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Genitourinary Tract Infections Due to Atypical Mycobacteria
0022-5347 /80/1241-0242$02.00/0 Vol. 124, August Printed in U.S. A.
THE JOURNAL OF UROLOGY
Copyright© 1980 by The Williams & Wilkins Co.
GENITOURINARY TRACT INFECTIONS DUE TO ATYPICAL MY CO BACTERIA WARREN J. BROOKER*
AND
ARTHUR C. AUFDERHEIDE
From the Department of Urology, St. Luke's Hospital and Department of Pathology, University of Minnesota, Duluth School of Medicine, Duluth, Minnesota
ABSTRACT
A patient with chronic prostatitis caused by Mycobacterium kansasii is reported, demonstrating that these organisms occasionally cause urinary tract infections. Criteria useful in evaluating the clinical significance of atypical mycobacteria isolated from the urine are suggested. Application of these criteria to 19 patients encountered in routine clinical practice demonstrates their usefulness. The diagnostic pursuit of chronic or recurrent urinary tract infection occasionally results in the isolation of an atypical mycobacterium in the urine. Many physicians dismiss such a finding as having no etiologic significance. We herein reaffirm the infectious potential of these organisms in the urinary tract by reporting on a patient with chronic prostatitis due to an atypical mycobacterium (M. kansasii) and suggest criteria useful in evaluating the clinical significance of the presence of these organisms in the urine. MATERIAL AND METHODS
The records of all patients with urine cultures positive for atypical mycobacteria at our hospital from January 1977 to August 1978 were reviewed (table 1). Standard laboratory methodology for isolation and identification of typical and atypical mycobacteria was used. 1 Confirmation of identification was done by the laboratories of the Minnesota Department of Health. Criteria were developed to determine the etiologic role of these organisms and were used to evaluate whether the mycobacterial organism isolated from the urine of these patients actually was producing a urinary tract infection. Criteria that we believed enhanced the probability that such an organism was causing disease in the patient included 1) symptoms of chronic or recurrent urinary infection, 2) endoscopic and/or radiologic evidence of genitourinary infection, 3) abnormal urine sediment, 4) absence of other urinary pathogens, 5) repeated culturally demonstrable atypical mycobacteria and 6) granulomatous tissue histology, preferably demonstrated to contain acid-fast bacilli. Finally, the records of all hospitals in the area were searched for patients with urinary tract infections due to atypical mycobacteria. RESULTS
The results of retrospective application of the aforementioned criteria to the 19 patients we encountered in clinical practice in 1977 and 1978 were recorded (table 1). None of the patients met all 6 criteria. Nine patients were discharged from the hospital without a definitive diagnosis. Review of hospital records revealed 1 patient who met all the criteria suggested. CASE REPORT
In 1958 a 59-year-old Wisconsin farmer suffered gross hematuria with acute urinary retention. Office visits during the previous 2 years had identified urinary hesitancy, dysuria, persistent micropyuria, microhematuria and a nodular prostate. Accepted for publication October 19, 1979. * Requests for reprints: St. Luke's Hospital, 915 East First St., Duluth, Minnesota 55805.
Multiple granulomas without demonstrable acid-fast bacilli were noted in the 5 gm. prostatic tissue resected transurethrally. A tuberculin test was positive but postoperative urine cultures were negative for gram-negative and acid-fast bacilli. Treatment with 200 mg. isonicotinic acid hydrazide 3 times daily was given for 1 year. In 1964 micropyuria was noted during hospitalization for a gastric ulcer. Routine urine cultures showed no growth but acid-fast cultures on 4 daily specimens all yielded M. kansasii. This organism showed partial resistance to 2.5 mg./ ml. isonicotinic acid hydrazide and to 3.5 mg./ml. streptomycin but none to paraminosalicylic acid. No further antibiotic therapy was offered. In 1967 hematuria again led to transurethral prostatic resection and, again, granulomas were noted and M. kansasii was found in the urine. In 1971 excretory urography revealed an atrophic right kidney. In 1973 subtotal gastrectomy for a gastric ulcer was followed by a fatal pulmonary embolus. The partial autopsy revealed no pulmonary granulomas nor any in the atrophic kidney, which was infiltrated diffusely with lymphocytes. Unfortunately, the bladder, prostate and scrotal contents were not examined. DISCUSSION
Atypical mycobacteria occasionally infect the human urif!ary tract. The organisms also may be found in the urine of patients without urinary disease. The clinical problem resolves itself into establishing criteria by which to judge relevance of the presence of atypical mycobacteria in urine. Mycobacteria other than M. tuberculosis, M. leprae and M. bovis are commonly termed atypical and still are classified into 4 major groups according to certain laboratory characteristics (table 2). 2 More detailed biochemical study has permitted the identification of a number of species within these groups. While the human infections caused by these organisms generally resemble those of M. tuberculosis clinically and pathologically they differ in their greater variation in virulence (usually much lower), tuberculin skin test response and sensitivity to the usual antituberculous medications. An important difference is that man-to-man transmission has not been documented. Their presence in air, dust or water may result in their incidental appearance in human tissues or fluids, complicating the interpretation of their presence. Since M. tuberculosis is a urinary pathogen it is curious that there are so few reports of atypical mycobacteria causing urinary disease. These few reports together with the patient described herein are summarized in table 3. 3- 9 The clinical value of our criteria becomes apparent when they are applied in retrospect to our 19 patients. The first 4 criteria serve to alert the physician, leading him to procure further specimens for study. The fifth criterion increases substantially the probability of the organism's etiologic signifi-
242
243
ATYPICAL MYCOBACTERIAL GENITOURINARY INFECTIONS TABLE
Age-Sex (yrs.)
1. Application of significance criteria to 19 patients Mycobacterium Type in Urine
Criteria*
Comments Cultures Pos./Total
No. 14-M 68-M
Hemorrhagic cystitis, cause? Benign prostatic hypertrophy, needle biopsy Metastatic Ca to kidney, pelvic urine Cystitis, prostatic Ca
80-M 85-M 40-M 20-F 4-F 48-F 74-M 30-M 74-M 78-F 52-F 36-F 71-M 77-F 49-F 14-M 26-M
II II
2/2 1/2
II, III III III III III III III
Microhematuria, cause?
Renal calculus and pyelonephritis "Sterile" pyuria, cause? Renal calculus and pyelonephritis "Sterile" pyuria, cause?
Ileitis, bladder fistula Prostate Ca Cystitis, Escherichia coli sepsis Urethritis Postpartum hematuria, cause? Retention after colectomy "Sterile" pyuria, cause? Rt. upper quadrant pain, cause?
1/1 1/1 1/3 1/3 2/3 1/4 1/1 1/9 1/3 1/3 1/1 1/4 1/3 1/2 1/3 1/5 1/3
III
III IV IV IV IV IV IV IV IV
Hematuria, cause?
Obstructive pyelonephritis
2
3
4
5
6
+t +
+ +
+ +
+ +
+
0
+
+ ?
0 0
+ + + + + + + + +
+
+ + + + + + +
+ + + + + +
+ + +
+
+ + + + + + + + + + + + + +
+
0 0 0 0
0
0
+ + + + + + +
0
0 0 0 0 0 0 0
* I-symptoms of chronic or recurrent urinary infection, 2-endoscopic and/or radiologic evidence of genitourinary infection, 3-abnormal urine sediment, 4absence of other urinary pathogens, 5-repeated culturally demonstrable atypical mycobacteria and 6-granulomatous tissue histology, preferably demonstrated to contain acid-fast bacilli. t +, positive. -, negative. 0, not studied. TABLE
2. Characteristics of atypical mycobacteria groups Group
II Pigment production Typical species Usual sites of human infection In vitro growth time
III
IV None in either light or dark
Cervical lymph nodes
Non-photochromogen (none in either light or dark) Battey-Avium-Swine complex; M. gastri, M. terrae Lung
M. fortuitum, M. phlei, M. smegmatis Rare, lung (aspiration)
Weeks
Weeks
2-10 days (rapid growers)
Photochromogen (only upon light exposure) M. kansasii
Scotochromogen in dark) M. scrofulaceum
Lung, skin Weeks
TABLE
(formed
3. Summary of reported atypical mycobacterial genitourinary injections Urine Culture For Atypical Mycobacteria
Tissue Culture For Atypical Mycobacteria
Prostate, rt. and It. epididyrnides
Not studied
Not studied
McCusker and Green'
Kidney
Not studied
Lester' Hepper and associates6
Kidney 1-epididymis, Case case 2-both epididyrnides Kidney
Not studied Case I-neg. (postop.), case 2-M. kansasii
Abdominal nodes, lung, blood, ascites pos. Not studied Both cases-M. kansasii
M. kansasii
Kidney-M. kansasii
Faber and associates
Kidney
Battey
Kidney-neg.
Newman'
Kidney
Kidney-neg.
Present study
Prostate
Battey, also intravenous M. kansasii
Reference
Affected Organs
Wood and associates3
Listwan
and
associ-
ates7 8
Not studied
cance, while the sixth is considered confirmatory, particularly if the organism can be cultured from the tissue specimen. The atypical bacterium isolated cannot be incriminated as causing disease in any of these 19 patients with the information available. The studies necessary to make appropriate judgment (multiple cultures, biopsies and so forth) were not done. Had they been done it is possible that they may have led to a definitive diagnosis in ~1 of these patients. When atypical mycobacteria are identified in urine or tissues application of these criteria reminds the physician to procure studies necessary for diagnosis. Other factors influencing the physician's judgment should include the organism's classification. Groups I and III organisms
Histology
Comments
Prostatic granulomas, caseous granulomas in epididymides, acid-fast bacillus stains not reported Renal granulomas, acidfast bacillus stains pos.
"Yellow bacillus" in sputum, no reference to urine or tissue culture
Not studied Both cases caseous granuloma, acid-fast bacillus stain pos. Renal granulomas, acidfast bacillus stain neg. Non-specific inflammation, acid-fast bacillus stain neg. Renal granulomas, acidfast bacillus stain pos. Granulomas, acid-fast bacillus stain neg.
Myeloid leukemia with disseminated infection No details, 2 pts.
Pancytopenia with disseminated infection
have been associated with genitourinary infections to date. Group IV organisms rarely cause disease and so probably deserve less concern. The sudden appearance of a cluster of positive culture reports in different patients may reflect contamination of a laboratory's culture processing system. These observations led us to the following suggestions: 1) cultural isolation of atypical mycobacteria, especially group I or III, from the urine of a patient with findings of genitourinary infection should lead one to suspect their pathogenicity and to perform further studies and 2) further studies should include repeated urine cultures and tissue biopsy of the suspected involved area. The tissue should be cultured and its histologic examination should include acid-fast stains.
BROOKER AND AUFDERHEIDE
244
Dr. Harold Walder allowed us to include the patient reported herein. REFERENCES 1. Finegold, S. M., Martin, W. J. and Scott, E.G.: Bailey and Scott's Diagnostic Microbiology, 5th ed. St. Louis: The C. V. Mosby Co., pp. 239-263, 1978. 2. Runyon, E. H.: Anonymous rnycobacteria in pulmonary disease. Med. Clin. N. Arner., 43: 273, 1959. 3. Wood, L. E., Buhler, V. B. and Pollak, A.: Human infection with the "yellow" acid-fast bacillus; report of 15 additional cases. Arner. Rev. Tuberc., 73: 917, 1956. 4. McCusker, J. J. and Green, R. A.: Generalized nontuberculous rnycobacteriosis. Report of two cases. Arner. Rev. Resp. Dis., 86: 405, 1962. 5. Lester, W.: Unclassified rnycobacterial diseases. Ann. Rev. Med., 17: 351, 1966. 6. Hepper, N. G. G., Karlson, G. A., Leary, J. F. and Soule, E. H.:
Genitourinary infection due to Mycobacteriurn kansasii. Mayo Clin. Proc., 46: 387, 1971. 7. Listwan, W. J., Roth, D. A., Tsung, S. H. and Rose, H. D.: Disseminated Mycobacteriurn kansasii infection with pancytopenia and interstitial nephritis. Ann. Intern. Med., 83: 70, 1975. 8. Faber, D. R., Lasky, I. I. and Goodwin, W. E.: Idiopathic unilateral renal hernaturia associated with atypical acid-fast bacillus: Battey type. Cure by partial nephrectorny. J. Urol., 93: 435, 1965. 9. Newman, H.: Renal disease associated with atypical rnycobacteria: Battey type. Case report. J. Urol., 103: 403, 1970.
EDITORIAL COMMENT
It is well known that the presence of acid-fast bacteria in the urine is not diagnostic of tissue infection. The authors have proposed reasonable standards for establishing the diagnosis. They illustrate this nicely in the case presentation. C.M.K.
THE JOURNAL OF UROLOGY
Copyright© 1980 by The Williams & Wilkins Co.
GENITOURINARY TRACT INFECTIONS DUE TO ATYPICAL MY CO BACTERIA WARREN J. BROOKER*
AND
ARTHUR C. AUFDERHEIDE
From the Department of Urology, St. Luke's Hospital and Department of Pathology, University of Minnesota, Duluth School of Medicine, Duluth, Minnesota
ABSTRACT
A patient with chronic prostatitis caused by Mycobacterium kansasii is reported, demonstrating that these organisms occasionally cause urinary tract infections. Criteria useful in evaluating the clinical significance of atypical mycobacteria isolated from the urine are suggested. Application of these criteria to 19 patients encountered in routine clinical practice demonstrates their usefulness. The diagnostic pursuit of chronic or recurrent urinary tract infection occasionally results in the isolation of an atypical mycobacterium in the urine. Many physicians dismiss such a finding as having no etiologic significance. We herein reaffirm the infectious potential of these organisms in the urinary tract by reporting on a patient with chronic prostatitis due to an atypical mycobacterium (M. kansasii) and suggest criteria useful in evaluating the clinical significance of the presence of these organisms in the urine. MATERIAL AND METHODS
The records of all patients with urine cultures positive for atypical mycobacteria at our hospital from January 1977 to August 1978 were reviewed (table 1). Standard laboratory methodology for isolation and identification of typical and atypical mycobacteria was used. 1 Confirmation of identification was done by the laboratories of the Minnesota Department of Health. Criteria were developed to determine the etiologic role of these organisms and were used to evaluate whether the mycobacterial organism isolated from the urine of these patients actually was producing a urinary tract infection. Criteria that we believed enhanced the probability that such an organism was causing disease in the patient included 1) symptoms of chronic or recurrent urinary infection, 2) endoscopic and/or radiologic evidence of genitourinary infection, 3) abnormal urine sediment, 4) absence of other urinary pathogens, 5) repeated culturally demonstrable atypical mycobacteria and 6) granulomatous tissue histology, preferably demonstrated to contain acid-fast bacilli. Finally, the records of all hospitals in the area were searched for patients with urinary tract infections due to atypical mycobacteria. RESULTS
The results of retrospective application of the aforementioned criteria to the 19 patients we encountered in clinical practice in 1977 and 1978 were recorded (table 1). None of the patients met all 6 criteria. Nine patients were discharged from the hospital without a definitive diagnosis. Review of hospital records revealed 1 patient who met all the criteria suggested. CASE REPORT
In 1958 a 59-year-old Wisconsin farmer suffered gross hematuria with acute urinary retention. Office visits during the previous 2 years had identified urinary hesitancy, dysuria, persistent micropyuria, microhematuria and a nodular prostate. Accepted for publication October 19, 1979. * Requests for reprints: St. Luke's Hospital, 915 East First St., Duluth, Minnesota 55805.
Multiple granulomas without demonstrable acid-fast bacilli were noted in the 5 gm. prostatic tissue resected transurethrally. A tuberculin test was positive but postoperative urine cultures were negative for gram-negative and acid-fast bacilli. Treatment with 200 mg. isonicotinic acid hydrazide 3 times daily was given for 1 year. In 1964 micropyuria was noted during hospitalization for a gastric ulcer. Routine urine cultures showed no growth but acid-fast cultures on 4 daily specimens all yielded M. kansasii. This organism showed partial resistance to 2.5 mg./ ml. isonicotinic acid hydrazide and to 3.5 mg./ml. streptomycin but none to paraminosalicylic acid. No further antibiotic therapy was offered. In 1967 hematuria again led to transurethral prostatic resection and, again, granulomas were noted and M. kansasii was found in the urine. In 1971 excretory urography revealed an atrophic right kidney. In 1973 subtotal gastrectomy for a gastric ulcer was followed by a fatal pulmonary embolus. The partial autopsy revealed no pulmonary granulomas nor any in the atrophic kidney, which was infiltrated diffusely with lymphocytes. Unfortunately, the bladder, prostate and scrotal contents were not examined. DISCUSSION
Atypical mycobacteria occasionally infect the human urif!ary tract. The organisms also may be found in the urine of patients without urinary disease. The clinical problem resolves itself into establishing criteria by which to judge relevance of the presence of atypical mycobacteria in urine. Mycobacteria other than M. tuberculosis, M. leprae and M. bovis are commonly termed atypical and still are classified into 4 major groups according to certain laboratory characteristics (table 2). 2 More detailed biochemical study has permitted the identification of a number of species within these groups. While the human infections caused by these organisms generally resemble those of M. tuberculosis clinically and pathologically they differ in their greater variation in virulence (usually much lower), tuberculin skin test response and sensitivity to the usual antituberculous medications. An important difference is that man-to-man transmission has not been documented. Their presence in air, dust or water may result in their incidental appearance in human tissues or fluids, complicating the interpretation of their presence. Since M. tuberculosis is a urinary pathogen it is curious that there are so few reports of atypical mycobacteria causing urinary disease. These few reports together with the patient described herein are summarized in table 3. 3- 9 The clinical value of our criteria becomes apparent when they are applied in retrospect to our 19 patients. The first 4 criteria serve to alert the physician, leading him to procure further specimens for study. The fifth criterion increases substantially the probability of the organism's etiologic signifi-
242
243
ATYPICAL MYCOBACTERIAL GENITOURINARY INFECTIONS TABLE
Age-Sex (yrs.)
1. Application of significance criteria to 19 patients Mycobacterium Type in Urine
Criteria*
Comments Cultures Pos./Total
No. 14-M 68-M
Hemorrhagic cystitis, cause? Benign prostatic hypertrophy, needle biopsy Metastatic Ca to kidney, pelvic urine Cystitis, prostatic Ca
80-M 85-M 40-M 20-F 4-F 48-F 74-M 30-M 74-M 78-F 52-F 36-F 71-M 77-F 49-F 14-M 26-M
II II
2/2 1/2
II, III III III III III III III
Microhematuria, cause?
Renal calculus and pyelonephritis "Sterile" pyuria, cause? Renal calculus and pyelonephritis "Sterile" pyuria, cause?
Ileitis, bladder fistula Prostate Ca Cystitis, Escherichia coli sepsis Urethritis Postpartum hematuria, cause? Retention after colectomy "Sterile" pyuria, cause? Rt. upper quadrant pain, cause?
1/1 1/1 1/3 1/3 2/3 1/4 1/1 1/9 1/3 1/3 1/1 1/4 1/3 1/2 1/3 1/5 1/3
III
III IV IV IV IV IV IV IV IV
Hematuria, cause?
Obstructive pyelonephritis
2
3
4
5
6
+t +
+ +
+ +
+ +
+
0
+
+ ?
0 0
+ + + + + + + + +
+
+ + + + + + +
+ + + + + +
+ + +
+
+ + + + + + + + + + + + + +
+
0 0 0 0
0
0
+ + + + + + +
0
0 0 0 0 0 0 0
* I-symptoms of chronic or recurrent urinary infection, 2-endoscopic and/or radiologic evidence of genitourinary infection, 3-abnormal urine sediment, 4absence of other urinary pathogens, 5-repeated culturally demonstrable atypical mycobacteria and 6-granulomatous tissue histology, preferably demonstrated to contain acid-fast bacilli. t +, positive. -, negative. 0, not studied. TABLE
2. Characteristics of atypical mycobacteria groups Group
II Pigment production Typical species Usual sites of human infection In vitro growth time
III
IV None in either light or dark
Cervical lymph nodes
Non-photochromogen (none in either light or dark) Battey-Avium-Swine complex; M. gastri, M. terrae Lung
M. fortuitum, M. phlei, M. smegmatis Rare, lung (aspiration)
Weeks
Weeks
2-10 days (rapid growers)
Photochromogen (only upon light exposure) M. kansasii
Scotochromogen in dark) M. scrofulaceum
Lung, skin Weeks
TABLE
(formed
3. Summary of reported atypical mycobacterial genitourinary injections Urine Culture For Atypical Mycobacteria
Tissue Culture For Atypical Mycobacteria
Prostate, rt. and It. epididyrnides
Not studied
Not studied
McCusker and Green'
Kidney
Not studied
Lester' Hepper and associates6
Kidney 1-epididymis, Case case 2-both epididyrnides Kidney
Not studied Case I-neg. (postop.), case 2-M. kansasii
Abdominal nodes, lung, blood, ascites pos. Not studied Both cases-M. kansasii
M. kansasii
Kidney-M. kansasii
Faber and associates
Kidney
Battey
Kidney-neg.
Newman'
Kidney
Kidney-neg.
Present study
Prostate
Battey, also intravenous M. kansasii
Reference
Affected Organs
Wood and associates3
Listwan
and
associ-
ates7 8
Not studied
cance, while the sixth is considered confirmatory, particularly if the organism can be cultured from the tissue specimen. The atypical bacterium isolated cannot be incriminated as causing disease in any of these 19 patients with the information available. The studies necessary to make appropriate judgment (multiple cultures, biopsies and so forth) were not done. Had they been done it is possible that they may have led to a definitive diagnosis in ~1 of these patients. When atypical mycobacteria are identified in urine or tissues application of these criteria reminds the physician to procure studies necessary for diagnosis. Other factors influencing the physician's judgment should include the organism's classification. Groups I and III organisms
Histology
Comments
Prostatic granulomas, caseous granulomas in epididymides, acid-fast bacillus stains not reported Renal granulomas, acidfast bacillus stains pos.
"Yellow bacillus" in sputum, no reference to urine or tissue culture
Not studied Both cases caseous granuloma, acid-fast bacillus stain pos. Renal granulomas, acidfast bacillus stain neg. Non-specific inflammation, acid-fast bacillus stain neg. Renal granulomas, acidfast bacillus stain pos. Granulomas, acid-fast bacillus stain neg.
Myeloid leukemia with disseminated infection No details, 2 pts.
Pancytopenia with disseminated infection
have been associated with genitourinary infections to date. Group IV organisms rarely cause disease and so probably deserve less concern. The sudden appearance of a cluster of positive culture reports in different patients may reflect contamination of a laboratory's culture processing system. These observations led us to the following suggestions: 1) cultural isolation of atypical mycobacteria, especially group I or III, from the urine of a patient with findings of genitourinary infection should lead one to suspect their pathogenicity and to perform further studies and 2) further studies should include repeated urine cultures and tissue biopsy of the suspected involved area. The tissue should be cultured and its histologic examination should include acid-fast stains.
BROOKER AND AUFDERHEIDE
244
Dr. Harold Walder allowed us to include the patient reported herein. REFERENCES 1. Finegold, S. M., Martin, W. J. and Scott, E.G.: Bailey and Scott's Diagnostic Microbiology, 5th ed. St. Louis: The C. V. Mosby Co., pp. 239-263, 1978. 2. Runyon, E. H.: Anonymous rnycobacteria in pulmonary disease. Med. Clin. N. Arner., 43: 273, 1959. 3. Wood, L. E., Buhler, V. B. and Pollak, A.: Human infection with the "yellow" acid-fast bacillus; report of 15 additional cases. Arner. Rev. Tuberc., 73: 917, 1956. 4. McCusker, J. J. and Green, R. A.: Generalized nontuberculous rnycobacteriosis. Report of two cases. Arner. Rev. Resp. Dis., 86: 405, 1962. 5. Lester, W.: Unclassified rnycobacterial diseases. Ann. Rev. Med., 17: 351, 1966. 6. Hepper, N. G. G., Karlson, G. A., Leary, J. F. and Soule, E. H.:
Genitourinary infection due to Mycobacteriurn kansasii. Mayo Clin. Proc., 46: 387, 1971. 7. Listwan, W. J., Roth, D. A., Tsung, S. H. and Rose, H. D.: Disseminated Mycobacteriurn kansasii infection with pancytopenia and interstitial nephritis. Ann. Intern. Med., 83: 70, 1975. 8. Faber, D. R., Lasky, I. I. and Goodwin, W. E.: Idiopathic unilateral renal hernaturia associated with atypical acid-fast bacillus: Battey type. Cure by partial nephrectorny. J. Urol., 93: 435, 1965. 9. Newman, H.: Renal disease associated with atypical rnycobacteria: Battey type. Case report. J. Urol., 103: 403, 1970.
EDITORIAL COMMENT
It is well known that the presence of acid-fast bacteria in the urine is not diagnostic of tissue infection. The authors have proposed reasonable standards for establishing the diagnosis. They illustrate this nicely in the case presentation. C.M.K.