Abstract

Background
Sarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.

Objective
To investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosis

Methods
We retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.

Results
We included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).

Conclusions
Our study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

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Comments

An interesting study of the relationship between exposures and the site of sarcoid involvement. Lung only sarcoidosis associated with silica and metal exposures (inorganic dusts) and organic dusts suggesting an inhalational route for the the association. Liver and spleen involvement was associated with livestock and humans (healthcare, teaching) perhaps suggesting a microbial association (or ingested?). Cardiac sarcoidosis was associated with reactive chemical exposures (isocyanates, acrylates, epoxy resins). The numbers here were small but reactive chemicals bind with body proteins to produce neo-antigens. Smokers were more likely to have eye involvement (a mystery). This study could only have been done in a centre screening all patients with sarcoidosis for extrathoracic involvement, and taking an occupational history, something we should all be doing.

8/11/2021