Sensitization for metals and silica in Dutch sarcoidosis patients
Overig (Sarcoidosis)Clarification of possible etiologic agents in sarcoidosis may lead to a more personal based treatment regime. Although involvement of metals and silica in sarcoidosis pathogenesis is suggested by several case reports and epidemiological studies, it has not systematically been studied in a larger group of sarcoidosis patients. The aim of this study was to characterise both occupational exposure to and sensitization for metals and silica in a well-defined group of sarcoidosis patients and controls. Since sarcoidosis is a very heterogeneous disease, it was investigated whether an occupational history linked to a job exposure matrix (JEM) would be an appropriate method to screen which sarcoidosis patients should be tested for sensitization.
A group of 251 sarcoidosis patients received a questionnaire addressing their complete occupational history. Based on the assumption that there is no relationship between exposure and disease, patients with Obstructive Sleep Apnea Syndrome (OSAS) were included as a control group (n=73). Jobs from sarcoidosis patients and controls were encoded by the International Standard Classification of Occupations 1968 (ISCO68). Encoded jobs were assigned to a JEM to determine metal and/or silica exposure. Consequently, sensitization for metals (aluminium, beryllium and zirconium) and silica was determined in 33 sarcoidosis and 19 control patients, by the use of a lymphocyte proliferation test (LPT).
Although not significant, increased odds ratios were observed for occupational exposure to metals (1.41) and silica (1.81) (Table 1). Furthermore, a significantly higher percentage of sarcoidosis patients (30.3%) showed metal or silica sensitization compared to the control group (5.3%) (fig.1). Of the sarcoidosis patients with metal and/or silica exposure, 23.1% (6/26) showed sensitization for at least one of the tested antigens. Of the unexposed sarcoidosis patients, 57.4% (4/7) had a positive LPT for the antigens tested.
The higher prevalence of sensitization to silica and metals in sarcoidosis patients further supports the hypothesis that metals and silica may be involved in the pathogenesis of a distinct subgroup of sarcoidosis patients. The questionnaire coupled to this JEM seems not an appropriate tool to screen which sarcoidosis patients should be tested for metal and silica sensitization, since almost half of our sensitized patients were classified as unexposed by this method. Finally, the data presented in this study indicates that when searching for causative agents in sarcoidosis patients, besides beryllium, one has to consider sensitization toward zirconium, aluminium and silica in this heterogeneous disease.
Figure 1. Number of sarcoidosis patients and controls with a positive LPT towards the tested antigens. None of the control patients had a positive LPT for silica, zirconium or beryllium. The difference between sarcoidosis patients and controls with a positive LPT towards any of the tested antigens was significant (p=0.04). A LPT was considered positive when the stimulation index was ≥2.5.
Table 1. Estimated odds ratios for sarcoidosis and exposure