Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis

Abstract

To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.