From silicosis to sarcoid-like reaction: a continuum model of silica-induced lung disease
Year: 2026
Type: review
Abstract: The term “sarcoidosis”, coined in 1899 from the Greek sarx (flesh) and - oid (resembling), is descriptive and conveys no aetiological information. When a trigger has been identified for a granulomatous condition previously considered idiopathic, nomenclature has tended to shift from descriptive to aetiological, as when “Salem sarcoid” was reclassified as chronic beryllium disease (CBD). Crystalline silica exposure has been associated with sarcoidosis in several occupational cohorts, and partially overlapping immunopathogenic pathways have been described, notably NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and T-helper cell 17.1 (Th17.1) polarisation, neither of which is disease-specific. The available evidence is consistent with a continuum model of silica-induced lung disease spanning a silicotic fibrotic phenotype (classical silicosis, driven by NLRP3 and transforming growth factor-β1 signalling), a granulomatous phenotype (silica-induced sarcoid-like reaction (SISLR), driven by NLRP3, interleukin-1β and Th17.1 signalling in susceptible individuals) and a mixed phenotype in which both processes coexist. The silica lymphocyte proliferation test (Si-LPT) has detected in vitro immunoreactivity in a subset of patients with sarcoidosis but is not standardised. The CBD paradigm offers useful analogies, although beryllium-driven adaptive and silica-driven innate mechanisms differ in important respects. SISLR may serve as a working classification that identifies the putative trigger, supports occupational disease recognition and situates the granulomatous response within a broader continuum; we discuss it alongside the alternative “silicosarcoidosis” terminology. On the evidence reviewed, crystalline silica should no longer be treated as an incidental co-exposure in a patient with sarcoid-type granulomas. A documented exposure warrants classification as occupationally related granulomatous lung disease and standardising the Si-LPT is the immediate priority.
Source: European Respiratory Review
Authors: Metin Akgün, Alperen Aksakal, Ozlem Kar Kurt
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225258701