Triggering role of environmental and individual factors in rheumatoid arthritis and preclinical joint symptoms

BACKGROUND: Rheumatoid arthritis (RA) is a phenotypically heterogeneous disease. AIM: The study aimed to identify the role of triggers in the onset of RA and preclinical joint symptoms, as well as their association with clinical and laboratory parameters. METHODS: Data on potential disease triggers and preclinical joint symptoms were collected from patients with early RA (n = 461) and their relatives (n = 247). Moreover, 299 healthy participants (control group) were examined for past infections within the previous 6–12 months. Anxiety levels, number of childbirths, age at onset of menopause, and body mass index (BMI) were assessed. Additionally, the association of triggers with composite disease activity indices, morning stiffness duration, severity of functional joint impairment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF) was assessed. Data were analyzed using the Mann–Whitney test, multiple regression analysis, and Spearman correlation. RESULTS: The most common triggers for RA and preclinical joint symptoms were menopause (17.6%, 11.7%), infections (13.4%, 15.8%), and psychological stress (15.2%, 18.2%). Preclinical joint symptoms were additionally provoked by physical exertion (19.8%). RA triggered by infections or menopause was associated with an increased frequency and duration of infections (p 0.001) and higher BMI (p = 0.019 and p = 0.024, respectively) compared with controls. A similar association was observed between preclinical joint symptoms triggered by infections and increased frequency and duration of infections (p 0.001). Additionally, joint symptoms triggered by physical exertion were associated with more frequent and prolonged infections compared with the control group (p = 0.015 and p = 0.016, respectively). ESR levels exhibited a heightened response when preclinical joint symptoms were associated with infections (p = 0.010), menopause (p = 0.033), or physical exertion (p = 0.020) in comparison with their response to psychological stress. The arthralgia score was highest when provoked by menopause compared with cases provoked by infection (p = 0.053) or childbirth (p = 0.012). Preclinical joint symptoms triggered by psychological stress were associated with a higher arthralgia score than those provoked by physical exertion (p = 0.002). In the preclinical group, ESR and CRP levels correlated with BMI (p = 0.005 and p = 0.028, respectively). In patients with RA, ACPA (p = 0.044) and RF (p = 0.009) concentrations were associated with personal anxiety levels. CONCLUSION: The influence of triggers on clinical and laboratory parameters is evident in preclinical RA. The highest arthralgia scores were observed in cases triggered by menopause or psychological stress. Joint symptoms associated with infections, menopause, or physical exertion were associated with higher ESR levels.