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Autoimmune pancreatitis: it may be a worldwide entity
GASTROENTEROLOGY 2004;126:1214 –1227
CORRESPONDENCE Readers are encouraged to write letters to the editor concerning articles that have been published in GASTROENTEROLOGY. Short, general comments are also considered, but use of the Correspondence section for publication of original data in preliminary form is not encouraged. Letters should be typewritten and submitted electronically to www.gastro-central.org. Please be sure to send 2 hardcopies of any figures to the editorial office.
Autoimmune Pancreatitis: It May Be a Worldwide Entity Dear Sir: We enjoyed reading the report by Varadarajulu et al.1 on IgG4 levels in patients with idiopathic recurrent pancreatitis. Autoimmune pancreatitis is a fascinating, yet rare type of chronic pancreatitis that resolves with steroid. Therefore, identifying the entity is very important from a clinical aspect. While increasing numbers of cases are being described from Japan and Europe,2 few have been reported in the United States. In Korea, the first case of autoimmune pancreatitis was recognized only after 2002.3 Since then, however, about 30 cases of autoimmune pancreatitis have been described nationwide during the following 2 years. This sudden increment in cases of autoimmune pancreatitis in Korea probably reflects increasing awareness of the entity rather than a rise in the true incidence. This may be analogous to another disease entity of the pancreas, intraductal papillary mucinous tumor (IPMT). When IPMT was first reported in the Japanese literature, many thought that it was a very rare disease that was only reported in Japan. As more physicians recognized IPMT, however, IPMT has become familiar to clinicians all around the world.4 Varadarajulu et al.1 have evaluated the IgG4 levels in 20 patients with idiopathic recurrent pancreatitis and found only 2 patients with elevated IgG4 levels. One plausible explanation for the low rate may be that the population that was evaluated did not contain many cases of autoimmune pancreatitis. Patients with autoimmune pancreatitis rarely complain of the typical severe abdominal pain of pancreatitis and usually visit the hospital due to painless jaundice.5 Other symptoms of autoimmune pancreatitis include nonspecific mild abdominal pain and weight loss. Laboratory studies often show cholestatic profiles of liver dysfunction with only mild elevations of amylase and lipase levels. Many cases, therefore, are suspected as pancreatic cancer but reveal no histologic evidence of cancer. This may differ from the clinical features of the cases evaluated by Varadarajulu et al.1 under the diagnosis of idiopathic recurrent pancreatitis. In our experience, autoimmune pancreatitis rarely presents as idiopathic recurrent pancreatitis, and elevated levels of IgG4 are often discovered in patients who are suspected of pancreatic cancer but have atypical features.6 We believe that autoimmune pancreatitis is not an endemic disease of Japan, and prospect that cases diagnosed as autoimmune pancreatitis will increase as more concern and knowledge grows. KYU-PYO KIM MYUNG-HWAN KIM SANG SOO LEE DONG WAN SEO SUNG KOO LEE Asan Medical Center Gastroenterology Seoul, Republic of Korea 1. Varadarajulu S, Cotton PB. Autoimmune pancreatitis: is it relevant in the west? Gastroenterology 2003;125:1557. 2. Pearson RK, Longnecker DS, Chari ST, Smyrk TC, Okazaki K, Frulloni L, Cavallini G. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas 2003;27:1–13.
3. Kim JY, Chang HS, Kim MH, Choi KS, Kim I, Kang HH, Lee SS, Seo DW, Lee SK, Min YI, Kim JS, Yu ES. A case of autoimmune chronic panreatitis improved with oral steroid therapy. Korean J Gastroenterol 2002;39:304 –308. 4. Farrell JJ, Brugge WR. Intraductal papillary mucinous tumor of the pancreas. Gastrointest Endosc 2002;55:701–714. 5. Okazaki K, Chiba T. Autoimmune related pancreatitis. Gut 2002; 51:1– 4. 6. Kim MH, Kim KP, Lee YJ, Song MH, Park DH, Lee SS, Seo DW, Lee SK, Min YI. 17 Cases of autoimmune chronic pancreatitis. Korean J Intern Med 2003;65(Suppl):S94. doi:10.1053/j.gastro.2004.02.044
Discussion on the North American Study for the Treatment of Refractory Ascites Dear Sir: Sanyal et al. recently reported the results of a multicenter trial comparing the paracentesis with the transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of refractory ascites.1 The study shows a better response of the TIPS treatment but a similar survival. However, the results of the study must be questioned due to severe weaknesses in design and performance. 1. Selection bias The inclusion criteria are not balanced and disfavor the TIPS arm. To avoid renal failure after paracentesis patients were included only when the creatinine concentration was ⬍ 1.5 mg/dL. This is not according to the clinical practice where also patients with a creatinine concentration of ⬎ 1.5 mg/dL are receiving paracentesis if necessary. On the other hand, a bilirubin concentration of up to 5 mg/dL was accepted. What is the creatinine for the paracentesis is the bilirubin for the TIPS treatment. As demonstrated by Chalasani et al.2 a bilirubin concentration of ⬎ 3 mg/dL was closely correlated with mortality (RR: 5.4; 95% CI: 1.4–10.2). This was confirmed by Rajan et al. 3 showing that an elevated pre-TIPS bilirubin level is a powerful independent predictor of 30-day mortality after TIPS creation with a 40% increased risk of death for each 1 mg/dL increase above 3.0 mg/dL. Accordingly, few patients with higher bilirubin levels will increase the mortality in the TIPS arm considerably. What would have been the result if the design of the study was balanced offering a fair comparison of treatments by including either patients with a higher creatinine concentration or a lower bilirubin concentration of, e.g., ⬍ 1.5 mg/dL? In our own study4 the inclusion criteria were more realistic and more balanced (creatinine ⬍ 3 mg/dL, bilirubin ⬍ 5 mg/dL) explaining the different result with a survival benefit for the TIPS patients. The statement by Sanyal et al. that our result was due to the lack of albumin substitution after paracentesis is invalid since only few patients with paracentesis volumes of about 4 liters and normal renal function, who do not benefit from albumin substitution,5 did not receive albumin. Moreover, it is demonstrated that albumin substitution does not effect survival of such patients.6
CORRESPONDENCE Readers are encouraged to write letters to the editor concerning articles that have been published in GASTROENTEROLOGY. Short, general comments are also considered, but use of the Correspondence section for publication of original data in preliminary form is not encouraged. Letters should be typewritten and submitted electronically to www.gastro-central.org. Please be sure to send 2 hardcopies of any figures to the editorial office.
Autoimmune Pancreatitis: It May Be a Worldwide Entity Dear Sir: We enjoyed reading the report by Varadarajulu et al.1 on IgG4 levels in patients with idiopathic recurrent pancreatitis. Autoimmune pancreatitis is a fascinating, yet rare type of chronic pancreatitis that resolves with steroid. Therefore, identifying the entity is very important from a clinical aspect. While increasing numbers of cases are being described from Japan and Europe,2 few have been reported in the United States. In Korea, the first case of autoimmune pancreatitis was recognized only after 2002.3 Since then, however, about 30 cases of autoimmune pancreatitis have been described nationwide during the following 2 years. This sudden increment in cases of autoimmune pancreatitis in Korea probably reflects increasing awareness of the entity rather than a rise in the true incidence. This may be analogous to another disease entity of the pancreas, intraductal papillary mucinous tumor (IPMT). When IPMT was first reported in the Japanese literature, many thought that it was a very rare disease that was only reported in Japan. As more physicians recognized IPMT, however, IPMT has become familiar to clinicians all around the world.4 Varadarajulu et al.1 have evaluated the IgG4 levels in 20 patients with idiopathic recurrent pancreatitis and found only 2 patients with elevated IgG4 levels. One plausible explanation for the low rate may be that the population that was evaluated did not contain many cases of autoimmune pancreatitis. Patients with autoimmune pancreatitis rarely complain of the typical severe abdominal pain of pancreatitis and usually visit the hospital due to painless jaundice.5 Other symptoms of autoimmune pancreatitis include nonspecific mild abdominal pain and weight loss. Laboratory studies often show cholestatic profiles of liver dysfunction with only mild elevations of amylase and lipase levels. Many cases, therefore, are suspected as pancreatic cancer but reveal no histologic evidence of cancer. This may differ from the clinical features of the cases evaluated by Varadarajulu et al.1 under the diagnosis of idiopathic recurrent pancreatitis. In our experience, autoimmune pancreatitis rarely presents as idiopathic recurrent pancreatitis, and elevated levels of IgG4 are often discovered in patients who are suspected of pancreatic cancer but have atypical features.6 We believe that autoimmune pancreatitis is not an endemic disease of Japan, and prospect that cases diagnosed as autoimmune pancreatitis will increase as more concern and knowledge grows. KYU-PYO KIM MYUNG-HWAN KIM SANG SOO LEE DONG WAN SEO SUNG KOO LEE Asan Medical Center Gastroenterology Seoul, Republic of Korea 1. Varadarajulu S, Cotton PB. Autoimmune pancreatitis: is it relevant in the west? Gastroenterology 2003;125:1557. 2. Pearson RK, Longnecker DS, Chari ST, Smyrk TC, Okazaki K, Frulloni L, Cavallini G. Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist? Pancreas 2003;27:1–13.
3. Kim JY, Chang HS, Kim MH, Choi KS, Kim I, Kang HH, Lee SS, Seo DW, Lee SK, Min YI, Kim JS, Yu ES. A case of autoimmune chronic panreatitis improved with oral steroid therapy. Korean J Gastroenterol 2002;39:304 –308. 4. Farrell JJ, Brugge WR. Intraductal papillary mucinous tumor of the pancreas. Gastrointest Endosc 2002;55:701–714. 5. Okazaki K, Chiba T. Autoimmune related pancreatitis. Gut 2002; 51:1– 4. 6. Kim MH, Kim KP, Lee YJ, Song MH, Park DH, Lee SS, Seo DW, Lee SK, Min YI. 17 Cases of autoimmune chronic pancreatitis. Korean J Intern Med 2003;65(Suppl):S94. doi:10.1053/j.gastro.2004.02.044
Discussion on the North American Study for the Treatment of Refractory Ascites Dear Sir: Sanyal et al. recently reported the results of a multicenter trial comparing the paracentesis with the transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of refractory ascites.1 The study shows a better response of the TIPS treatment but a similar survival. However, the results of the study must be questioned due to severe weaknesses in design and performance. 1. Selection bias The inclusion criteria are not balanced and disfavor the TIPS arm. To avoid renal failure after paracentesis patients were included only when the creatinine concentration was ⬍ 1.5 mg/dL. This is not according to the clinical practice where also patients with a creatinine concentration of ⬎ 1.5 mg/dL are receiving paracentesis if necessary. On the other hand, a bilirubin concentration of up to 5 mg/dL was accepted. What is the creatinine for the paracentesis is the bilirubin for the TIPS treatment. As demonstrated by Chalasani et al.2 a bilirubin concentration of ⬎ 3 mg/dL was closely correlated with mortality (RR: 5.4; 95% CI: 1.4–10.2). This was confirmed by Rajan et al. 3 showing that an elevated pre-TIPS bilirubin level is a powerful independent predictor of 30-day mortality after TIPS creation with a 40% increased risk of death for each 1 mg/dL increase above 3.0 mg/dL. Accordingly, few patients with higher bilirubin levels will increase the mortality in the TIPS arm considerably. What would have been the result if the design of the study was balanced offering a fair comparison of treatments by including either patients with a higher creatinine concentration or a lower bilirubin concentration of, e.g., ⬍ 1.5 mg/dL? In our own study4 the inclusion criteria were more realistic and more balanced (creatinine ⬍ 3 mg/dL, bilirubin ⬍ 5 mg/dL) explaining the different result with a survival benefit for the TIPS patients. The statement by Sanyal et al. that our result was due to the lack of albumin substitution after paracentesis is invalid since only few patients with paracentesis volumes of about 4 liters and normal renal function, who do not benefit from albumin substitution,5 did not receive albumin. Moreover, it is demonstrated that albumin substitution does not effect survival of such patients.6