Prevalence and predictive factors of osteoporosis in systemic sclerosis patients: a case-control study.

PURPOSE: Investigate the prevalence of osteoporosis in patients with systemic sclerosis (SSc) and describe alterations of bone tissue with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT). METHODS: Thirty-three patients and 33 controls matched on age, body mass index (BMI) and menopause were included. Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry. Volumetric BMD (vBMD) and bone microarchitecture were measured by HR-pQCT at tibia and radius. RESULTS: In patients, BMI was significantly lower, the prevalence of osteoporosis was significantly higher and HR-pQCT analysis showed a significant alteration of the trabecular compartment with a decrease in trabecular vBMD on both sites than in controls. In multivariate analysis, a low lean body mass, presence of anticentromere antibodies and older age were identified as independent factors for decreased BMD at LS (r²=0.43), FN (r²=0.61) and TH (r²=0.73). History or current digital ulcers were also identified as an independent factor for microarchitecture alteration. CONCLUSIONS: In patients an increased prevalence of osteoporosis was found and HR-pQCT showed impaired trabecular bone compartment. Also, low lean body mass, high age, digital ulcers and ACAs were identified as independent risk factors for bone damage.

Gastrointestinal manifestation of systemic sclerosis--thickening of the upper gastrointestinal wall detected by endoscopic ultrasound is a valid sign.

OBJECTIVE: Gastrointestinal (GI) tract involvement has been observed in the majority of patients with SSc. This has been attributed to an accumulation of extracellular matrix within the GI walls. We visualized the walls of the oesophagus, stomach and duodenum with its layers and measured the thickness in SSc patients and control patients utilizing endoscopic ultrasound (EUS). METHODS: Twenty-five SSc patients and 25 controls were evaluated. In addition to analysis of clinical symptoms, endoscopy and EUS (20-MHz miniprobe) were performed. The thickness of the complete wall was measured, and the mucosa, submucosa and muscularis were evaluated separately. RESULTS: Clinical symptoms of SSc patients were dysphagia (14/25) and heartburn (19/25). Endoscopic findings were hiatal hernia (16/25), oesophagitis (6/25), amotility (19/25) and a dehiscent pylorus (15/25). In comparison with controls, SSc patients had significantly thicker oesophageal [SSc 1.619 (0.454) mm, control 1.392 (0.333) mm; P = 0.025], antral [SSc 1.876 (0.635) mm, control 1.599 (0.291) mm; P = 0.029] and duodenal [SSc 1.730 (0.522) mm, control 1.525 (0.222) mm; P = 0.039] walls. Predominantly, submucosa and muscularis were significantly thicker in SSc patients. The presence of dysphagia or amotility was significantly associated with the thickening of the GI walls. CONCLUSIONS: The EUS revealed a significant thickening of the walls of the upper GI tract in SSc patients. Predominantly, the submucosa and muscularis are enlarged. These results strengthen the hypothesis that increased matrix deposition is an important aspect in the pathogenesis of GI involvement in SSc.

Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis.

OBJECTIVE: Although gastrointestinal tract dysfunction is a common feature in patients with systemic sclerosis (SSc; scleroderma), few studies have addressed the pathogenetic mechanisms of gastrointestinal tract involvement in SSc. We previously showed that severe fibrosis and increased expression of profibrotic cytokines are important hallmarks in the gastric wall of patients with SSc. The aim of the present study was to investigate whether immune and/or microvascular abnormalities may account for tissue damage in gastric wall specimens obtained from patients with SSc. METHODS: Gastric biopsy samples from 27 patients with SSc and 15 healthy control subjects were analyzed by immunohistochemistry for CD45/leukocyte common antigen, CD3/T cells, CD4/T helper cells, CD8/cytotoxic T cells, CD20/B cells, CD14/monocytes, CD68/macrophages, cell adhesion molecules CD11a/lymphocyte function-associated antigen 1 (LFA-1), CD49d/very late activation antigen 4 (VLA-4), CD54/intercellular adhesion molecule 1 (ICAM-1), CD106/vascular cell adhesion molecule 1 (VCAM-1), CD31/platelet endothelial cell adhesion molecule 1, and vascular endothelial growth factor (VEGF). RESULTS: T cell infiltration was a prominent finding in gastric specimens from patients with SSc. The CD4+/CD8+ T cell ratio was significantly increased in SSc specimens compared with controls. T cells were found in both lymphocyte aggregates and diffuse infiltrates and strongly expressed the activation markers VLA-4, LFA-1, and ICAM-1. Endothelial cells showed corresponding surface activation with strong expression of VCAM-1 and ICAM-1. Mature B cells were frequently observed arranged in aggregates and rarely were seen in a diffuse pattern. Most lymphocyte aggregates lacked monocyte/macrophages. No difference in microvascular density was observed between SSc specimens and controls. Both SSc and control specimens showed weak or no expression of VEGF. CONCLUSION: Our findings provide the first evidence that endothelial/lymphocyte activation leading to prominent CD4+ T cell infiltration may play a key pathogenetic role within the gastric wall of patients with SSc and may represent an important therapeutic target.