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Abacterial Urethritis, Abacterial Pyuria and Reiter’s Syndrome
TnE JouRNAL OF UROLOGY
Vol. 73, No. 3, March 1955 Printed in U.S.A.
ABACTERIAL URETHRITIS, ABACTERIAL PYURIA AND REITER'S SYNDROME ANGEL F. GOLDEROS
Thirty-eight years ago, Reiter studied and described a case of urethritis, conjunctivitis and arthritis, not gonococcal in origin, which has been known since as Reiter's syndrome. As time has gone by, many reports of similar cases have appeared in the literature and our attention has been frequently called to the fact that others simulating this disease presented either urethritis and arthritis, or urethritis and conjunctivitis, accompanied by skin, preputial, mouth or eye lesions. Abacterial pyuria, as well, has likewise been brought before us evidencing certain characteristics pertaining rather to those of the so-called Reiter's syndrome. Much as been published in relation to these two entities, but careful analysis will no doubt show that urethritis has been manifest in a great percentage of them. During the past 9 years we have had the opportunity of observing three typical cases of Reiter's syndrome; three others, in which one of the components of the triad was absent; two of abacterial pyruria and still eighteen more of what we called abacterial urethritis, for their complaint at consultation was a simple urethral discharge that presented no organisms. All patients were male and only one Negro. In all, there was a history of coitus eight to twenty days before the appearance of the initial urethral manifestation, although our first examination did not always coincide with the onset of the same. Those of Reiter's syndrome, prior to the onset of the joint and eye lesions, gave a history of having suffered in the past, for two to four years, repeated episodes of urethritis which disappeared, spontaneously, within two or three weeks. This was also true of those in which one of the triad components was absent. The purely urethritic cases were of recent onset and many had never, previously, complained of any urethral manifestation, and consulted us because of a persistent discharge in spite of former treatments with penicillin, sulfas and other antibiotics, which were of no avail. In many instances the discharge, as well as the frequency, burning and occasional hematuria, had been made even worse by the use of the antibiotics. The discharges have varied in aspect, being at times grayish and mucopurulent and others, definitely purulent and yellow. Those belonging to the first type were accompanied by burning and frequency, but no particular loss of weight; the purulent ones, in contrast, had more marked manifestations of frequency, urgency, dysuria, extreme burning, nocturia, occasional hematuria and, quite often, loss of sleep and weight. Ill nourished individuals with lessened physical resistance presented more severe symptoms than the robust ones. It is relevant to emphasize the fact that these patients have been seen during the months of March to mid-November, with only a sporadic one between the middle of November to March, but even this one claimed that his initial symptomatology started within the first mentioned interval; which makes us stop Read at annual meeting, Southeastern Section of American Urological Association, Palm Beach, Fla. April 12-15, 1954.
536
ABACTERIAL URETHRITIS
537
and wonder if this manifest periodicity of occurrence may not, in some way, be related to the unproven etiology of Reiter's disease. The multiplicity of accompanying lesions observed in relation to these conditions varies from superficial erythematous manifestations of the preputial mucosa and skin to superficial ulcerations of the preputial mucosa and glans penis, violet-colored lesions of the palate, keratitis, iritis, conjunctivitis, arthritic and even extensive and generalized skin lesions, similar to psoriasis in aspect. In fact, one of our patients had undergone treatment without improvement for such an ailment and was referred to us because of the accompanying urinary symptomatology already mentioned. It was noted that each skin lesion, consisted, in its beginning, of a tiny, purulent accumulation around a hair follicle which, lasting for 24 hours, disappeared to give way to a very small, pinkish-red, and at first slightly elevated, erythematous lesion with reddish border, without scales, at times confluent, which gradually grew varied in size, forming then thick scales of grayish color. The glans penis was also covered by a thin scaly lesion which pealed off readily. Another patient was referred because of a persistent conjunctivitis and iritis limited to one eye only, its vision progressively going from bad to worse in spite of opthalmologic treatment, and whose history revealed he had suffered, on and off for two years previously, spontaneously disappearing urethritis. In the great majority we have noticed a definite, circumscribed, reddened and edematous meatal orifice lesion, and there has been present, in all, a generalized, discrete adenitis, which in itself suggests a systemic invasion, probably by way of the lymphatics, which might explain the observed multiplicity of lesions. Clinically, we consider these two manifestations most characteristic and of great help from the standpoint of diagnosis. Cystoscopy must be carried out under anesthesia, particularly if the symptomatology has persisted for some time because, otherwise, the discomfort and pain caused by the presence of the instrument, plus the distention produced by the irrigating fluid, will often force us to discontinue it. In all three diseases the cystoscopic picture is the same and, to my interpretation, of diagnostic importance. The degree of inflammation and invasion of both vesical mucosa and prostatic urethra, as well as the diminution of vesical capacity, depend on the duration or acuteness of the episode. A reddish-violet hued bladder mucosa, with little edema and mild inflammatory invasion of the neck, trigone and prostatic urethra, is noted when cystoscopy is performed immediately after the appearance of the exudate. Ten days to two weeks after the initiation of the symptoms we find, however, that not only are the inflammatory changes more intense but they may, in extension, surpass the trigone, involve the ureteral orifices and often go beyond, affecting the rest of the mucosa, in which case the bladder capacity will then be notably diminished and as a result, the mucous membrane bleeds easily if unduly distended. Catheterized specimens of urine from the kidneys will not show any bacteria. Following cystoscopy there have been no thermic reactions of any sort, in spite of the existing purulent exudates, urethral and vesical mucosal inflammatory
538
ANGEL F. GOLDER08
lesions and of the prostate, at times, which makes this a curious observation. Cases of abacterial pyuria with unilateral hydronephrosis, urethral and vesical mucosal inflammation, edema and diminution of bladder capacity, plus others with bilateral hydronephrosis and hydro-ureters, have been reported. In many, nevertheless, hydronephrosis had not been demonstrated and we have only observed it in one instance so, naturally, since this happens in some but not in all, we wonder what may be the mechanism involved in its development. The following facts stand out from the careful study of the films obtained in the hydronephrotic ones. The pelves and calyces are dilated, though the latter ones do not greatly change their normal contour; the ureter is also dilated and, often, presents marked narrowing of its inferior portion as it enters the bladder; this being, perhaps, the reason for so many reports pointing out the fact that, in such cases, catheters cannot be passed to the renal pelves. Furthermore, since wide meatotomy had to be carried out (biopsies later reported as leukoplakia) in 2 patients with abacterial urethritis~for cicatricial stenosis and thickening of the urethral meatus~because of their inability to void, we venture to point out the possibility that, in the aforementioned cases of abacterial pyuria with hydronephrosis, narrowing of the ureteral orifices may be caused by the same mechanism responsible for the meatal stenosis in those of abacterial urethritis. Thus, in those cases that develop narrowing of the ureteral orifices, intramural ureteral edema, diffused cystitis and lessened bladder capacity the patients will have, in our belief, a greater tendency to the development of hydronephrosis and hydroureter than those in whom the mucosal invasion does not go beyond the inner limits of the trigone. This interpretation may be of significance, when one considers that, occasionally, as has been reported, nephrostomy and even ureterointestinal anastomosis have been resorted to, in order to alleviate these patients. Because of the serious renal complications, disabling manifestation of arthritis, eye lesions, progressive depauperation and physical inability that some of these individuals present, I wish to stress a few simple concepts that may be of help, in diagnosis, from a practical standpoint, so that adequate and early treatment may be instituted. We must keep clearly in mind that a most detailed history should be taken, with particular reference to previous self-limiting attacks of urethritis, eye, joint, meatal or preputial manifestations, whenever a case of abacterial urethritis is suspected, for this seems to be the starting point of all three conditions. The inspection of the urethral meatus is of special interest, for its characteristic appearance cannot be confused. Look for a discrete adenitis, which later becomes generalized but is first noticed in the inguinal and femoral regions; insist, besides, on performing cystoscopy, for its typical picture is of easy interpretation and, therefore, of value. Many of these patients, as we have already mentioned, had undergone various antibiotic treatments, prior to our investigations, always without evidence of positive results. We have, instead, simply administered mapharcide, in doses of 0.06 gm. every fifth day, totaling ten to fifteen, together with polyvitamins and ample dietary regimen, with surprising and definite results, observed, often
ABACTERIAL URETHRITIS
539
enough, shortly after its institution. The decrease in the exudate, ocular, arthritic, meatal and preputial lesions, together with the notable amelioration of pain, frequency and burning on urination, have, from the start, been remarkable. Finally, the confirmed improvement of their appetite, physical aspect and wellbeing, plus the gradual disappearance of all manifestations, including the adenitis, until recuperation, should in themselves, be ample demonstration of its efficiency; considering that all the patients, as of today, apparently have remained cured. Avenida de Ital1:a 257, Havana, Cuba REFERENCES ABERHART, CARL: Abacterial pyuria, acute and chronic: Its progress and treatment. J. Urol., 63: 903, 1950. BAINES, G. H.: Abacterial pyuria and Reiter's syndrome. Brit. Med. J., 2: 605, 1947. BAUER, W. AND ENGLEMAN, E. P.: A syndrome of unknown etiology characterized by urethritis, conjunctivitis and arthritis. Trans. Assoc. Am. Phys., 47: 307, 1942. BRIGGS, W. T.: Sterile pyuria. J. Urol., 52: 283, 1944. CoLBY, F. H.: Renal complications of Reiter's disease. J. Urol., 52: 415, 1944. DUNHAM, J., RocK, J. AND BELT, E.: Isolation of a filtrable agent pathogenic for mice from case of Reiter's disease. J. Urol., 58: 212, 1947. HANKEY, S. M. AND STEPT, R.: Abacterial pyuria: response to aureomycin. J. Urol., 63: 912, 1950. HOLLANDER, J. L. ET AL.: Arthritis resembling Reiter's syndrome. J. A. M. A., 129: 593, 1945. LEVER, W. F. AND CRAWFORD, G. M.: Keratosis blenorrhagica without gonorrhea (Reiter's disease). Arch. Dermat. & Syph., 49: 389, 1944. ROSENBLUM, H. H.: So-called Reiter's disease. U.S. Nav. Med. Bull., 44: 375, 1945. SOLOMON, A. A.: Effect of arsenotherapy on upper urinary tract changes in infectious abacterial pyuria. J. Urol., 59: 252, 1948. SARGENT, J. C.: Reiter's syndrome. J. Urol., 54: 556, 1945.
Vol. 73, No. 3, March 1955 Printed in U.S.A.
ABACTERIAL URETHRITIS, ABACTERIAL PYURIA AND REITER'S SYNDROME ANGEL F. GOLDEROS
Thirty-eight years ago, Reiter studied and described a case of urethritis, conjunctivitis and arthritis, not gonococcal in origin, which has been known since as Reiter's syndrome. As time has gone by, many reports of similar cases have appeared in the literature and our attention has been frequently called to the fact that others simulating this disease presented either urethritis and arthritis, or urethritis and conjunctivitis, accompanied by skin, preputial, mouth or eye lesions. Abacterial pyuria, as well, has likewise been brought before us evidencing certain characteristics pertaining rather to those of the so-called Reiter's syndrome. Much as been published in relation to these two entities, but careful analysis will no doubt show that urethritis has been manifest in a great percentage of them. During the past 9 years we have had the opportunity of observing three typical cases of Reiter's syndrome; three others, in which one of the components of the triad was absent; two of abacterial pyruria and still eighteen more of what we called abacterial urethritis, for their complaint at consultation was a simple urethral discharge that presented no organisms. All patients were male and only one Negro. In all, there was a history of coitus eight to twenty days before the appearance of the initial urethral manifestation, although our first examination did not always coincide with the onset of the same. Those of Reiter's syndrome, prior to the onset of the joint and eye lesions, gave a history of having suffered in the past, for two to four years, repeated episodes of urethritis which disappeared, spontaneously, within two or three weeks. This was also true of those in which one of the triad components was absent. The purely urethritic cases were of recent onset and many had never, previously, complained of any urethral manifestation, and consulted us because of a persistent discharge in spite of former treatments with penicillin, sulfas and other antibiotics, which were of no avail. In many instances the discharge, as well as the frequency, burning and occasional hematuria, had been made even worse by the use of the antibiotics. The discharges have varied in aspect, being at times grayish and mucopurulent and others, definitely purulent and yellow. Those belonging to the first type were accompanied by burning and frequency, but no particular loss of weight; the purulent ones, in contrast, had more marked manifestations of frequency, urgency, dysuria, extreme burning, nocturia, occasional hematuria and, quite often, loss of sleep and weight. Ill nourished individuals with lessened physical resistance presented more severe symptoms than the robust ones. It is relevant to emphasize the fact that these patients have been seen during the months of March to mid-November, with only a sporadic one between the middle of November to March, but even this one claimed that his initial symptomatology started within the first mentioned interval; which makes us stop Read at annual meeting, Southeastern Section of American Urological Association, Palm Beach, Fla. April 12-15, 1954.
536
ABACTERIAL URETHRITIS
537
and wonder if this manifest periodicity of occurrence may not, in some way, be related to the unproven etiology of Reiter's disease. The multiplicity of accompanying lesions observed in relation to these conditions varies from superficial erythematous manifestations of the preputial mucosa and skin to superficial ulcerations of the preputial mucosa and glans penis, violet-colored lesions of the palate, keratitis, iritis, conjunctivitis, arthritic and even extensive and generalized skin lesions, similar to psoriasis in aspect. In fact, one of our patients had undergone treatment without improvement for such an ailment and was referred to us because of the accompanying urinary symptomatology already mentioned. It was noted that each skin lesion, consisted, in its beginning, of a tiny, purulent accumulation around a hair follicle which, lasting for 24 hours, disappeared to give way to a very small, pinkish-red, and at first slightly elevated, erythematous lesion with reddish border, without scales, at times confluent, which gradually grew varied in size, forming then thick scales of grayish color. The glans penis was also covered by a thin scaly lesion which pealed off readily. Another patient was referred because of a persistent conjunctivitis and iritis limited to one eye only, its vision progressively going from bad to worse in spite of opthalmologic treatment, and whose history revealed he had suffered, on and off for two years previously, spontaneously disappearing urethritis. In the great majority we have noticed a definite, circumscribed, reddened and edematous meatal orifice lesion, and there has been present, in all, a generalized, discrete adenitis, which in itself suggests a systemic invasion, probably by way of the lymphatics, which might explain the observed multiplicity of lesions. Clinically, we consider these two manifestations most characteristic and of great help from the standpoint of diagnosis. Cystoscopy must be carried out under anesthesia, particularly if the symptomatology has persisted for some time because, otherwise, the discomfort and pain caused by the presence of the instrument, plus the distention produced by the irrigating fluid, will often force us to discontinue it. In all three diseases the cystoscopic picture is the same and, to my interpretation, of diagnostic importance. The degree of inflammation and invasion of both vesical mucosa and prostatic urethra, as well as the diminution of vesical capacity, depend on the duration or acuteness of the episode. A reddish-violet hued bladder mucosa, with little edema and mild inflammatory invasion of the neck, trigone and prostatic urethra, is noted when cystoscopy is performed immediately after the appearance of the exudate. Ten days to two weeks after the initiation of the symptoms we find, however, that not only are the inflammatory changes more intense but they may, in extension, surpass the trigone, involve the ureteral orifices and often go beyond, affecting the rest of the mucosa, in which case the bladder capacity will then be notably diminished and as a result, the mucous membrane bleeds easily if unduly distended. Catheterized specimens of urine from the kidneys will not show any bacteria. Following cystoscopy there have been no thermic reactions of any sort, in spite of the existing purulent exudates, urethral and vesical mucosal inflammatory
538
ANGEL F. GOLDER08
lesions and of the prostate, at times, which makes this a curious observation. Cases of abacterial pyuria with unilateral hydronephrosis, urethral and vesical mucosal inflammation, edema and diminution of bladder capacity, plus others with bilateral hydronephrosis and hydro-ureters, have been reported. In many, nevertheless, hydronephrosis had not been demonstrated and we have only observed it in one instance so, naturally, since this happens in some but not in all, we wonder what may be the mechanism involved in its development. The following facts stand out from the careful study of the films obtained in the hydronephrotic ones. The pelves and calyces are dilated, though the latter ones do not greatly change their normal contour; the ureter is also dilated and, often, presents marked narrowing of its inferior portion as it enters the bladder; this being, perhaps, the reason for so many reports pointing out the fact that, in such cases, catheters cannot be passed to the renal pelves. Furthermore, since wide meatotomy had to be carried out (biopsies later reported as leukoplakia) in 2 patients with abacterial urethritis~for cicatricial stenosis and thickening of the urethral meatus~because of their inability to void, we venture to point out the possibility that, in the aforementioned cases of abacterial pyuria with hydronephrosis, narrowing of the ureteral orifices may be caused by the same mechanism responsible for the meatal stenosis in those of abacterial urethritis. Thus, in those cases that develop narrowing of the ureteral orifices, intramural ureteral edema, diffused cystitis and lessened bladder capacity the patients will have, in our belief, a greater tendency to the development of hydronephrosis and hydroureter than those in whom the mucosal invasion does not go beyond the inner limits of the trigone. This interpretation may be of significance, when one considers that, occasionally, as has been reported, nephrostomy and even ureterointestinal anastomosis have been resorted to, in order to alleviate these patients. Because of the serious renal complications, disabling manifestation of arthritis, eye lesions, progressive depauperation and physical inability that some of these individuals present, I wish to stress a few simple concepts that may be of help, in diagnosis, from a practical standpoint, so that adequate and early treatment may be instituted. We must keep clearly in mind that a most detailed history should be taken, with particular reference to previous self-limiting attacks of urethritis, eye, joint, meatal or preputial manifestations, whenever a case of abacterial urethritis is suspected, for this seems to be the starting point of all three conditions. The inspection of the urethral meatus is of special interest, for its characteristic appearance cannot be confused. Look for a discrete adenitis, which later becomes generalized but is first noticed in the inguinal and femoral regions; insist, besides, on performing cystoscopy, for its typical picture is of easy interpretation and, therefore, of value. Many of these patients, as we have already mentioned, had undergone various antibiotic treatments, prior to our investigations, always without evidence of positive results. We have, instead, simply administered mapharcide, in doses of 0.06 gm. every fifth day, totaling ten to fifteen, together with polyvitamins and ample dietary regimen, with surprising and definite results, observed, often
ABACTERIAL URETHRITIS
539
enough, shortly after its institution. The decrease in the exudate, ocular, arthritic, meatal and preputial lesions, together with the notable amelioration of pain, frequency and burning on urination, have, from the start, been remarkable. Finally, the confirmed improvement of their appetite, physical aspect and wellbeing, plus the gradual disappearance of all manifestations, including the adenitis, until recuperation, should in themselves, be ample demonstration of its efficiency; considering that all the patients, as of today, apparently have remained cured. Avenida de Ital1:a 257, Havana, Cuba REFERENCES ABERHART, CARL: Abacterial pyuria, acute and chronic: Its progress and treatment. J. Urol., 63: 903, 1950. BAINES, G. H.: Abacterial pyuria and Reiter's syndrome. Brit. Med. J., 2: 605, 1947. BAUER, W. AND ENGLEMAN, E. P.: A syndrome of unknown etiology characterized by urethritis, conjunctivitis and arthritis. Trans. Assoc. Am. Phys., 47: 307, 1942. BRIGGS, W. T.: Sterile pyuria. J. Urol., 52: 283, 1944. CoLBY, F. H.: Renal complications of Reiter's disease. J. Urol., 52: 415, 1944. DUNHAM, J., RocK, J. AND BELT, E.: Isolation of a filtrable agent pathogenic for mice from case of Reiter's disease. J. Urol., 58: 212, 1947. HANKEY, S. M. AND STEPT, R.: Abacterial pyuria: response to aureomycin. J. Urol., 63: 912, 1950. HOLLANDER, J. L. ET AL.: Arthritis resembling Reiter's syndrome. J. A. M. A., 129: 593, 1945. LEVER, W. F. AND CRAWFORD, G. M.: Keratosis blenorrhagica without gonorrhea (Reiter's disease). Arch. Dermat. & Syph., 49: 389, 1944. ROSENBLUM, H. H.: So-called Reiter's disease. U.S. Nav. Med. Bull., 44: 375, 1945. SOLOMON, A. A.: Effect of arsenotherapy on upper urinary tract changes in infectious abacterial pyuria. J. Urol., 59: 252, 1948. SARGENT, J. C.: Reiter's syndrome. J. Urol., 54: 556, 1945.