18 Pancreatic Disease in Sjögren’s Syndrome and IgG4-Related Disease |
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Table 18.1 Clinical characteristics of Sjögren’s syndrome and IgG4-related disease (IgG4-RD)
|
Sjögren syndrome |
IgG4-RD |
Sex predominance |
Female |
Male |
Gland swelling |
Recurrent |
Persistent |
Keratoconjunctivitis sicca |
Mild to severe |
None to slight |
Gland function |
Impaired |
Normal |
Response to glucocorticoid |
Not significant |
Significant |
Antinuclear antibody |
Positive, high titer |
Positive, low titer |
Anti-Ro/La antibodies |
Present |
Not present |
Elevated serum IgG4 |
None |
Most cases |
Gland pathology |
Presence of severe lymphocytic |
Infiltration of abundant IgG4+ |
|
infiltration with no IgG4+ |
plasma cells and fibrosis |
|
plasma cells |
|
18.3Involvement of the Pancreas in SjS
18.3.1Clinical Presentation
The pancreas secretes approximately 1.5 L of enzyme-rich fluid every day for the digestion of fats, carbohydrates, and protein. Advanced pancreatic exocrine insufficiency results in maldigestion of fat and protein leading to steatorrhea and weight loss. Although subtle changes in exocrine function can be detected in patients with early pancreatic disease, overt steatorrhea does not occur until approximately 90% of glandular function has been lost [14]. Patients with mild pancreatic exocrine insufficiency may have subclinical maldigestion and normal appearing bowel movements, although latent fat-soluble vitamin deficiencies may be detected.
Pancreatic manifestations in patients with SjS are diverse. In a large series of patients with primary SjS, the prevalence of acute pancreatitis of any etiology was reported to be 0.5% [15]. Acute pancreatitis is reported less frequently than chronic pancreatitis in the medical literature [2], but there is no information available on the prevalence of chronic pancreatitis in these patients. The clinical presentation of acute pancreatitis, associated with abdominal pain, nausea, and vomiting, is uncommon in SjS patients.
Abnormal exocrine pancreatic function has been documented in up to one third of patients with SjS [16], but this usually remains subclinical. Patients with SjS rarely suffer from maldigestion or steatorrhea. Several studies have investigated pancreatic exocrine function in SjS [5, 17–23]. In these studies, various diagnostic tests have been used to evaluate pancreatic exocrine function. The results of these tests are variable and are mainly useful for detecting cases of advanced pancreatic failure, not subtle dysfunction. The pancreatic function studies in SjS have shown variable and sometimes discordant results. The findings have varied from an absence of involvement [5], to minimum involvement [19] or involvement in up to 30% of patients [16, 18].
One recent study performed in the post-IgG4-RD era evaluated pancreatic function of 12 SjS patients combining the secretin test and magnetic resonance cholangiography (MRCP). This study showed up to 80% of patients had normal exocrine function and 100% had normal duodenal filling [24].
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The endocrine function of the pancreas seems to be unaffected by SjS. The frequency of type 2 diabetes mellitus in patients with primary SjS is higher than in age-matched controls, but this may be a function of several factors, particularly increased glucocorticoid use, decreased antimalarial use, and higher body mass index among patients with both SjS and type 2 diabetes compared to those with SjS alone [24, 25]. In summary, slightly reduced exocrine function is the most common pancreatic abnormality in patients with SjS, but this finding has little clinical consequence for patients in most cases.
18.3.2Autoantibodies
The presence of antibodies to pancreatic antigen and pancreatic duct cells has been demonstrated in patients with SjS [16, 26]. Pancreatic duct autoantibodies were detected in the sera of patients with SjS who had abnormal exocrine pancreatic function [27]. One study showed that the sera from patients with SjS who had antibodies against salivary duct epithelial cells also had a positive intraand interlobular immunofluorescence reaction to human and monkey pancreatic duct cells. These sera also demonstrated positive staining in parotid, submandibular, and lacrimal tissue from healthy controls, suggesting the presence of a common antigen in the studied organs [28]. The presence of these antibodies and autoreactivity does not imply that they are pathogenic. In theory, chronic glandular inflammation and antigen exposure may lead to the production of nonspecific antibodies that react to similar exocrine gland tissues, namely, the salivary gland and pancreas.
18.3.3Pancreatic Enzymes
Patients with systemic lupus erythematosus and SjS are known to have elevated pancreatic enzymes in some cases. One study showed that 24% of patients with SjS had hyperamylasemia of isotypes P and S. However, these patients did not have any clinical symptoms of pancreatitis [29]. Higher values of trypsinogen have also been documented in these patients [17]. On the other hand there are reports of reduced amylase and/or lipase in the pancreatic juice in patients with SjS, which is consistent with exocrine hypofunction [24].
18.3.4Pathology
There are few pathologic descriptions of pancreatic pathology in SjS. Furthermore, as alluded to earlier in this chapter, it is likely that many of the reports that document involvement of the pancreas in SjS, in hindsight, actually represent IgG4-RD.