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.

Association of occupational exposure with features of systemic sclerosis

“…Few series have assessed the association between autoantibody status and occupational exposure in SSc, and the results were divergent. 8,[17][18][19][20][21][22] This study demonstrates a relationship between anti-Scl 70 antibody and exposure to solvents, and a negative correlation with anticentromere antibody; there was no correlation between both anti-RNA polymerase III and anti-Th/To antibodies and exposure to silica/solvents in patients with SSc.…”

Mortality study of gold miners exposed to silica and nonasbestiform amphibole minerals: An update with 14 more years of follow‐up

“…Categories which showed marked excesses here, but which were not revealed by underlying cause analysis, included arthritis, other musculoskeletal disease (including lupus and sclerosis), other diseases of the skin (including scleroderma and lupus), alcoholism, other diseases of the blood-forming organs, and other myocardial degeneration. Several of these disease (lupus, scleroderma, systemic sclerosis, rheumatoid arthritis) are autoimmune diseases, and are known to be associated with silica [Rustin et al, 1990;Haustein et al, 1990; Koskela et al, 1987; Sluis-Cremer et a]., 1985; Klockars et al, 19871. The cardiovascular disease elevations revealed by multiple cause analyses may have been due to the effects on the circulatory system of the pneumoconiotic lung disease which was so prevalent in this cohort.…”

Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours

“…Rheumatic silicosis is known as 'Caplan's syndrome' [ 171, and an association of autoimmune diseases with silica exposure has long been recognized. Rustin et al [23] attempted to demonstrate the differences between PSS in the patients with silicosis and idiopathic progressive sclerosis, and no clinical, immunological or serological differences were detected between the two types of sclerosis. In previous papers [9,24], we reported a finding of polyclonal human T cell activation by silicate as a superantigen in virro.…”