The Industrial Injuries Advisory Council (IIAC) has recently published a report, concerning occupational exposure to crystalline silica and connective tissue diseases, namely systemic sclerosis/scleroderma, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)[i].
Systemic Lupus Erythematosus
SLE is an autoimmune disease which can affect almost all of the body organs and can have many manifestations. It can cause fatigue, flu-like illness, rashes, hair loss, eye problems, mouth ulcers, blood clotting and internal organ problems, such as kidney disease and brain inflammation. Aggressive drug treatment may be taken to control SLE, which affects over 30,000 people in the UK.
Scleroderma is a group of diseases that involve the abnormal growth of connective tissue. It can manifest as hard, tight skin, or, in systemic sclerosis, may affect blood vessels and internal organs. In some cases, the muscles of the oesophagus can lose normal movement and make swallowing difficult. Other symptoms include fatigue, weight loss and swollen painful joints. The association of silica exposure with systemic sclerosis has become known among case reports as ‘Erasmus syndrome’.
RA is an inflammatory disease, caused by the body’s own immune system attacking healthy tissue. The main symptoms are pain, swelling and stiffness in the joints, most commonly in the wrist and finger joints. Other symptoms may affect the whole body, such as fatigue, fever and malaise. The disease may go through phases, or relapse and remission. Alternatively, it can be severe all of the time, causing serious joint damage and disability. The combination of RA and pneumoconiosis (a family of lung diseases that includes silicosis) is well-recognised clinically as ‘Caplan’s syndrome’. Patients can develop silicosis both before and after developing RA.
Background to the 2018 Report
Back in 2005, the Council reviewed a suggested link between exposure to crystalline silica and kidney disease and the 3 connective tissue diseases listed above[ii]. The evidence base was limited then, but some positive associations were still found. The 2018 report therefore functions as an update to the 2005 report.
Relationship Between Connective Tissue Disease Patients and Silica Exposure?
In its report, the IIAC reviewed research published within the last 10 years on a potential causal link.
The Council reviewed studies that investigated an association between each of the connective tissue diseases and silica exposure. Most epidemiological studies adopted 1 of 2 approaches:
- To investigate how the risk of disease varies with silica exposure; or
- To investigate an association between silicosis (which arises out of exposure to silica) and connective tissue disease.
Studies of the 1st type were usually case-control studies, in which patients with connective tissue disease were compared with controls, who did not have the disease. Studies of the 2nd type often involved comparing the prevalence of connective tissue disease among silicosis patients with the prevalence among people who did not have silicosis.
In respect of scleroderma, there were 13 case-control studies, 5 silicosis patient studies and 2 silicosis patient meta-analyses.
In respect of SLE, there were 5 case-control studies and 3 silicosis patient studies.
Researchers found a large cohort study of more than 240,900 Swedish construction workers, who were hospitalized between 1997 and 2010. They estimated the participants’ exposure to silica and recorded diagnoses of connective tissue diseases, including sclerosis and SLE. A 39% increase in risk of connective tissue disease, as a consequence of silica exposure, was recorded.
In respect of RA, there were 11 studies in silica-exposed workers, 1 review, 1 meta-analysis of silica-exposed workers, and 5 silicosis patient studies.
Other studies into patient antibodies and studies of animals support the plausibility of a causal relationship between exposure to silica and connective tissue disease. Though some biological actions of silica in the body are understood, the mechanism by which silica exposure may induce such diseases in humans has not been firmly established. There are a priori reasons to suspect that silica could promote autoimmune disease.
Quality of the Evidential Basis for Association
The Council found that the evidence base for an association between occupational silica exposure and connective tissue disease is deeper than it was 10 years ago. Collectively, the studies provide reasonable evidence in support of causation. In some reports, the risks of scleroderma and systemic sclerosis are doubled with silica exposure, but other reports claim that the risk is less than doubled. There is less supportive evidence for an association of SLE and RA with silica, although some studies have found a more than doubling of risk among workers with silica exposure.
In many studies, silica exposure is classed as ‘high’, ‘probable’, or given a subjectively calculated score, all of which are unsuitable measures for addition to the IIDB scheme. There was little evidence for an increase in risk in any particular occupation.
As an alternative to prescription based on job title, the Council considered the case for prescription in workers with silicosis. Estimates of increased risk of connective tissue diseases among silicosis patients were significant, often more than doubled. However, a clinical link between silicosis and connective tissue disease may have influenced diagnosis rates in some studies. Moreover, in studies which selected participants from hospital settings, silicosis patients would likely have suffered multiple serious diseases upon hospitalisation. As such, silicosis could have been falsely associated with connective tissue disease when an alternative condition was the genuine cause.
Collectively, the new studies provide reasonable evidence in support of an occupational hazard; the evidence is stronger for systemic sclerosis/scleroderma than the other 2 conditions. However, addition to the list of prescribed diseases for Industrial Injuries Disablement Benefit was not possible because of difficulty specifying the type of occupational exposure that the claimant would need to have experienced. The Council also considered prescribing the disease specifically in workers who have silicosis but was unable to justify this because studies on this topic were of insufficient quality. Thus, occupational exposure to crystalline silica and the 3 aforementioned tissue disorders was not recommended for addition to the list of prescribed diseases at this time.
The IIAC drew several conclusions from its report:
- Taking this body of evidence overall, there is clear evidence of a hazard; crystalline silica is likely to be a cause of connective tissue disease in some circumstances.
- It is not feasible to define a suitable exposure schedule based on actual exposures or job title(s).
- Marked associations have been found between silicosis and connective tissue diseases, although the number of reports is small and limitations of the study methods limit the scope for prescription in the silica-exposed workforce.
- Acquiring sufficient evidence on doubling of risks for diseases that are rare is challenging.
[i] Occupational Exposure to crystalline silica and its relation to connective tissue diseases. Industrial Injuries Advisory Council. Position paper 42. June 2018 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/717051/occupational-exposure-to-crystalline-silica-and-its-relation-to-connective-tissue-diseases-iiac-position-paper-42.pdf (Accessed 12 July 2018)
[ii] Silica-related renal and connective tissue diseases: IIAC position paper 14. 10 November 2005 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/328599/iiac-pp14.pdf (Accessed 12 July 2018)