creatinine level. Results ofliver function tests and skeletal roentgenograms were normal. Results of serologic tests for antibodies to human immunodeficiency virus were negative. Results ofan intravenous pyelogram were similar to those obtained in January 1985, except that the bladder mass was now smaller. The patient's symptoms of urinary urgency, frequency, and dysuria persisted. In August 1986, 1,000 mg of ethambutol and 1,500 mg ofpyrazinamide were added to the regimen ofison iazid and rifampin. In September, his symptoms remained unchanged. The results of urinalysis were normal (white blood cell count, 0-3/mm 3 ; red blood cell count, 0-3/mm 3) . The smears and cultures ofthree urine specimens obtained in August were negative for acid-fast bacilli. The patient's symptoms were considered to be due to a partially treated MAC infection of the remaining prostatic tissue and the bladder. A 6-week trial regimen ofansamycin (300 rug/day), isoniazid (300 mg/day), and ethambutol (1,000 mg/day) was started; 1 g of streptomycin was administered intramuscularly three times per week for the first week, then twice weekly. The Centers for Disease Control (Atlanta) con-
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Granulomatous prostatitis caused by Mycobacterium tuberculosis is well described [ 1-3]. Although cases of prostatitis due to Mycobacterium bovis and Mycobacterium kansasii have also been reported [3,4], to our knowledge, granulomatous prostatitis due to Mycobacterium avium complex (MAC) has not been described. We report a case ofgenitourinary infection with MAC that involved the prostate in an immunocompetent man. A 75-year-old man who was native to Rhode Island and who had never traveled outside the state was in good health until a transurethral prostatectomy (TURP) was performed in 1974 for benign prostatic hypertrophy. He was healthy until 1984, when he again experienced difficulty urinating, this time in association with hematuria and pyuria that worsened over the next year despite intermittent administration of trimethoprim-sulfamethoxazole (TMP-SMZ). Routine cultures were negative for pathogens. In 1985 an intravenous pyelogram showed a healthy upper urinary tract with an irregular mass at the base of the bladder that elevated the bladder floor. A second TURP was performed in March 1985. Pathologic examination of the specimen revealed nodular hyperplasia with a chronic inflammatory infiltrate. No special stainings were done. The patient received a perioperative course of TMP-SMZ. In July 1985, the patient again complained of urinary urgency and frequency and reported a new complaint ofrectal bleeding. A small polypoid carcinoma was found. Total removal of the tumor was performed in August 1985 with creation of an end-to-end anastomosis of the lower descending colon and sigmoid colon. No node involvement and no metastases were found. Postoperatively, he complained of increased urinary urgency and frequency and, for the first time, dysuria. He again had sterile pyuria and hematuria.
590
eID 1992;14 (February)
High-power view of prostate showing Langherhans' multinucleated giant cells, necrosis, and granulomata (magnification,
firmed identification of the original organism as MAC and reported sensitivity only to ansamycin and resistance to capreomycin, streptomycin, isoniazid, paraminosalicylic acid, rifampin, ethambutol, kanamycin, pyrazinamide, cycloserine, and ethionamide. The patient tolerated the new regimen well, but his symptoms did not diminish over the 6-week period. At the end of that time, therapy with all drugs was discontinued. Subsequently, the patient noted some abatement of the symptoms with the administration ofnon-steroidal antiinflammatory medications. Two years later, the patient has not experienced a relapse of the infection. MAC is the second most frequently isolated group of mycobacteria in the United States [5]; M. tuberculosis is the most frequently isolated species. Mycobacterium avium was first described as a human pathogen in 1943 [6] and may be present in both immunocompromised and immunocompetent hosts [2]. Infections due to nontuberculous mycobacteria usually occur in the respiratory tract. To our knowledge, prostate involvement has not previously been described. The presence ofMAC in the urine is not necessarily indicative ofa genitourinary tract infection. Pseudo bacteriuria with
MAC has been described [7] and was found to be caused by contamination from deionized tap water used to make phenol red solution in a laboratory. Findings of granulomatous changes of the prostate on examination of a needle biopsy specimen may represent various pathological conditions, including mycobacterial, viral, brucelloid, syphilitic, and fungal infection. Collagen vascular disease and transurethral resection have also been reported to cause prostatic granulomata [1, 8, 9]. Brooker and Aufderheide [3] have described criteria to determine the pathogenicity of mycobacteria isolated from the urine. These include symptomatology, abnormal urinary sediment, absence of other urinary pathogens, repeated growth in culture of atypical mycobacteria, and results of histopathologic examination of granulomatous tissue (ideally showing the presence of acid-fast bacilli). Mycobacteria may descend to the prostate from tuberculous kidneys; up to 85% of men with prostatic tuberculosis have renal involvement [I]. Other possible routes for infection include contiguous infection from surrounding organs and hematogenous or lymphatic spread. For our patient, the mechanism ofinfection and seeding of
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Figure 1. X400).
Mikolich and Mates
cm
1992; 14 (February)
Granulomatous Prostatitis Due to MAC
Necrotic tissue of prostate with acid-fast bacilli (magnification, Xl,OOO).
the prostate is not clear. Renal or genital involvement with MAC was not evident. Optimal treatment for prostatitis due to MAC in an immunocompetent host remains undefined but, by analogy with other diseases caused by MAC, may include both surgery and therapy with multiple antimycobacterial drugs selected on the basis of sensitivity testing results [2]. The lack of resolution of symptoms for our patient may have been due to fibrosis and scarring of the residual prostatic gland despite adequate treatment of infection [I]. A trial of antiinflammatory medication may ameliorate symptoms that do not resolve with antimycobacterial treatment. Optimal therapy for this disease is not yet defined.
Acknowledgment
The authors thank Dr. Emmanuel Wolinsky for his help in managing this case.
References I. Gorse GJ, Belshe RB. Male genital tuberculosis: a review of the literature with instructive case reports. Rev Infect Dis 1985;7:511-24. 2. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119:107-59. 3. Brooker WJ, Aufderheide AC. Genitourinary tract infections due to atypical mycobacteria. J Urol 1980;124:242-4. 4. Stoller JK. Late recurrence of mycobacterium bovis genitourinary tuberculosis: case report and review of literature. J Urol 1985; 134:565-6. 5. Good RC, Snider DE Jr. Isolation of nontuberculous mycobacteria in the United States, 1980. J Infect Dis 1982; 146:829-33. 6. Feldman WH, Davies R, Moses HE, Andberg W. An unusual mycobacterium isolated from sputum ofa man suffering from pulmonary disease of long duration. Am Rev Tuberc 1943;48:82. 7. Graham LJr, Warren NG, Tsang AY, Dalton HP. Mycobacterium avium complex pseudobacteriuria from a hospital water supply. J Clin Microbial 1988;26: 1034-6. 8. Epstein 11,Hutchins GM. Granulomatous prostatitis: distinction among allergic, nonspecific, and posttransurethral resection lesions. Hum PathoI1984;15:818-25. 9. Stillwell TJ, Engen DE, Farrow GM. The clinical spectrum ofgranulomatous prostatitis: a report of 200 cases. J Urol 1987; 138:320-3.
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Figure 2.
591
Granulomatous Prostatitis Due to Mycobacterium avium Complex Dennis J. Mikolich and Susan M. Mates
From the Division of Infectious Diseases, Department ofMedicine, Brown University; Tuberculosis Clinic, Roger Williams Medical Center; and Rhode Island Department of Health, Providence. Rhode Island
Granulomatous infections of the genitourinary tract are rare, especiallythose caused by nontuberculous mycobacteria. A case of prostatitis due to Mycobacterium avium complex in an immunocompetent man is reported. The patient had sterile pyuria, and a Mantoux skin test, using 5 tuberculin units, was positive (induration, 10 mm in diameter). Pathologic examination of the prostate revealed necrotizing granulomata with acid-fast bacilli, and repeated performance of urine cultures before initiating therapy yielded M. avium complex.
Received 25 April 1989; revised 17 June 1991. Reprints or correspondence: Dr. Dennis J. Mikolich, Department ofMedicine. Division of Infectious Diseases, Veterans Affairs Medical Center. Providence, Rhode Island 02908. Clinical Infectious Diseases 1992;14:589-91 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1402-0028$02.00
In March 1986, cystoscopy revealed gross hematuria with active bleeding from the area of the previous sigmoid colon reaction. The bladder mucosa appeared to be chronically inflamed. A suprapubic prostatectomy was performed. The prostate was enlarged, chronically inflamed, and fixed to the colon at the site of colonic surgery; the prostate could not be entirely removed. Pathologic examination of the prostate showed acute and chronic inflammation with granulomata and scattered acid-fast bacilli (figures 1 and 2). Cultures were not performed. A chest roentgenogram was normal, and the result of a Mantoux skin test was positive (induration, 10 mm in diameter). The patient denied any history of exposure to tuberculosis. In April 1986, after urine specimens were sent for culture on three separate days, therapy with isoniazid (300 mg/day) and rifampin (600 mg/day) was started. The patient received this treatment for 4 months. In July, cultures of each of the three urine specimens obtained in April yielded several colonies of an organism identified as MAC; it was reported to be resistant to isoniazid, streptomycin, ethambutol, and rifampin and sensitive to pyrazinamide. The patient had a normal complete blood cell count and serum creatinine level. Results ofliver function tests and skeletal roentgenograms were normal. Results of serologic tests for antibodies to human immunodeficiency virus were negative. Results ofan intravenous pyelogram were similar to those obtained in January 1985, except that the bladder mass was now smaller. The patient's symptoms of urinary urgency, frequency, and dysuria persisted. In August 1986, 1,000 mg of ethambutol and 1,500 mg ofpyrazinamide were added to the regimen ofison iazid and rifampin. In September, his symptoms remained unchanged. The results of urinalysis were normal (white blood cell count, 0-3/mm 3 ; red blood cell count, 0-3/mm 3) . The smears and cultures ofthree urine specimens obtained in August were negative for acid-fast bacilli. The patient's symptoms were considered to be due to a partially treated MAC infection of the remaining prostatic tissue and the bladder. A 6-week trial regimen ofansamycin (300 rug/day), isoniazid (300 mg/day), and ethambutol (1,000 mg/day) was started; 1 g of streptomycin was administered intramuscularly three times per week for the first week, then twice weekly. The Centers for Disease Control (Atlanta) con-
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Granulomatous prostatitis caused by Mycobacterium tuberculosis is well described [ 1-3]. Although cases of prostatitis due to Mycobacterium bovis and Mycobacterium kansasii have also been reported [3,4], to our knowledge, granulomatous prostatitis due to Mycobacterium avium complex (MAC) has not been described. We report a case ofgenitourinary infection with MAC that involved the prostate in an immunocompetent man. A 75-year-old man who was native to Rhode Island and who had never traveled outside the state was in good health until a transurethral prostatectomy (TURP) was performed in 1974 for benign prostatic hypertrophy. He was healthy until 1984, when he again experienced difficulty urinating, this time in association with hematuria and pyuria that worsened over the next year despite intermittent administration of trimethoprim-sulfamethoxazole (TMP-SMZ). Routine cultures were negative for pathogens. In 1985 an intravenous pyelogram showed a healthy upper urinary tract with an irregular mass at the base of the bladder that elevated the bladder floor. A second TURP was performed in March 1985. Pathologic examination of the specimen revealed nodular hyperplasia with a chronic inflammatory infiltrate. No special stainings were done. The patient received a perioperative course of TMP-SMZ. In July 1985, the patient again complained of urinary urgency and frequency and reported a new complaint ofrectal bleeding. A small polypoid carcinoma was found. Total removal of the tumor was performed in August 1985 with creation of an end-to-end anastomosis of the lower descending colon and sigmoid colon. No node involvement and no metastases were found. Postoperatively, he complained of increased urinary urgency and frequency and, for the first time, dysuria. He again had sterile pyuria and hematuria.
590
eID 1992;14 (February)
High-power view of prostate showing Langherhans' multinucleated giant cells, necrosis, and granulomata (magnification,
firmed identification of the original organism as MAC and reported sensitivity only to ansamycin and resistance to capreomycin, streptomycin, isoniazid, paraminosalicylic acid, rifampin, ethambutol, kanamycin, pyrazinamide, cycloserine, and ethionamide. The patient tolerated the new regimen well, but his symptoms did not diminish over the 6-week period. At the end of that time, therapy with all drugs was discontinued. Subsequently, the patient noted some abatement of the symptoms with the administration ofnon-steroidal antiinflammatory medications. Two years later, the patient has not experienced a relapse of the infection. MAC is the second most frequently isolated group of mycobacteria in the United States [5]; M. tuberculosis is the most frequently isolated species. Mycobacterium avium was first described as a human pathogen in 1943 [6] and may be present in both immunocompromised and immunocompetent hosts [2]. Infections due to nontuberculous mycobacteria usually occur in the respiratory tract. To our knowledge, prostate involvement has not previously been described. The presence ofMAC in the urine is not necessarily indicative ofa genitourinary tract infection. Pseudo bacteriuria with
MAC has been described [7] and was found to be caused by contamination from deionized tap water used to make phenol red solution in a laboratory. Findings of granulomatous changes of the prostate on examination of a needle biopsy specimen may represent various pathological conditions, including mycobacterial, viral, brucelloid, syphilitic, and fungal infection. Collagen vascular disease and transurethral resection have also been reported to cause prostatic granulomata [1, 8, 9]. Brooker and Aufderheide [3] have described criteria to determine the pathogenicity of mycobacteria isolated from the urine. These include symptomatology, abnormal urinary sediment, absence of other urinary pathogens, repeated growth in culture of atypical mycobacteria, and results of histopathologic examination of granulomatous tissue (ideally showing the presence of acid-fast bacilli). Mycobacteria may descend to the prostate from tuberculous kidneys; up to 85% of men with prostatic tuberculosis have renal involvement [I]. Other possible routes for infection include contiguous infection from surrounding organs and hematogenous or lymphatic spread. For our patient, the mechanism ofinfection and seeding of
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Figure 1. X400).
Mikolich and Mates
cm
1992; 14 (February)
Granulomatous Prostatitis Due to MAC
Necrotic tissue of prostate with acid-fast bacilli (magnification, Xl,OOO).
the prostate is not clear. Renal or genital involvement with MAC was not evident. Optimal treatment for prostatitis due to MAC in an immunocompetent host remains undefined but, by analogy with other diseases caused by MAC, may include both surgery and therapy with multiple antimycobacterial drugs selected on the basis of sensitivity testing results [2]. The lack of resolution of symptoms for our patient may have been due to fibrosis and scarring of the residual prostatic gland despite adequate treatment of infection [I]. A trial of antiinflammatory medication may ameliorate symptoms that do not resolve with antimycobacterial treatment. Optimal therapy for this disease is not yet defined.
Acknowledgment
The authors thank Dr. Emmanuel Wolinsky for his help in managing this case.
References I. Gorse GJ, Belshe RB. Male genital tuberculosis: a review of the literature with instructive case reports. Rev Infect Dis 1985;7:511-24. 2. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119:107-59. 3. Brooker WJ, Aufderheide AC. Genitourinary tract infections due to atypical mycobacteria. J Urol 1980;124:242-4. 4. Stoller JK. Late recurrence of mycobacterium bovis genitourinary tuberculosis: case report and review of literature. J Urol 1985; 134:565-6. 5. Good RC, Snider DE Jr. Isolation of nontuberculous mycobacteria in the United States, 1980. J Infect Dis 1982; 146:829-33. 6. Feldman WH, Davies R, Moses HE, Andberg W. An unusual mycobacterium isolated from sputum ofa man suffering from pulmonary disease of long duration. Am Rev Tuberc 1943;48:82. 7. Graham LJr, Warren NG, Tsang AY, Dalton HP. Mycobacterium avium complex pseudobacteriuria from a hospital water supply. J Clin Microbial 1988;26: 1034-6. 8. Epstein 11,Hutchins GM. Granulomatous prostatitis: distinction among allergic, nonspecific, and posttransurethral resection lesions. Hum PathoI1984;15:818-25. 9. Stillwell TJ, Engen DE, Farrow GM. The clinical spectrum ofgranulomatous prostatitis: a report of 200 cases. J Urol 1987; 138:320-3.
Downloaded from http://cid.oxfordjournals.org/ at University of Arizona on July 6, 2015
Figure 2.
591
