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Necrotizing cystitis
NECROTIZING CYSTITIS Secondary to "Bootleg" Methaqualone M O R T O N G O L D F A R B , M.D. R O B E R T F I N E L L I , M.D. From the Department of Urology, Nassau County Medieal Center, East Meadow, N e w York
A B S T R A C T - G r o s s painful hematuria in 8 young adults who consumed "'bootleg" methaqualone (Quaalude) is reported. The cause o f this condition is ortho-toluidine, a compound involved in the synthesis o f methaqualone. A case report and structure o f the lesion is presented.
Methaqualone (Quaalude), "pharmacologically equivalent" to the short and intermediate-acting barbiturates, has entered the arena of desired, and commonly available, drugs of abuse. 1 Urinary tract bleeding has not b e e n reported as a sign of overdose or side effect of the m e d i c a t i o n ) We have recently observed 8 young adults with marked hemorrhagic cystitis secondary to consuming "bootleg" methaqualone tablets they obtained from illegal sources. A report of 1 patient with this syndrome is presented. Case Report A seventeen-year-old white male was admitted to the urology service of The Nassau County Medical Center with a chief complaint of pain in the lower region of the abdomen, marked hesitancy, frequency of urination, and gross hematuria, all of four hours' duration. The young man denied experiencing any fever or chills, nausea or vomiting, or prior episodes of a similar nature. Physical examination revealed a blood pressure of 130/70, pulse 72 per minute and regular, and temperature 98.6 F. Pertinent physical findings were confined to the urinary tract. Mild suprapubic tenderness was present without rebound, rigidity, or guarding. No abdominal masses could be felt. There was no eostovertebral angle tenderness. Examination of the prostate gland revealed a 2 plus boggy gland that was slightly tender to palpation. Results of routine laboratory
54
tests were as follows: hemogram, blood urea nitrogen, creatinine, sugar, electrolytes, bleeding and d o t t i n g time, and prothrombin time were all within normal limits. On three separate occasions urine tests for acid fast bacteria and Papanieolaou smears were reported to be negative. Intravenous urogram revealed a normal: upper urinary tract bilaterally. A "tear shape" bladder was seen on the thirty-minute eystogram, and the bladder base appeared to be elevated (Fig. 1). Cystoseopy revealed the presence of a slightly edematous and friable prostatic urethra. The condition of the interior of the bladder, howeverl was alarming; there were areas of marked hemorrhagic cystitis with ulceration and frank necrosis diffusely spread throughout the bladder. Both ureteral orifices were normally shaped and were found to efflux clear urine. Several areas of the bladder were biopsied, with eare taken to obtai~ specimens along the margins of the ulcerated areas. Several days following cystoseopy the results of the urologic studies were reviewed. There was no bacteria present on any of the urine culture studies, including acid fast studies; there were no cytologic findings on routine studies; and a Tine test result was negative. The bladder biop, sies, reported by the pathologist, s h o w e d sec~ tions with areas of degenerating transitiofial epithelium and some fibroeollagenous tissue, small congested capillaries as well as areas of
UROLOGY
/
JANUARY 1974
/ VOLUME III, NUMBER ~
FIGURE 2. Microscopic section showing epithelium completely replaced by debris and neutrophils (arrow); lamina propria also shows similar acute inflammatory cell infiltrate. Smooth muscle layer with interfascicular connective tissue is not unusual.
~iGU~ ?hirty-minute intravenous uro: demot~,~,., ~g normal upper tracts, tear sh, hladd ~::' ~elevation of bladder base.
Z'
.
hemo:~ha:~-'ic necrosis. Infiltration by acute =~:~ ~ubac ili:e iinflammatory cells, p o l y m o r p h o n u c ,a: ympl,~:,,:::ytes, plasma cells, and some lymt: <} ~tes were noted. A diagnosis of acute ulcera r~: ~)stit is wa:!~ made (Fig. 2). : A t this juncture, careful interrogation of u: ~atie~ t who had b e e n made aware of the seri~ ts 6ess ~of h:is condition, revealed the follo~ n? [nfon!:tatio:a: he was a drug user and had in he~ :ast several months experimented with vari u!; rms ot! "downs." Two weeks prior to the ol e : •. ¢• f h!s symp~:oms, he had b e g u n to take boot] g' niethaciualone. This particular pill, he told is. ~huld be purchased illegally from local push, rs. The patient agreed to have his girl friend b: ntg uS a sample. !~ Nassau County toxicologist, S. H. Bidan ~t, M.D., recognized the pill as one of several !i:!,at:: had l:leen found in use in the area in the 1: tst: ~eek. We learned that 7 other teenagers Ilad ~i~peared with the same syndrome. The comr,:~ ~r~ i!:enorninator in all of these cases of hemorrh~t!:ic eystit/s was the use of "bootleg" methaqualol: e In each case the symptoms s e e m e d to app,: ar @ithin six hours after taking the pill. ) T h e patient, after forced hydration and alka dZation of his urine accompanied by the u,,i;q al Nild antiseptics, made a recovery.
~
Comment Methaqualone is a sedative and hypnotic ag,::,nt Whose chemical name is 2-methyl-3-0-to'.Lq4('3H)-quinazolinone. In the synthesis of I::]iis
qtlOLOcy / JANUARY i974 / VOLUME III, NUMBER [
drug, two organic compounds are present, orthoamino benzoie acid and ortho-toluidine 2 aminot o l u e n e 2 0 r t h o - a m i n o benzoic acid does not cause hematuria. Ortho-toluidine, however, may eause hematuria b u t has not b e e n reported to be a cause of bladder tumors. 4 At the International Symposium on Microchemistry, held at Pennsylvania State University, in August, 1973, Mr. John Gunn, of The Bureau of Narcotics and Dangerous Drugs, reported 11 patients with the same syndrome. Analysis of the illegal supply of methaqualone revealed the presence of ortho-toluidine. 5 We conjecture that an attempt to manufacture or synthesize methaqualone for illegal sale was accomplished. The end product, however, contained some percentage of ortho-toluidine. This chemical can cause necrotizing cystitis. This ease brings into focus the need for the urologist to consider chemical factors as an etiologic mechanism of urinary tract symptoms. Certainly in our drug-oriented society this problem may b e c o m e more prevalent. 4760 Sunrise Highway Massapequa Park, New York 11762 (DR. GOLDFARB) References i. INABA, D. S., GAY, G. R., NEWMEYER, J. A., and WHITEHEAD, C.: Methaqualone abuse, J.A.M.A. 224: 1505 (1973). 9,. PASCARELLI, E . F . : Methaqualone abuse, the quiet epidemic, ibid. 224; 1512 (1973). 3. KACHER, Z. H.: Synthesis of methaqualone, Indian J. Chem. Soc. 28:344 (1951). 4. STECI-IER, P. G., Ed.: Merck Index, 8th ed. Rahway, N.J., Merck & Co., Inc., 1968, p. 1059. 5. BIDANSET, J.U.; Personai communication, June, 1 9 7 3 ,
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A B S T R A C T - G r o s s painful hematuria in 8 young adults who consumed "'bootleg" methaqualone (Quaalude) is reported. The cause o f this condition is ortho-toluidine, a compound involved in the synthesis o f methaqualone. A case report and structure o f the lesion is presented.
Methaqualone (Quaalude), "pharmacologically equivalent" to the short and intermediate-acting barbiturates, has entered the arena of desired, and commonly available, drugs of abuse. 1 Urinary tract bleeding has not b e e n reported as a sign of overdose or side effect of the m e d i c a t i o n ) We have recently observed 8 young adults with marked hemorrhagic cystitis secondary to consuming "bootleg" methaqualone tablets they obtained from illegal sources. A report of 1 patient with this syndrome is presented. Case Report A seventeen-year-old white male was admitted to the urology service of The Nassau County Medical Center with a chief complaint of pain in the lower region of the abdomen, marked hesitancy, frequency of urination, and gross hematuria, all of four hours' duration. The young man denied experiencing any fever or chills, nausea or vomiting, or prior episodes of a similar nature. Physical examination revealed a blood pressure of 130/70, pulse 72 per minute and regular, and temperature 98.6 F. Pertinent physical findings were confined to the urinary tract. Mild suprapubic tenderness was present without rebound, rigidity, or guarding. No abdominal masses could be felt. There was no eostovertebral angle tenderness. Examination of the prostate gland revealed a 2 plus boggy gland that was slightly tender to palpation. Results of routine laboratory
54
tests were as follows: hemogram, blood urea nitrogen, creatinine, sugar, electrolytes, bleeding and d o t t i n g time, and prothrombin time were all within normal limits. On three separate occasions urine tests for acid fast bacteria and Papanieolaou smears were reported to be negative. Intravenous urogram revealed a normal: upper urinary tract bilaterally. A "tear shape" bladder was seen on the thirty-minute eystogram, and the bladder base appeared to be elevated (Fig. 1). Cystoseopy revealed the presence of a slightly edematous and friable prostatic urethra. The condition of the interior of the bladder, howeverl was alarming; there were areas of marked hemorrhagic cystitis with ulceration and frank necrosis diffusely spread throughout the bladder. Both ureteral orifices were normally shaped and were found to efflux clear urine. Several areas of the bladder were biopsied, with eare taken to obtai~ specimens along the margins of the ulcerated areas. Several days following cystoseopy the results of the urologic studies were reviewed. There was no bacteria present on any of the urine culture studies, including acid fast studies; there were no cytologic findings on routine studies; and a Tine test result was negative. The bladder biop, sies, reported by the pathologist, s h o w e d sec~ tions with areas of degenerating transitiofial epithelium and some fibroeollagenous tissue, small congested capillaries as well as areas of
UROLOGY
/
JANUARY 1974
/ VOLUME III, NUMBER ~
FIGURE 2. Microscopic section showing epithelium completely replaced by debris and neutrophils (arrow); lamina propria also shows similar acute inflammatory cell infiltrate. Smooth muscle layer with interfascicular connective tissue is not unusual.
~iGU~ ?hirty-minute intravenous uro: demot~,~,., ~g normal upper tracts, tear sh, hladd ~::' ~elevation of bladder base.
Z'
.
hemo:~ha:~-'ic necrosis. Infiltration by acute =~:~ ~ubac ili:e iinflammatory cells, p o l y m o r p h o n u c ,a: ympl,~:,,:::ytes, plasma cells, and some lymt: <} ~tes were noted. A diagnosis of acute ulcera r~: ~)stit is wa:!~ made (Fig. 2). : A t this juncture, careful interrogation of u: ~atie~ t who had b e e n made aware of the seri~ ts 6ess ~of h:is condition, revealed the follo~ n? [nfon!:tatio:a: he was a drug user and had in he~ :ast several months experimented with vari u!; rms ot! "downs." Two weeks prior to the ol e : •. ¢• f h!s symp~:oms, he had b e g u n to take boot] g' niethaciualone. This particular pill, he told is. ~huld be purchased illegally from local push, rs. The patient agreed to have his girl friend b: ntg uS a sample. !~ Nassau County toxicologist, S. H. Bidan ~t, M.D., recognized the pill as one of several !i:!,at:: had l:leen found in use in the area in the 1: tst: ~eek. We learned that 7 other teenagers Ilad ~i~peared with the same syndrome. The comr,:~ ~r~ i!:enorninator in all of these cases of hemorrh~t!:ic eystit/s was the use of "bootleg" methaqualol: e In each case the symptoms s e e m e d to app,: ar @ithin six hours after taking the pill. ) T h e patient, after forced hydration and alka dZation of his urine accompanied by the u,,i;q al Nild antiseptics, made a recovery.
~
Comment Methaqualone is a sedative and hypnotic ag,::,nt Whose chemical name is 2-methyl-3-0-to'.Lq4('3H)-quinazolinone. In the synthesis of I::]iis
qtlOLOcy / JANUARY i974 / VOLUME III, NUMBER [
drug, two organic compounds are present, orthoamino benzoie acid and ortho-toluidine 2 aminot o l u e n e 2 0 r t h o - a m i n o benzoic acid does not cause hematuria. Ortho-toluidine, however, may eause hematuria b u t has not b e e n reported to be a cause of bladder tumors. 4 At the International Symposium on Microchemistry, held at Pennsylvania State University, in August, 1973, Mr. John Gunn, of The Bureau of Narcotics and Dangerous Drugs, reported 11 patients with the same syndrome. Analysis of the illegal supply of methaqualone revealed the presence of ortho-toluidine. 5 We conjecture that an attempt to manufacture or synthesize methaqualone for illegal sale was accomplished. The end product, however, contained some percentage of ortho-toluidine. This chemical can cause necrotizing cystitis. This ease brings into focus the need for the urologist to consider chemical factors as an etiologic mechanism of urinary tract symptoms. Certainly in our drug-oriented society this problem may b e c o m e more prevalent. 4760 Sunrise Highway Massapequa Park, New York 11762 (DR. GOLDFARB) References i. INABA, D. S., GAY, G. R., NEWMEYER, J. A., and WHITEHEAD, C.: Methaqualone abuse, J.A.M.A. 224: 1505 (1973). 9,. PASCARELLI, E . F . : Methaqualone abuse, the quiet epidemic, ibid. 224; 1512 (1973). 3. KACHER, Z. H.: Synthesis of methaqualone, Indian J. Chem. Soc. 28:344 (1951). 4. STECI-IER, P. G., Ed.: Merck Index, 8th ed. Rahway, N.J., Merck & Co., Inc., 1968, p. 1059. 5. BIDANSET, J.U.; Personai communication, June, 1 9 7 3 ,
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