Correspondence

High Serum IgG4 Concentrations in Patients with Sclerosing Pancreatitis

N Engl J Med 2001; 345:147-148July 12, 2001

Article

To the Editor:

Hamano and colleagues (March 8 issue)1 described 20 patients with sclerosing pancreatitis and demonstrated that they had elevated serum IgG4 concentrations. Additional clinical information is needed. Did any of the patients have histologic evidence of the characteristic lymphoplasmacytic inflammation of sclerosing pancreatitis?2 Although this condition is characterized by infrequent attacks of abdominal pain, the symptoms and their duration were not described. How could the response to therapy be distinguished from spontaneous resolution? Can one evaluate a response to a brief course of corticosteroids in a disease that has a chronic course with infrequent attacks? What was the median number of attacks before or after treatment? With respect to the two patients who relapsed, when did the relapses occur?

The point at which IgG4 was initially measured is unclear. Were all measurements made at the height of the flare? There was a significant fall in IgG4 titers after corticosteroid therapy in the group with sclerosing pancreatitis. But the concentrations remained elevated as compared with those in controls. Is this difference significant? Do the concentrations return to normal at a later stage, or will these patients always have abnormal IgG4 titers? The persistence of elevated titers would represent a means by which the disease could be diagnosed in the absence of flare.

Finally, how many patients with chronic pancreatitis were screened to identify the 20 with sclerosing pancreatitis?

Guruprasad P. Aithal, M.R.C.P., Ph.D.
Niall P. Breslin, M.R.C.P.I., M.D.
Bora Gumustop, M.D., M.S.P.H.
Medical University of South Carolina, Charleston, SC 29425
aithalg@musc.edu

2 References

1. 1

   Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732-738
   Full Text | Web of Science | Medline

2. 2

   Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 1991;22:387-395
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Pancreatic tissue was obtained by needle biopsy from 5 of the 20 patients with sclerosing pancreatitis. All tissue specimens showed characteristic features of lymphoplasmacytic inflammation and fibrosis.

Like most patients with sclerosing pancreatitis, our patients reported jaundice. Such patients usually do not have symptoms of an acute attack of pancreatitis, such as severe abdominal pain.1,2 Jaundice caused by swelling of the pancreatic head subsides promptly after treatment with corticosteroids. All our patients were treated with corticosteroids. Patients with spontaneous remission were not included in the study. The response to therapy was evaluated clinically in most patients as a prompt remission of jaundice. Therapy was started within six weeks after presentation. In the two patients with a recurrence of pancreatitis, the relapse occurred after 22 and 26 months.

The serum IgG4 concentrations were determined during the first hospital admission, when the patients were acutely ill. The serum IgG4 concentrations in 12 patients after four weeks of corticosteroid therapy (median, 223 mg per deciliter) were significantly higher than those in 12 age- and sex-matched normal subjects (median, 39 mg per deciliter) (P<0.001 by the Mann–Whitney test). Of the 20 patients in remission, 16 had values above the upper limit of normal (135 mg per deciliter), though their values were not extremely elevated.

Between September 1994 and February 1999, we obtained serum samples from 20 patients with sclerosing pancreatitis and 45 patients with ordinary chronic pancreatitis. We started to identify patients with sclerosing pancreatitis in 1994 after we learned of this disease at a conference.3 We have not screened most patients who have characteristic findings of ordinary chronic pancreatitis.

Shigeyuki Kawa, M.D.
Hideaki Hamano, M.D.
Kendo Kiyosawa, M.D.
Shinshu University School of Medicine, Matsumoto 390-8621, Japan
skawapc@hsp.md.shinshu-u.ac.jp

3 References

1. 1

   Horiuchi A, Kawa S, Akamatsu T, et al. Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: a case report and review of the Japanese literature. Am J Gastroenterol 1998;93:260-263
   CrossRef | Web of Science | Medline

2. 2

   Uchida K, Okazaki K, Konishi Y, et al. Clinical analysis of autoimmune-related pancreatitis. Am J Gastroenterol 2000;95:2788-2794
   CrossRef | Web of Science | Medline

3. 3

   Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality: proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 1995;40:1561-1568
   CrossRef | Web of Science | Medline

Citing Articles (8)

Citing Articles

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   Shigeyuki Kawa, Hideaki Hamano, Yayoi Ozaki, Tetsuya Ito, Ryou Kodama, Yoshimi Chou, Mari Takayama, Norikazu Arakura. (2009) Long-Term Follow-Up of Autoimmune Pancreatitis: Characteristics of Chronic Disease and Recurrence. Clinical Gastroenterology and Hepatology 7:11, S18-S22
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   Antonio M Morselli-Labate, Raffaele Pezzilli. (2009) Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta-analysis. Journal of Gastroenterology and Hepatology 24:1, 15-36
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   Y. Sakaguchi, M. Inaba, M. Tsuda, G. K. Quan, M. Omae, Y. Ando, K. Uchida, K. Okazaki, S. Ikehara. (2008) The Wistar Bonn Kobori rat, a unique animal model for autoimmune pancreatitis with extrapancreatic exocrinopathy. Clinical & Experimental Immunology 152:1, 1-12
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   Sung-Hoon Moon, Myung-Hwan Kim, Do Hyun Park. (2008) Treatment and Relapse of Autoimmune Pancreatitis. Gut and Liver 2:1, 1
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   Lynn D. Cornell, Sonia L. Chicano, Vikram Deshpande, A. Bernard Collins, Martin K. Selig, Gregory Y. Lauwers, Laura Barisoni, Robert B. Colvin. (2007) Pseudotumors due to IgG4 Immune-Complex Tubulointerstitial Nephritis Associated With Autoimmune Pancreatocentric Disease. The American Journal of Surgical Pathology 31:10, 1586-1597
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   Jasjeet S. Sekhon, Raymond T. Chung, Mark Epstein, Marshall M. Kaplan. (2005) Steroid-Responsive (Autoimmune?) Sclerosing Cholangitis. Digestive Diseases and Sciences 50:10, 1839-1843
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   Aideen M. Sullivan, Gerard W. O'Keeffe. (2005) The role of growth/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurones: relevance to Parkinson's disease treatment. Journal of Anatomy 207:3, 219-226
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   Mari Takayama, Hideaki Hamano, Yasuhide Ochi, Hisanobu Saegusa, Kenichi Komatsu, Takashi Muraki, Norikazu Arakura, Yasuharu Imai, Osamu Hasebe, Shigeyuki Kawa. (2004) Recurrent Attacks of Autoimmune Pancreatitis Result in Pancreatic Stone Formation. The American Journal of Gastroenterology 99:5, 932-937
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