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To determine the association of allergic conditions with incident rheumatoid arthritis (RA), especially in relation to smoking history and anti-citrullinated peptide antibody (ACPA) status.This case-control study included 3515 incident RA cases and 5429 matched controls from the Epidemiological Investigation of Rheumatoid Arthritis study 1995 to 2016, including questionnaire-based information on eight allergic conditions composed from a list of 59 unique allergies. We used logistic regression and adjusted ORs (aOR) to assess the association between allergic conditions and risk of RA, adjusting for age, sex, residential area, body mass index, education, and smoking, and stratified by smoking and ACPA.A history of any reported allergy was equally common in RA (n=1047, 30%) as among population controls (n=1540, 29%), aOR 1.04, 95% CI 0.95 to 1.15. Metal, respiratory, food, plant/pollen and chemical allergies were not associated with risk of RA. By contrast, statistically significant associations were observed for animal dander allergy (6% vs 5%, aOR 1.37, 95% CI 1.03 to 1.82), especially in ACPA-positive RA (aOR 1.46 95% CI 1.06 to 2.01) and for atopic dermatitis, in particular for older and ACPA-negative RA (aOR 2.33, 95% CI 1.37 to 3.96 at age 80). Never smokers with allergic rhinitis also had increased risk of developing RA (aOR 1.30, 95% CI 1.00 to 1.68).Most common allergies do not increase risk of RA, nor do they protect against RA. However, some allergic conditions, notably animal dander allergy, atopic dermatitis and allergic rhinitis, were associated with an increased risk for RA.

ObjectiveMost studies of rheumatoid arthritis (RA) and sleep have focused on established RA. We here investigate sleep quality and sleep duration in patients with newly diagnosed RA and during 1–12 years after diagnosis.MethodsData were collected on sleep 1–12 years after diagnosis from patients diagnosed 1998–2018 in the Swedish study Epidemiological Investigation of RA. Six sleep domains (sleep problems, non-restorative sleep, insomnia, insufficient sleep, sleep quality perceived as poor and sleep considered a health problem); a global sleep score and time spent in bed were estimated. Using logistic regression, ORs were calculated for each sleep outcome by disease duration. We explored whether pain (low (Visual Analogue Scale=0–20 mm, reference), intermediate=21–70, high=71–100) or functional impairment (Health Assessment Questionnaire>1.0) was associated with problems.ResultsWe had sleep data on 4131 observations (n=3265 individuals). Problems with ≥1 sleep domain (global sleep score) was reported in 1578 observations (38%) and increased with disease duration (OR 1.04, 95% CI 1.02 to 1.07). Median time in bed was 8 hours (Q1-Q3: 7.5–9.0). High-grade pain increased the likelihood of sleep problems ~3–9 fold, and increased functional impairment ~4–8 fold.ConclusionIn this cohort of newly diagnosed patients with RA with access to the current treatment from diagnosis, we did not find any major problems with sleep, and existing sleep problems related mainly to pain and reduced function. Treatment of sleep problems in RA should be guided towards treating the underlying problem causing the sleep disturbance.

Background Environmental factors play a prominent role in rheumatoid arthritis (RA) aetiology. Shift work has previously been associated with increased RA risk in females. The aim of this study was to investigate the potential association, including a dose-response association, between permanent night shift work, rotating shift work and day-oriented shift work and risk of developing anticitrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA. Methods The present report is based on a population-based, case-control study with incident cases of RA (1951 cases and 2225 controls matched by age, gender and residential area). Using logistic regression, occurrence of RA among subjects who have been exposed to different kinds of shift work was compared with that among those who have never been exposed by calculating the OR with a 95% CI. Results Rotating shift work and day-oriented shift work increased the risk of developing ACPA-positive RA (OR 1.3, 95% CI 1.0 to 1.7 and OR 1.3, 95% CI 1.0 to 1.6), but not ACPA-negative RA. Permanent night shift work appeared to be a protective factor both against ACPA-positive RA (OR 0.7, 95% CI 0.6 to 0.9) and ACPA-negative RA (OR 0.8, 95% CI 0.6 to 1.0). For both subsets of RA, significant trends showed a lower risk of developing RA with increasing duration of permanent night shift work (p value for trend 0.002 vs 0.04). Conclusions Sleep restriction as a consequence of shift work is associated with several biological effects among which changes in melatonin production may be involved. The present epidemiological findings of a complex relationship between sleep patterns and different forms of RA may be of importance for increasing the understanding of the pathophysiology of RA.

ObjectiveAirborne agents including cigarette smoke associate with an increased risk of rheumatoid arthritis (RA). We analysed to which extent occupational exposure to asbestos and silica confers an increased risk of developing serologically defined subsets of RA.MethodsThis Swedish population-based case-control study enrolled incident RA cases between 1996 and 2013 (n=11 285), identified through national public authority and quality registers, as well as from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Study. Controls (n=1 15 249) were randomly selected from Sweden’s population register and matched on sex, age, index year and county. Occupational histories were obtained from national censuses. Exposure to asbestos and silica was assessed by job-exposure matrices. Logistic regression was used to calculate ORs adjusted for age, sex, county, index year, alcohol use and smoking.ResultsResults showed that male workers exposed to asbestos had higher risk of seropositive RA (OR=1.2, 95% CI 1.0 to 1.4) and seronegative RA (OR=1.2, 95% CI 1.0 to 1.5) compared with unexposed workers. The risk was highest among workers exposed to asbestos from 1970, before a national ban was introduced. Male workers exposed to silica also had higher risk of RA (seropositive RA: OR=1.4, 95% CI 1.2 to 1.6; seronegative RA: OR=1.3, 95% CI 1.0 to 1.5). For the largest subset, seropositive RA, the OR increased with the number of years exposed to silica, up to OR=2.3 (95% CI 1.4 to 3.8, p for trend ConclusionsIn conclusion, we observed an association between asbestos exposure and risk of developing RA and extended previous findings of an association between silica exposure and RA risk, where a dose-response relationship was observed.

ObjectivesThe relationship between alcohol consumption and risk for rheumatoid arthritis (RA) is incompletely understood. We aimed to determine the influence of alcohol on anticitrullinated protein antibody (ACPA) positive and ACPA-negative RA and investigate potential interactions between alcohol consumption, smoking and the presence of human leucocyte antigen (HLA)-DRB1-shared epitope (SE).MethodsA Swedish population-based case–control study with incident cases of RA was used (3353 cases, 2836 matched controls). Subjects with different HLA-DRB1-SE status, smoking and alcohol consumption were compared regarding risk of ACPA-positive and ACPA-negative RA, by calculating OR with 95% CI employing logistic regression. Interaction on the additive scale between alcohol, HLA-DRB1-SE and smoking was estimated by calculating the attributable proportion (AP) due to interaction.ResultsCompared with non-drinking, low and moderate alcohol consumption was dose dependently associated with a reduced risk of ACPA-positive and ACPA-negative RA. Independent of smoking habits, non-drinking and the presence of HLA-DRB1-SE interacted to increase the risk of ACPA-positive RA. Among HLA-DRB1-SE positive subjects, there was also a significant interaction between non-drinking and smoking with regard to risk for ACPA-positive RA. A three-way interaction was observed between alcohol, smoking and HLA-DRB1-SE with regard to risk for ACPA-positive RA (AP 0.7, 95% CI 0.6 to 0.8) that remained significant when the influence from the two-way interactions was removed (AP 0.4, 95% CI 0.2 to 0.6).ConclusionsOur findings emphasize the need to investigate complex interactions between several environmental and genetic factors in order to better understand the etiology of RA. Whereas of great interest in an aetiological perspective, the finding of a protective role of alcohol on risk for RA must, however, be interpreted with caution in a clinical and public health perspective.

Objectives To investigate (1) whether working in cold environment (WCE) is associated with an increased risk of developing rheumatoid arthritis (RA) (overall), anticitrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA and (2) whether WCE interacts with occupational physical workload in conferring RA risk. Methods Data from the Swedish population-based case-control study Epidemiological Investigation of Rheumatoid Arthritis involving 3659 incident cases and 5925 controls were analysed. Study participants were asked whether they had ever worked in cold/outdoor environment along with their exposure duration and frequency. Occurrence of RA among exposed and unexposed subjects were compared by calculating ORs with 95% CI using logistic regression. Additive interactions between WCE and six types of physical workload were assessed using the principle of departure from additivity by calculating attributable proportion due to interaction (AP). Results The OR associated with having ever worked in cold environment was 1.5 (95% CI 1.4 to 1.7) for RA (overall), 1.6 (95% CI 1.4 to 1.8) for ACPA-positive RA and 1.4 (95% CI 1.2 to 1.6) for ACPA-negative RA. The risk of developing RA increased with increasing cumulative dose of working in cold indoor environment (p value

Objectives This study investigated: (1) the association of physical workload (PW) and risk of rheumatoid arthritis (RA); (2) the potential interactions between PW and the genes in the human leucocyte antigen (HLA) region. Methods A population-based case–control study involving incident cases of RA (3150 cases and 5130 controls) was performed using data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis. Information on 7 types of self-reported PW exposure and HLA-DRB1 genotypes of cases and controls were gathered. Anticitrullinated protein antibody (ACPA) status of cases was identified. For each PW exposures, exposed participants were compared with unexposed participants. ORs with 95% CIs of RA (overall), ACPA-positive RA and ACPA-negative RA associated with different PWs were estimated using logistic regression. HLA-PW interactions were estimated using the principle of departure from additivity of effects by calculating attributable proportion (AP) due to interaction. Results ORs of developing RA associated with 6 various PW exposures ranging from 1.3 (95% CI 1.1 to 1.4) to 1.8 (95% CI 1.6 to 2.0) were observed. Exposure to more types of PW was associated with increasing risk for RA (p