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Symptoms associated with small intestinal involvement in patients with systemic sclerosis (SSc) are usually severe and resistant to treatment.To assess the safety and efficacy of octreotide in refractory small intestinal disease complicating SSc.Seven female patients (aged from 37 to 64 years old) with SSc were included in the study. All of them had symptoms compatible with small bowel pathology, nonresponding to several prokinetic agents. The patients received either subcutaneous octreotide, 0.1 mg twice daily, or intramuscular octreotide LAR (long-acting-release), 20 mg/mo. Symptom severity was assessed at baseline and at various follow-up points in a scale of 0–3, for each symptom. Significant gastrointestinal pathology was excluded by gastroscopy, colonoscopy, and small bowel enemas before octreotide administration.All patients responded to octreotide, and a significant reduction from symptom severity at baseline (mean ± SD: 2.9 ± 1.1) was noted even in the first following month (1.3 ± 0.5, P = 0.0006). A significant disturbance of defecation in 2 patients improved dramatically. Short relapses were noticed in patients who were initially treated with subcutaneous octreotide. These patients were subsequently treated with octreotide LAR, resulting in an overall symptom reduction at 6 months (0.7 ± 0.5, P = 0.003), which was sustained during follow-up (median follow-up: 14.4 months). No side effects were noted.These results suggest that long-term treatment with octreotide LAR may be a safe and effective approach for treatment of small intestinal disease in patients with SSc.