16.1Dysphagia

Fig. 16.1 Esophageal candidiasis in a 53-year-old woman with Sjögren’s syndrome, limited systemic sclerosis, and primary biliary cirrhosis (Reynolds’ syndrome)

which was associated with GER. The study found slow acid clearance in the esophagus of SS patients with GER suggesting a prolonged duration of reflux. This extended exposure of the esophagus to refluxed acid may result either from defective acid neutralization by salivary bicarbonates or to altered esophageal motility [13–16]. Ho et al. [17] described a high frequency of tertiary waves in patients with markedly abnormal pH that correlated with the total reflux time, suggesting a relationship between these contractions and prolonged exposure of the esophageal mucosa to low pH values.

16.3Chronic Gastritis

Although earlier reports described chronic gastric inflammation with mucosal atrophy in nearly 80% of patients with SS [18–20], the prevalence of chronic gastritis has not been evaluated in recent series. In clinical practice, patients frequently complain of gastric pain, but gastroscopic studies generally reveal only mild abnormalities such as mild atrophic changes in the antrum [21].

Two recent studies have analyzed the prevalence and clinical significance of antiparietal cell gastric antibodies (anti-PCA) in primary SS. Nardi et al. [22] found positive anti-PCA antibodies in 90 (27%) out of 335 patients. These patients showed a higher prevalence of thyroiditis and autoimmune liver involvement, but not gastrointestinal involvement. El Miedany et al. [23] found anti-PCA antibodies in one third of SS patients and controls. However, all SS patients with anti-PCA antibodies had Helicobacter pylori infection, in comparison with less than half of the autoantibody positive controls. Likewise, only 22% of the autoantibody positive controls

Fig. 16.2 Gastritis (H. pylori infection+) in a patient with primary SS with dyspepsia

had atrophic changes in gastric mucosa compared with 86% of those with SS. This study found a close association between anti-PCA antibodies and H. pylori infection, suggesting that this bacterium may induce a local hyperreactive/autoimmune response that facilitates the induction of autoantibodies against the gastric mucosa of SS patients.

Although anti-PCA antibodies have been associated with chronic atrophic gastritis and pernicious anemia, the two processes are only rarely described in patients with primary SS. Two cases were described in a recent review of hematologic manifestations in a cohort of 380 SS patients [24], with only four additional cases being reported [25–27], suggesting that chronic atrophic gastritis and pernicious anemia are very infrequent in primary SS.

16.4Helicobacter pylori Infection

A number of studies have analyzed the prevalence and clinical significance of H. Pylori infection in primary SS, searching for a possible association with dyspepsia, gastritis (Fig. 16.2), gastric ulcers, or lymphoma, with controversial results. Sorrentino et al. [28] and Theander et al. [29] found that SS patients have H. pylori seroprevalence rates that are similar to those of controls, while Collin et al. [21] found that the seroprevalence of H. pylori infection in dyspeptic SS patients was similar to that of dyspeptic patients without SS. In contrast, other studies have described a higher prevalence of H. pylori antibodies in primary SS compared with controls [30–32]. El Miedany et al. [23] found both a significantly higher prevalence and higher serum titers of IgG and IgM anti-H. pylori antibodies in SS patients

compared with both patients with other autoimmune diseases without sicca syndrome and healthy controls. This might reflect geographical differences in the prevalence of H. pylori infection, which is reported to be lower in Sweden than in other countries. Moreover, a recent study has shown that H. pylori was detected in gastric biopsies in 71% of Italian SS patients in comparison with 31% of Scandinavian patients [29].

The histological severity of gastritis has been associated closely with the presence of H. pylori in primary SS. However, a recent study showed that eradication of H. pylori caused a significant regression of gastric MALT and atrophy in controls but not in SS patients [33]. In addition, dyspepsia did not improve following bacterial eradication in the majority of SS patients, suggesting that H. pylori does not play a role in the dyspeptic symptoms found in SS.

A possible relationship between H. pylori and gastric lymphomagenesis in SS has recently been postulated. Lymphoid accumulation in the gastric mucosa is common in SS but full evidence for an antigen-driven B-cell expansion has not been demonstrated. De Vita et al. [30] described a low-grade gastric lymphoma concomitantly with H. pylori infection in a patient with SS. After H. pylori eradication, a dramatic regression of gastric lymphoma into chronic gastritis was observed, but no amelioration occurred in the parotid and nodal involvement. Multiple molecular analyses showed the expansion of the same B-cell clone in synchronous and metachronous lymph node, parotid, and gastric lesions before and after H. pylori eradication. Ferraccioli et al. [34], who studied the gastric tissue in SS in order to define whether the presence of MALT in the stomach is associated with several infectious agents, showed that H. pylori infection is not more frequent among patient with SS than in controls, and that the abnormal accumulation of MALT may occur in the stomach even in the absence of H. pylori infection. Other studies performed on a limited number of SS patients with simple dyspepsia indicate that clonality may persist for up to 6 months after the eradication of H. pylori [35]. Thus, although H. pylori may play a crucial role in the local boosting of B-cell lymphoproliferation, the underlying B-cell disorder seems to be a nonmalignant process [30].

16.5Association with Celiac Disease

Recent studies have analyzed the potential association between primary SS and celiac disease in small series of patients. In the general population, the prevalence of celiac disease is estimated to be 0.45%. Iltanen et al. [36] found that 5 (15%) out of 34 SS patients had celiac disease, while Szodoray et al. [37] diagnosed celiac disease in 5 (4.5%) out of 111 patients with SS. In contrast, Lazarus and Isenberg [38] found 1 (0.9%) patient with celiac disease out of 114 individuals with primary SS, and another series of 400 SS patients detected not a single celiac disease case [39].