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Introduction

  1. Top of page
  2. Introduction
  3. Case Report
  4. Discussion
  5. AUTHOR CONTRIBUTIONS
  6. REFERENCES

Sjögren's syndrome (SS) is a common autoimmune disease, and may occur as an independent entity (primary SS) or in association with a systemic autoimmune disease (secondary SS). Clinically, this syndrome is characterized by diminished lacrimal and salivary gland function. Involvement of the gastrointestinal system, chronic atrophic gastritis in particular, is commonly seen in patients with SS (1). Several reports have noted an 80% incidence rate of chronic atrophic gastritis in patients with SS. However, hypertrophic gastritis in SS has not been reported in the literature. The findings in the case reported here suggest that hypertrophic gastritis may be the initial phenotype of gastritis associated with SS.

Case Report

  1. Top of page
  2. Introduction
  3. Case Report
  4. Discussion
  5. AUTHOR CONTRIBUTIONS
  6. REFERENCES

A 16-year-old male patient was admitted to a county hospital because of a 6-week history of nausea and repeated vomiting with mild abdominal pain and weight loss. No evidence of mechanical ileus was noted. The patient did not report dry mouth or eyes. Endoscopy revealed a diffuse infiltrative mucosal process extending throughout the gastric body and antrum. The gastric rugae were markedly thickened and distorted, with hypomotility of the gastric wall (Figure 1). Endoscopic ultrasonography showed markedly thickened submucosa without evidence of lymphadenopathy. A gastric biopsy sample showed lymphocytic infiltrates and no evidence of lymphoma (Figure 1). The May-Giemsa staining for Helicobacter pylori was negative. Results of a barium meal showed coarse and thickened gastric folds along the antrum and markedly delayed gastric emptying. Despite treatment with intravenous nutrition, H2 blockers, and antiemetics, the patient's condition continued to deteriorate. Newly emerged symptoms included a low-grade fever, watery diarrhea, and knee arthralgia. After 2 weeks, he was transferred to our hospital.

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Figure 1. A, Bilateral parotid enlargement, predominantly on the right side. B, Gastric endoscopy showing markedly thickened and distorted gastric rugae. C, Biopsy sample of labial minor salivary glands revealing focal periductal lymphocytic infiltrate and increased interlobar fibrosis. D, Biopsy sample of lower gastric body showing lymphocytic infiltrate.

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Upon admission, the laboratory examination showed decreased complements (C3: 0.4 gm/liter, C4: 0.1 gm/liter), elevated IgG (24.2 gm/liter), and increased erythrocyte sedimentation rate (47 mm/hour). Peripheral blood cell counts and liver function test results were within the normal ranges. Antinuclear antibody (speckled) was positive, as were antibodies against SSA and SSB. Serum rheumatoid factor and antibodies against double-stranded DNA and single-stranded DNA were negative. Urinary sediment was normal upon microscopic examination, and there was no proteinuria. A scintigraphic study showed no evidence of lymphadenopathy. During the second week of hospitalization, the parotid glands, on the right side in particular, became enlarged (Figure 1). A biopsy sample of the labial minor salivary glands revealed focal periductal lymphocytic infiltrates and interlobar fibrosis (Figure 1). Based on these findings, a diagnosis of primary SS was made. After steroid treatment was initiated (methylprednisolone 80 mg/day), the general condition of the patient improved significantly. Diarrhea and vomiting disappeared. The patient was discharged in 3 weeks. The parotid swelling subsided and the marked gastric fold thickening resolved. The steroid dose was tapered gradually during followup. However, erythema annulare emerged on the face and trunk 3 months later, and 200 mg of hydroxychloroquine daily was added at this point. The patient has now completed a 3-year followup and is free of signs and symptoms.

Discussion

  1. Top of page
  2. Introduction
  3. Case Report
  4. Discussion
  5. AUTHOR CONTRIBUTIONS
  6. REFERENCES

The patient described herein was admitted because of severe vomiting caused by hypertrophic gastritis. Because there was no evidence of malignancy or Helicobacter pylori infection, the gastric abnormality could be attributed to primary SS. This diagnosis was supported by the low fever, arthralgia, annular erythema, parotid gland enlargement, lymphocytic infiltration of the labial minor salivary glands, positive serology, and favorable responses to treatment with corticosteroids and hydroxychloroquine.

Early diagnosis of SS is difficult in many cases because the varied symptoms of SS do not always present at the same time; especially in the early stages, sicca symptoms usually are minimal or absent. Studies of children and adolescents with primary SS have demonstrated that the clinical and immunologic expression differs in various aspects from the disease in adult patients, with a higher frequency of fever, recurrent parotitis, and positive autoantibodies. Therefore, it has been stressed that the classic diagnostic criteria for adult SS, especially sicca syndrome, are not applicable to a pediatric onset of the disease. In contrast, the presence of recurrent parotid swelling and typical laboratory abnormalities can allow the diagnosis of these patients in the early stages (2, 3). The histologic hallmark of SS is a focal lymphocytic infiltration of the exocrine glands, and lip biopsy is still the most accurate test for diagnosis of definitive SS (sensitivity 82–95% and specificity 75–90%). The recurrent salivary gland enlargement has low sensitivity (36.4%) but very high specificity (98.1%) (4). Erythema annulare in anti-SSA–positive patients is recognized as a unique cutaneous manifestation of SS (5, 6).

The most common gastrointestinal manifestation in SS is dysphagia associated with xerostomia. In addition, chronic atrophic gastritis, mild elevation of liver enzymes, primary biliary cirrhosis, sclerosing cholangitis, and subclinical pancreatic diseases have been observed with increased frequency in patients with SS (1). Chronic atrophic gastritis probably accounts for epigastric pain, nausea, and other dyspeptic symptoms seen in patients with SS. According to several previous reports, chronic gastric inflammation with mucosal atrophy was seen in as many as 80% of patients with SS (7–9). In contrast to these studies, Ostuni et al (10) reported that atrophic gastritis was not common among patients with SS, whereas chronic superficial gastritis was seen in most patients. In another study using the Sydney System on the basis of histology, a mild (grade 1) atrophy was present in 25% of patients with SS (11). A moderate (grade 2) atrophy occurred with a frequency of 3%. None of the subjects had severe (grade 3) atrophy. Gastric inflammation, in either the corpus or antrum, was found in 85% of patients with SS. Inconsistency among these studies may be attributed to different stages of the disease. In addition to gastric inflammation, intestinal mucosal inflammation has also been found in patients with SS (12).

Histologically, the main feature of SS is the infiltration of exocrine glands by lymphocytic and plasma cells, resulting in diminished or absent glandular secretion and mucosal dryness. Chronic inflammation is not restricted to lacrimal and salivary glands, and may extend to gastric mucosa. Studies focusing on the histopathology of gastric mucosa are very limited, although achlorhydria, hypopepsinogenemia, and high prevalence of antibodies against gastric parietal cells have been described in the disease (2, 7, 8). Kilpi et al (13) studied mucosal biopsy specimens from 7 patients with primary or secondary SS and found chronic inflammation with mononuclear cell infiltrates and glandular atrophy in all cases. Immunohistochemical staining showed that the cell infiltrates were mainly CD3+ T lymphocytes, and most of the T lymphocytes were CD4+ T cells with a CD4+:CD8+ ratio of 3∼7:1. The composition of the mononuclear cell infiltrate is in agreement with the histologic findings described in the salivary glands of patients with SS.

Previous studies suggest that Helicobacter pylori infection may not be a risk factor of gastritis in SS, although Helicobacter pylori infection is the most common identifiable cause of chronic gastritis in both adults and children, and is strongly associated with atrophic gastritis in adults. First, the prevalence of Helicobacter pylori infection in SS is comparable with that in the general population (11, 14). Second, inflammation caused by Helicobacter pylori infection is commonly superficial, in contrast to the deep infiltration around the glands in gastritis associated with SS. Third, intestinal metaplasia usually develops with Helicobacter pylori–induced gastric mucosa atrophy, but seldom with atrophy in SS. Furthermore, our patient was negative for Helicobacter pylori infection. These data suggest that chronic gastritis in SS is caused by autoimmunity rather than Helicobacter pylori infection.

Atrophic changes in gastric mucosa of patients with SS are age dependent (9). Atrophic gastritis tends to occur in relatively older patients with SS (7, 11), suggesting that the phenotype of gastritis in SS patients may be dependent on the stage of the disease. This dynamic view is indirectly supported by a longitudinal study demonstrating that the glandular atrophy in colonic mucosa progressed over time in a patient with primary SS (12). Moreover, evidence shows that CD4+ T cells mediate the loss of parietal cells and oxyntic gland atrophy (15). In our case, hypertrophic gastritis with mucosal edema and inflammation occurred in a very early stage of SS. We speculate that the lymphocytic infiltration of the gastric mucosa in SS starts as hypertrophic gastritis. As the disruption to the cellular architecture of gastric glands continues, chronic atrophic gastritis eventually emerges.

In conclusion, we suggest hypertrophic gastritis should be added to the list of gastrointestinal manifestations of SS. As such, any patient with symptomatic hypertrophic gastritis accompanied by other evidence of systemic inflammation should be considered for SS evaluation. Treatment of hypertrophic gastritis in such a patient, as in other systemic manifestations of SS, may include corticosteroids.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Introduction
  3. Case Report
  4. Discussion
  5. AUTHOR CONTRIBUTIONS
  6. REFERENCES

Dr. Dai had full access to all of the data in the study and takes responsibility for the integrity of the data.

Study design. Dai.

Acquisition of data. Dai, Han, Li.

Analysis and interpretation of data. Dai, Han, Li.

Manuscript preparation. Dai.

REFERENCES

  1. Top of page
  2. Introduction
  3. Case Report
  4. Discussion
  5. AUTHOR CONTRIBUTIONS
  6. REFERENCES