Uomo G. Autoimmune Pancreatitis: An Autonomous Disease or a Single Entity in a Complex Puzzle of a Multi-Organ Disorder?. JOP. J Pancreas (Online) 2010 Mar 5; 11(2):191-192. [Full text]

PANCREAS NEWS

JOP. J Pancreas (Online) 2010 Mar 5; 11(2):191-192.

Autoimmune Pancreatitis: An Autonomous Disease or a Single Entity in a Complex Puzzle of a Multi-Organ Disorder?

Generoso Uomo

Department of Internal Medicine, 'Cardarelli' Hospital. Naples, Italy

Autoimmune pancreatitis is a relatively uncommon, non-alcohol-related form of chronic pancreatitis which has received increasing attention in recent years. In fact, autoimmune pancreatitis represents a "hot topic" in pancreatology, as witnessed by the many reports and extensive recently published reviews [1, 2, 3, 4, 5, 6]. The first report of the disease which dates back to 1961 documented patients who suffered from chronic inflammatory sclerosis of the pancreas associated with hypergammaglobulinemia [7], even if the possibility of an autoimmune mechanism in the pathogenesis of chronic pancreatitis had been already stressed in 1959 [8]. After three decades of single case reports of only limited series of patients with non-alcoholic chronic pancreatitis predominantly associated with chronic inflammatory bowel diseases or sclerosing cholangitis, in 1991, Kawaguchi et al. [9] gave the first detailed description of this special type of pancreatitis and called it "lymphoplasmacytic sclerosing pancreatitis". In 1995, Yoshida et al., reporting a relatively large series from Japan, coined the term autoimmune pancreatitis [10]. Autoimmune pancreatitis is currently recognized as a distinct clinical entity worldwide, identified as a chronic inflammatory condition of the pancreas in which an autoimmune mechanism is involved [6, 11]. High serum IgG4 concentrations have been identified as its distinguishing characteristic and as a marker of autoimmunity as well as of disease activity [12]. The presence of concomitant disorders in other organs together with autoimmune pancreatitis was mainly intended as the proof that the spectrum disease of the pancreas was comparable to that of the bile ducts, liver, colon or salivary glands [13]. Recently, Kamisawa et al. [14] have proposed a novel clinicopathological entity, named "IgG4-related sclerosing disease" (IgG4-RSC) which was based on the histological and immunohistochemical examination of various organs of patients affected by autoimmune pancreatitis. This systemic disease may present different clinical manifestations related to the frequent involvement not only of the pancreas (autoimmune pancreatitis), but also of the bile duct (sclerosing cholangitis, cholecystitis), the salivary gland (sialoadenitis), the retroperitoneum (fibrosis), the kidney (tubulointerstitial nephritis), the lung (interstitial pneumonia), the prostate (prostatitis) and the lymphnodes (lymphadenopathy). Extensive IgG4-positive plasma-cells and T-lymphocyte infiltration of various organs constitutes a common characteristics of this disease. Most of the affected patients present autoimmune pancreatitis at the moment of diagnosis, but pancreatic involvement can be absent [15]; in general, more than two organs are affected, but it is possible to find it in only one of them. The disease occurs more frequently in older men and responds well to corticosteroid treatment. Beginning with the analysis of Japanese patients with IgG4-related disorders, Masaoki et al. [16] have very recently proposed an extension of the IgG4-RSC syndromic complex into a new clinical entity characterized by hyper-IgG4 gammaglobulinemia and IgG4-positive plasma-cell infiltration into the tissue, this being considered an expression of a lymphoproliferative disease ("IgG4-positive multiorgan lymphoproliferative syndrome"; IgG4+MOLPS). In addition to the pathologies considered within the IgG4-RSC group, this syndrome also includes Mikulicz’s disease, Küttner’s tumors, inflammatory pseudotumors (of the lung, liver, and breast), mediastinal fibrosis and autoimmune hypophysitis. IgG4+MOLPS should be differentiated from Sjögren’s syndrome, which presents a similar organ distribution but different clinical-epidemiological-histopathological features and a different autoantibody pattern. Other rare conditions such as multicentric Castelman’s disease and idiopathic plasmacytic lymphoadenopathy should also be considered in differential diagnosis.

These recent papers, based on solid epidemiological, clinical and histopathological features, raise strongly doubts as to autoimmune pancreatitis being considered an autonomous entity and support its classification as a single entity within a multiorgan syndromic complex. At the moment, this working hypothesis may be considered well-grounded only in Eastern populations; studies from Western countries are necessary to confirm this fascinating scenario.

Key words Autoimmune Diseases; Biological Markers; Diagnosis, Differential; Epidemiology

Abbreviations IgG4+MOLPS: IgG4-positive multiorgan lymphoproliferative syndrome; IgG4-RSC: IgG4-related sclerosing disease

Conflict of interest The author has no potential conflicts of interest

Correspondence
Generoso Uomo
Department of Internal Medicine
"Cardarelli" Hospital
via Cardarelli 9
80131 Napoli
Italy
Phone: +39-081.747.2101
Fax: +39-081.747.2117
E-mail: generoso.uomo@ospedalecardarelli.it

References

1. Etemad B, Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 2001; 120:682-707. [PMID 11179244] (FULL TEXT: http://www.gastrojournal.org/article/PIIS001650850100796X/fulltext)

2. Cavallini G, Frulloni L. Autoimmunity and chronic pancreatitis: a concealed relationship. JOP. J Pancreas (Online) 2001; 2:61-8. [PMID 11867865] (FULL TEXT: http://www.joplink.net/prev/200103/1.html)

3. Members of the Criteria Committee for Autoimmune Pancreatitis of the Japan Pancreas Society. Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society. J Jpn Pan Soc 2002; 17:585-7.

4. 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. [PMID 12826899] (FULL TEXT: http://journals.lww.com/pancreasjournal/Fulltext/2003/07000/Controversies_in_Clinical_Pancreatology_.1.aspx)

5. Klöppel G, Lüttges J, Löhr M, Zamboni G, Longnecker D. Autoimmune pancreatitis: pathological, clinical, and immunological features. Pancreas 2003; 27:14-9. [PMID 12826900] (FULL TEXT: http://journals.lww.com/pancreasjournal/Fulltext/2003/07000/Autoimmune_Pancreatitis__Pathological,_Clinical,.2.aspx)

6. Witt H, Apte MV, Keim V, Wilson JS. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology 2007; 132:1557-73. [PMID 17466744] (FULL TEXT: http://www.gastrojournal.org/article/PIIS0016508507004957/fulltext)

7. Sarles H, Sarles JC, Camatte R, Muratore R, Gaini M, Guien C, et al. Observations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis. Gut 1965; 6:545-59. [PMID 5857891]

8. Thal AP, Murray MJ, Egner W. Isoantibody formation in chronic pancreatic disease. Lancet 1959; 1:1128-9. [PMID 13665981]

9. Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N. Lymphopasmacytic sclerosing pancreatitis with cholangitis sclerosing pancreatitis with cholangitis: variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 1991; 22:387-95. [PMID 2050373] (FULL TEXT: http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WGD-4C4FK88-5C-1&_cdi=6820&_user=839424&_pii=0046817791900876&_orig=browse&_coverDate=04%2F30%2F1991&_sk=999779995&view=c&wchp=dGLzVtz-zSkzk&md5=4f53bdc987592c7411ecbfb5884d1e71&ie=/sdarticle.pdf)

10. 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; 40:1561-8. [PMID 7628283] (FULL TEXT: http://www.springerlink.com/content/g5348g2642681707/fulltext.pdf)

11. Okazaki K. Autoimmune pancreatitis: etiology, pathogenesis, clinical findings and treatment. The Japanese experience. JOP. J Pancreas (Online) 2005; 6:89-96. [PMID 15650291] (FULL TEXT: http://www.joplink.net/prev/200501/31.html)

12. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 cncentrations in patients with sclerosing pancreatitis. N Engl J Med 2001; 344:732-8. [PMID 11236777] (FULL TEXT: http://content.nejm.org/cgi/content/full/344/10/732)

13. Okazaki K, Chiba T. Autoimmune related pancreatitis. Gut 2002; 51:1-4. [PMID 12077078] (FULL TEXT: http://gut.bmj.com/content/51/1/1.1.long)

14. Kamisawa T, Okamoto A. IgG4-related sclerosing disease. World J Gastroenterol 2008; 14 3948-55. [PMID 18609677] (FULL TEXT: http://www.wjgnet.com/1007-9327/14/3948.asp)

15. Miura H, Miyaki Y. IgG4-related retroperitoneal fibrosis and sclerosing cholangitis independent of autoimmune pancreatitis. A recurrent case after a 5-year history of spontaneous remission. JOP. J Pancreas (Online) 2009; 10: 432-7. [PMID 19581751] (FULL TEXT: http://www.joplink.net/prev/200907/07.html)

16. Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis 2009; 68:1310-15. [PMID 18701557] (FULL TEXT: http://ard.bmj.com/content/68/8/1310.long)