- Email: [email protected]
Hepatotoxicity associated with piroxicam use
354
CORRESPONDENCE
Second, we prospectively determined the L/A ratio in 32 consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). ERCP is a model of nonalcoholic pancreatitis. Indeed, serum amylase and lipase levels increase after ampulla cannulation. The mechanisms of enzymatic augmentation are probably similar to those observed in biliary pancreatitis. Serum amylase and lipase levels were measured just before, 5 hours after, and the day after ERCP. The L/A ratio was not calculated when serum amylase and lipase values were 11.5N. In 26 patients the diagnosis of choledocolithiasis was suspected; 15 patients actually had choledocolithiasis. The clearance of duct stones was already obtained at the time of ERCP for 11 patients with gallstones in the gallbladder. In the remaining 6 patients, ERCP was performed in 1 case of pancreas divisum, 3 cases of cholangiocarcinoma, and z cases of cholangitis in patients with the acquired immunodeficiency syndrome. Before ERCP, serum amylase and lipase levels were <1.5N in 28 patients. Five hours after ERCP, enzyme levels were increased in 20 patients. In 3 of those patients, enzyme elevation was associated with abdominal pain. There was no relationship between pancreatic duct filling and enzyme levels. Fifteen of the 20 patients had L/A ratios of >2. Furthermore, in this series no patient was alcoholic. The day after ERCP, enzyme levels returned to normal values in 13 patients. Two of 7 patients who still had increased enzyme levels had L/A ratios of 22 (Figure 1). Therefore, in our experience the L/A ratio did not discriminate between alcoholic and nonalcoholic pancreatitis. Indeed many patients (80% and 75% in the retrospective and in prospective studies, respectively] had L/A ratios of >2. We do not recommend using the L/A ratio as a discriminatory index between alcoholic and nonalcoholic pancreatitis.
P. LAURENT-PUIG A. BOUTRON M. J. BRIANTAIS K. VAHEDI J. FRITSCH A. D. CHOURY G. PELLETIER C. BUFFET
Service des Maladies du Foie et de l’appareil Digestif and Laboratoire de Biochimie Hopital Bicetre 78 rue du General Leclerc 94275 Le Kremlin Bicetre Cedex, France
1. Gumaste VV, Dave PB, Weissman D, Messer J. Lipase/amylase ratio: a new index that distinguishes acute episodes of alcoholic from nonalcoholic acute pancreatitis. Gastroenterology 1991;101:1361-1366.
Reply. The conclusion reached by Laurent-Puig et al that the L/A ratio is not a good discriminatory index between alcoholic and nonalcoholic pancreatitis is based on improper analysis of clinical data. First, we must categorically state that not all patients who have asymptomatic elevations of amylase and lipase levels after ERCP have acute pancreatitis. Only patients with significant abdominal pain associated with these laboratory changes can be deemed to have acute pancreatitis. By these criteria, only 3 of the 20 patients studied by Laurent-Puig et al. qualify as having acute pancreatitis. The L/A ratio is relevant in patients with acute pancreatitis. It cannot be applied to patients with asymptomatic elevations of amylase and lipase levels. A well-designed prospective study with strict criteria is needed to resolve this issue.
GASTROENTEROLOGY Vol. 103. No. 1
Addendum: A recently published well-done criteria for the diagnosis of acute pancreatitis findings.
study’ using strict concurs with our
VIVEK GLJMASTE,M.D. PRADYUMAN DAVE, M.D. DOUGLAS WEISSMAN, M.D. JULIO MESSER, M.D. Division of Gastroenterology Mount Sinai Services at the City Hospital at Elmhurst Elmhurst, New York 11373 1. Tenner SM. Steinberg WM. Serum lipase/amylase ratio in alcoholic vs non-alcoholic pancreatitis (abstr). Pancreas 1991; 6:722.
Hepatotoxicity Use
Associated
With Piroxicam
Dear Sir: Hepps et al.’ recently reported a case of piroxicam-associated liver toxicity characterized by severe cholestasis and noted that this is the first such report in the United States. We would like to make you aware of a similar case we reported to the Food and Drug Administration (FDA) in 1987. The patient was a 61-year-old woman who was treated with piroxicam, 20 mg/day orally, for painful left shoulder bursitis. Twelve days after beginning therapy she developed a marked elevation of alanine aminotransferase (ALT) level to >800 IU/L. Her bilirubin level was 118 umol/L (1 mg/dL) at that time. The patient continued to take piroxicam daily during the next 2 weeks and began to develop malaise, anorexia, and generalized pruritus. The ALT level was approximately 1800 IU/L and bilirubin level was ~34 pmol/L (~2 mg/dL). Piroxicam was discontinued, and the ALT level peaked at 2000 IU/L 1 week later. Over the next several weeks a sharp decrease in transaminase levels was noted, but the bilirubin level began rising, peaking 4 weeks later at 342 umol/L (20 mg/dL). The patient was a chronic hepatitis B carrier and did not show evidence of reactivation during this period, as evidenced by absence of hepatitis B core immunoglobulin M antibody. Other viral serological markers were negative, as were autoimmune markers. Ultrasound showed normal gallbladder and pancreas, and the common bile duct was not dilated. The patient was admitted to the hospital for supportive care and discharged to home a few days later. She had slow normalization of bilirubin and transaminase levels, and laboratory values returned to baseline approximately 12 weeks after piroxicam was discontinued. We feel this case represents piroxicam hepatotoxicity that would be classified as mixed cytotoxic and cholestatic according to the criteria described by Zimmerman.’ The relatively few cases like this in the literature suggest that this is an idiosyncratic injury and may depend on immunologic factors or pre-existing metabolic abnormalities in the affected individual.* KENNETH E. SHERMAN, M.D., Ph.D.
Gastroenterology Service Fitzsimons Army Medical Center Aurora, Colorado 80045 CHARLES JONES, M.D. Tripler Army Medical Center Honolulu, Hawaii 1. Hepps KS, Maliha GH, Estrada R, Goodgame R. Severe choles-
tatic jaundice associated 1991;101:1737-1740.
with piroxicam.
Gastroenterology
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z6614nl
CORRESPONDENCE
Second, we prospectively determined the L/A ratio in 32 consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). ERCP is a model of nonalcoholic pancreatitis. Indeed, serum amylase and lipase levels increase after ampulla cannulation. The mechanisms of enzymatic augmentation are probably similar to those observed in biliary pancreatitis. Serum amylase and lipase levels were measured just before, 5 hours after, and the day after ERCP. The L/A ratio was not calculated when serum amylase and lipase values were 11.5N. In 26 patients the diagnosis of choledocolithiasis was suspected; 15 patients actually had choledocolithiasis. The clearance of duct stones was already obtained at the time of ERCP for 11 patients with gallstones in the gallbladder. In the remaining 6 patients, ERCP was performed in 1 case of pancreas divisum, 3 cases of cholangiocarcinoma, and z cases of cholangitis in patients with the acquired immunodeficiency syndrome. Before ERCP, serum amylase and lipase levels were <1.5N in 28 patients. Five hours after ERCP, enzyme levels were increased in 20 patients. In 3 of those patients, enzyme elevation was associated with abdominal pain. There was no relationship between pancreatic duct filling and enzyme levels. Fifteen of the 20 patients had L/A ratios of >2. Furthermore, in this series no patient was alcoholic. The day after ERCP, enzyme levels returned to normal values in 13 patients. Two of 7 patients who still had increased enzyme levels had L/A ratios of 22 (Figure 1). Therefore, in our experience the L/A ratio did not discriminate between alcoholic and nonalcoholic pancreatitis. Indeed many patients (80% and 75% in the retrospective and in prospective studies, respectively] had L/A ratios of >2. We do not recommend using the L/A ratio as a discriminatory index between alcoholic and nonalcoholic pancreatitis.
P. LAURENT-PUIG A. BOUTRON M. J. BRIANTAIS K. VAHEDI J. FRITSCH A. D. CHOURY G. PELLETIER C. BUFFET
Service des Maladies du Foie et de l’appareil Digestif and Laboratoire de Biochimie Hopital Bicetre 78 rue du General Leclerc 94275 Le Kremlin Bicetre Cedex, France
1. Gumaste VV, Dave PB, Weissman D, Messer J. Lipase/amylase ratio: a new index that distinguishes acute episodes of alcoholic from nonalcoholic acute pancreatitis. Gastroenterology 1991;101:1361-1366.
Reply. The conclusion reached by Laurent-Puig et al that the L/A ratio is not a good discriminatory index between alcoholic and nonalcoholic pancreatitis is based on improper analysis of clinical data. First, we must categorically state that not all patients who have asymptomatic elevations of amylase and lipase levels after ERCP have acute pancreatitis. Only patients with significant abdominal pain associated with these laboratory changes can be deemed to have acute pancreatitis. By these criteria, only 3 of the 20 patients studied by Laurent-Puig et al. qualify as having acute pancreatitis. The L/A ratio is relevant in patients with acute pancreatitis. It cannot be applied to patients with asymptomatic elevations of amylase and lipase levels. A well-designed prospective study with strict criteria is needed to resolve this issue.
GASTROENTEROLOGY Vol. 103. No. 1
Addendum: A recently published well-done criteria for the diagnosis of acute pancreatitis findings.
study’ using strict concurs with our
VIVEK GLJMASTE,M.D. PRADYUMAN DAVE, M.D. DOUGLAS WEISSMAN, M.D. JULIO MESSER, M.D. Division of Gastroenterology Mount Sinai Services at the City Hospital at Elmhurst Elmhurst, New York 11373 1. Tenner SM. Steinberg WM. Serum lipase/amylase ratio in alcoholic vs non-alcoholic pancreatitis (abstr). Pancreas 1991; 6:722.
Hepatotoxicity Use
Associated
With Piroxicam
Dear Sir: Hepps et al.’ recently reported a case of piroxicam-associated liver toxicity characterized by severe cholestasis and noted that this is the first such report in the United States. We would like to make you aware of a similar case we reported to the Food and Drug Administration (FDA) in 1987. The patient was a 61-year-old woman who was treated with piroxicam, 20 mg/day orally, for painful left shoulder bursitis. Twelve days after beginning therapy she developed a marked elevation of alanine aminotransferase (ALT) level to >800 IU/L. Her bilirubin level was 118 umol/L (1 mg/dL) at that time. The patient continued to take piroxicam daily during the next 2 weeks and began to develop malaise, anorexia, and generalized pruritus. The ALT level was approximately 1800 IU/L and bilirubin level was ~34 pmol/L (~2 mg/dL). Piroxicam was discontinued, and the ALT level peaked at 2000 IU/L 1 week later. Over the next several weeks a sharp decrease in transaminase levels was noted, but the bilirubin level began rising, peaking 4 weeks later at 342 umol/L (20 mg/dL). The patient was a chronic hepatitis B carrier and did not show evidence of reactivation during this period, as evidenced by absence of hepatitis B core immunoglobulin M antibody. Other viral serological markers were negative, as were autoimmune markers. Ultrasound showed normal gallbladder and pancreas, and the common bile duct was not dilated. The patient was admitted to the hospital for supportive care and discharged to home a few days later. She had slow normalization of bilirubin and transaminase levels, and laboratory values returned to baseline approximately 12 weeks after piroxicam was discontinued. We feel this case represents piroxicam hepatotoxicity that would be classified as mixed cytotoxic and cholestatic according to the criteria described by Zimmerman.’ The relatively few cases like this in the literature suggest that this is an idiosyncratic injury and may depend on immunologic factors or pre-existing metabolic abnormalities in the affected individual.* KENNETH E. SHERMAN, M.D., Ph.D.
Gastroenterology Service Fitzsimons Army Medical Center Aurora, Colorado 80045 CHARLES JONES, M.D. Tripler Army Medical Center Honolulu, Hawaii 1. Hepps KS, Maliha GH, Estrada R, Goodgame R. Severe choles-
tatic jaundice associated 1991;101:1737-1740.
with piroxicam.
Gastroenterology
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