Could the significantly increased risk of rheumatoid arthritis reported in Italian male steel workers be explained by occupational exposure to cadmium?

Murphy, Daniel; James, Benjamin; Hutchinson, David

doi:10.1186/s12995-016-0111-z

Cited by 14 publications

(6 citation statements)

References 7 publications

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“…It could be hypothesized that eating fish may reduce the risk of inflammatory diseases because it is a major source of long-chain polyunsaturated fatty acids (PUFAs), especially n-3 PUFAs and micronutrients that may have anti-inflammatory properties and may modulate immune responses [9–11]. Gestational exposure to n-3 PUFAs is well known to have beneficial effects on children’s subsequent health [12] On the other hand, fish is contaminated by marine pollutants, mainly PCBs, dioxins and other polychlorinated compounds, and heavy metals [13, 14]. The positive effect of these PUFAs may therefore in part counterbalance the toxic impact of contaminants.…”

Section: Discussionmentioning

confidence: 99%

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Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study

2019

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Background The etiology of Juvenile Idiopathic Arthritis (JIA) is poorly understood. The purpose of this study was to examine the possible influence of early nutrition on later development of JIA. Methods In a population-based prospective birth cohort of 15,740 children we collected nutritional data, including fish consumption, and biological samples during pregnancy, at birth and at different ages. 16 years after study inclusion we identified 42 children with JIA, of whom 11 were positive for Antinuclear Antibodies (ANA). Heavy metals were analysed in cord blood of all 42 JIA patients and 40 age and sex-matched controls. A multivariable logistic regression model, adjusted for relevant factors, was used as well as Mann-Whitney U-test. Results Fish consumption more than once a week during pregnancy as well as during the child’s first year of life was associated with an increased risk of JIA (aOR 4.5 (1.95–10.4); p < 0.001 and aOR 5.1 (2.1–12.4) p < 0.001) and of ANA-positivity (aOR 2.2 (1.4–3.6); p = 0.002 and p < 0.001). Concentrations of Al, Cd, Hg and Li in cord blood were significantly higher in the JIA-group than in controls. The ANA-positive, all of whom had consumed fish >once/week their first year, had significantly higher concentrations of Al ( p < 0.001), Cd ( p = 0.003), and Li ( p < 0.001) in cord blood than controls. Frequency of fish consumption correlated with concentrations of Cd ( p = 0.003), Li ( p = 0.015) and Hg ( p = 0.011). Conclusions Moderate exposure to heavy metals, associated with fish consumption, during pregnancy and early childhood may cause effects on the immune system of the offspring, resulting in ANA positivity and JIA.

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Section: Discussionmentioning

confidence: 99%

“…Murphy et al have suggested that cadmium inhalation could be a plausible trigger for RA [13]. Smoking is highly associated with RA [12, 14].…”

Section: Discussionmentioning

confidence: 99%

Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study

2019

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“…Given that the process is induced in vivo by cadmium and that cadmium levels are higher in smokers [ 93 , 94 ] the association of cadmium inhalation from smoking with nodule formation in the lungs of RA patients is the strongest evidence yet for a causative involvement of metal ions in the disease [ 11 ]. In addition to smoking, epidemiological evidence for the association between cadmium inhalation and nodular rheumatoid arthritis stems from occupational settings such as workers in the mining, steel, textile, and other industries [ 95 , 96 , 97 ]. It is thought that the inhaled cadmium leads to nodules (granulomas) in the lung and the observed formation of RF, ACPAs and other autoantibodies that are typical of RA.…”

Section: Zinc and Cadmium In The Aetiology And As Risk Factors Of mentioning

confidence: 99%

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Frangos

Maret

2020

Nutrients

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Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment.

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“…A retrospective cohort study of workers recycling scrap metals at an electrical arc furnace in Italy noted 3/331 incident cases of RA over a 20 year follow up period, a dramatically increased RR of 6.18 (95%CI 2.00-19.02), when compared to 420/20332 incident RA cases in the same town over the same period [ 33 ]. Despite the relatively small sample size and lack of directly comparable working group, this cohort demonstrated an appreciably elevated RA risk, thought due to foundry dust exposure containing a range of potential toxins including heavy metals [ 34 ].…”

Section: Inhalational Workplace Exposuresmentioning

confidence: 99%

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

Hutchinson

2017

TORJ

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Background:Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3–1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development.Objective:The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a “double-hit” phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production.Method:A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption.Conclusion:We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology.

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Could the significantly increased risk of rheumatoid arthritis reported in Italian male steel workers be explained by occupational exposure to cadmium?

Cited by 14 publications

References 7 publications

Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study

Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

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