Silica Exposure and Scleroderma: More Bridges and Collaboration between Disciplines Are Needed.

To the Editor:

We have read with great interest Turner and colleagues’ correspondence concerning connective tissue disease (CTD) and silica exposure in artificial stone workers (1). We totally support their call for a new awareness on silica hazards and their broadening to CTD. Indeed, silica hazards are too often, and almost systematically, narrowed to silicosis (2).

Although L. D. Erasmus was historically the first to link silica exposure with the occurrence of systemic sclerosis (SSc or scleroderma), B. Bramwell, a Scottish physician, had described an outbreak of scleroderma among stonemasons 50 years before (3). Despite this ancient association, SSc is still largely considered today to be of unknown cause. The Pasteurian paradigm (one cause, one disease) may have contributed to an oversimplified vision of causality in diseases, leading to a dichotomous vision of etiologies: either an obvious and single cause for some diseases (especially communicable diseases) or complex diseases with too many causal factors to be properly captured. Nonetheless, recent insights into the pathogenesis of SSc, including cancer-associated SSc, remind us that the search for a cause may not be totally in vain. Indeed, when silica exposure is properly explored (i.e., prospectively assessed through dedicated occupational questionnaires and/or evaluation by experts in occupational medicine and toxicology), this exposure appears to be strikingly frequent in male patients with SSc, with at least half of them having occupational silica exposure in recent European studies (4). Therefore, crystalline silica exposure may be a decisive cause or trigger, and this would be especially relevant in males, who are more often engaged in occupations involving silica. Interestingly, recent insights into the pathogenesis of silica-induced autoimmunity in mouse models have highlighted that the production of autoantibodies after silica exposure was significantly higher in males in comparison with female littermates (5). In humans, sex and gender in SSc may be especially crucial, as SSc is frequently more severe in men.

The current outbreak of silicosis and CTD after exposure to high-silica-content artificial stone dusts both demonstrates the specificity of the association of crystalline silica with autoimmunity in comparison with other mineral dusts and reminds us that silica exposure does not only concern the mining industry but also covers a wider range of sectors. In this regard, the call for systematic screening of patients for CTDs after silica exposure appears central in patients both with and without signs of silicosis and/or pulmonary involvement. Concerning SSc, the systematic screening strategy proposed for a very early diagnosis of SSc (known as VEDOSS [Very Early Diagnosis of Systemic Sclerosis]) (6) may be especially relevant for these silica-exposed patients. This VEDOSS strategy does not only include testing for antinuclear antibodies but also emphasizes the central role of capillaroscopic findings and clinical detection of “puffy fingers,” a manifestation of SSc that may precede the occurrence of sclerodactyly. Such a screening would therefore imply a close collaboration of clinicians who have been trained to detect puffy fingers or other SSc early signs and who are familiar with capillaroscopic examinations with specialists of occupational diseases and silica-associated respiratory disorders likely to detect the situations of silica exposure.

Beyond preventability and diagnosis, the lack of a proper understanding of the pathogenesis of silica-associated autoimmunity may also result from missing bridges between disciplines. From a toxicant viewpoint, this question of silica has been almost exclusively studied through fibrotic pulmonary diseases or cancer or, when addressing autoimmunity, has been based on mouse models of systemic lupus, whereas SSc has long been considered the CTD most frequently associated with silica exposure. The alarming recent outbreak of silica-associated CTD may provide an opportunity to fill this gap and offer a timely lever to collectively better understand the pathogenesis of SSc.