Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients

Abstract

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients.In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD.In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0-18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25-80) yrs. Berylliumcontaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard.In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.

Etiologies of Sarcoidosis

“…Genetic variants of other immune response genes such as TNF may also influence risk of developing CBD [61]. Since CBD is a known cause of chronic granulomatous lung disease, occupational health screening and immunological testing should be utilized when appropriate [62]. A recent publication of an experimental model of CBD recapitulates many of the features found in human disease, providing a new tool to help understand the pathogenic mechanism of granulomatous lung disease involved in CBD and sarcoidosis [63].…”

Pathogenesis of sarcoidosis

“…In addition, phenotyping of patients often requires a long-term follow-up because a considerable percentage of patients presenting initially with acute disease and apparent good prognosis might subsequently develop chronic sarcoidosis with severe organ damage later on [56,57]. Moreover, the fact that environmental [51] and occupational [58] exposures may cause phenocopies of sarcoidosis such as life guard lung and chronic beryllium disease complicates any genetic analysis. Nonetheless, subgrouping of patients according to specific clinical features and phenotypes of disease will in future studies most likely increase the ability to identify new genes of importance for sarcoidosis.…”

“…Moreover, SAA serves as a ligand for TLR2 and other receptors of innate immunity which stimulates macrophages and T-cells [105]. Next to PAMPs, anorganic substances like beryllium [58], crystalline silica [31] and other anorganic compounds are capable of inducing granulomatous immune responses, which cannot be distinguished from sarcoidosis. Since sarcoidosis is a very heterogeneous disorder, it can be assumed that not only one but several etiological agents may induce the characteristic Th1-hyperreactivity.…”

The Diagnosis of Sarcoidosis

“…Chronic beryllium disease can be misdiagnosed as sarcoidosis in up to 40% of cases according to 1 series. 15 Exposure to beryllium can occur in diverse industries, for example, aerospace, automotive, biomedical (dental), x-ray tubes manufacturing, defense, and telecommunications (see ref 16 for comprehensive listing of beryllium exposures). Environmental exposures to organic bioaerosols should not be overlooked, because hypersensitivity pneumonitis is an important differential to exclude.…”