Pancreatitis in Rheumatoid Arthritis and the Role of Systemic AA Amyloidosis in the Pathogenesis of Pancreatitis - A Postmortem Clinicopathologic Study of 161 Patients

The prevalence of pancreatitis is higher in rheumatoid arthritis (RA) than in the general population.
The aim of this study was to determine the prevalence of acute liponecrotic (aLnP), acute relapsing liponecrotic (aRelLnP), and chronic liponecrotic pancreatitis (chrLnP) in RA, and analyze the possible role of systemic and pancreatic AA amyloidosis (sAAa and pAAa) in the pathogenesis of pancreatitis.

Patients and Methods: At the National Institute of Rheumatology 9475 patients died between 1969 and 1992; among them 161 with RA and all of them were autopsied.

RA was confirmed clinically according to the criteria of the American College of Rheumatology (ACR).

Tissue samples of pancreas were available for histologic evaluation in 118 of 161 patients.

Prevalence and histological patterns of pancreatitis were determined at autopsy and characterized histologically. sAAa and pAAa was specified histologically, based on evaluation of 5 organs (heart, lung, liver, kidney and pancreas) in each of the patients.

Demographics of different patient cohorts were compared with the Student (Welch) t-probe. The rerelationship between aLnP, aRelLnP or chrLnP and sAAa or pAAa were analyzed by Pearson’s chi-squared (χ2) test.

Results: Multiple liponecrotic foci (LnP) were found in 15 (12.71 %) of 118 patients; aLnP existed in 8 (53.33 %), aRelLnP in 4 (26.67 %), and liponecrotic foci in combination with chronic fibrotic pancreatitis (chrLnP) in 3 (20.0 %) of these 15 patients.

Systemic AAa complicated RA in 29 (24.58 %) of 118 patients. Amyloid A deposition was detected in blood vessel walls, and on different tissue structures of pancreas in 26 (89.66 %) of 29 cases; in 3 (10.34 %) of 29 patients Amyloid A depositis were not found in the pancreas. In 8 (30.77 %) of 26 patients with pAAa was extreme severe.

Discussion and Conclusions: In elderly female RA patient the risk of LnP was higher comparing those with males or with LnP not associated RA patient, and the elderly female patients with LnP died significantly earlier.

sAAa, as basic complication of RA, may develope in both sexes, and at any time in the course of the disease, and pAAa is closely connected with it.

In essence sAAa not influence the prevalence of pancreatitis, but at higer disease activity, massive amyloid A
deposition in the walls of the pancreatic arterioles, small and medium size arteries can cause local ischemia
and lead to a special form of LnP, namely to aRelLnP (the connection between extreme severe pAAa and
aRelLnP was significant). Marked pAAa should be regarded an important vasculogenic factor in pathogenesis
of aRelLnP, which may be regarded as a special manifestation of autoimmune pancreatitis or a new vasculogenic
entity in RA.

Long term progressive accumulation of amyloid A deposits in the vessel walls and different structures of
the pancreas may be associated with chrLnP, but the connection (link) between pAAa and chrLnP was not
siginificant. This means, that pAAa is only partially responsible for chrLnP, and other reasons should be
considered as well.

Keywords: Rheumatoid arthritis, pancreatitis, systemic and pancreatic AA amyloidosis.