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

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Abstract

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.

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About the authors

Igor L. Serdyuk

Russian Medical Academy of Continuous Professional Education; Kazan (Volga Region) Federal University

Email: dr.serdyuc@mail.ru
ORCID iD: 0000-0002-9890-3755
SPIN-code: 4067-5062

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education; laboratory assistant, Central research laboratory, Assistant Professor, Depart. of Internal Medicine, Institute of Fundamental Medicine and Biology

Russian Federation, 11 Mushtary street, 420012 Kazan; Kazan

Anna R. Valeeva

Russian Medical Academy of Continuous Professional Education; Kazan (Volga Region) Federal University

Email: anna-valeeva@mail.ru
ORCID iD: 0000-0001-5218-9341
SPIN-code: 4922-7323

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education; Cand. Sci. (Medicine), Senior Researcher, Central research laboratory, Senior lecturer, Depart. of Applied Ecology, Institute of Ecology, Biotechnology and Nature Management

Russian Federation, 11 Mushtary street, 420012 Kazan; Kazan

Marina O. Korovina

Russian Medical Academy of Continuous Professional Education; Kazan (Volga Region) Federal University

Email: koporulina.mo@gmail.com
ORCID iD: 0000-0002-2307-928X
SPIN-code: 1756-6530

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education; Researcher, Central research laboratory, Postgraduate student, Depart. of Biochemistry, Biotechnology and Pharmacology Institute of Fundamental Medicine and Biology

Russian Federation, 11 Mushtary street, 420012 Kazan; Kazan

Yves Renaudineau

Universite Toulouse III — Paul Sabatier

Email: renaudineau.y@chu-toulouse.fr
ORCID iD: 0000-0001-5098-5002

Dr. Sci. (Pharmacy), Professor, Depart. of Immunology

France, Toulouse

Marina I. Arleevskaya

Russian Medical Academy of Continuous Professional Education; Kazan (Volga Region) Federal University

Author for correspondence.
Email: marleev@mail.ru
ORCID iD: 0000-0002-0584-446X
SPIN-code: 2513-6093

Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education; Cand. Sci. (Medicine), Senior Researcher, Central research laboratory, Associate Professor, Depart. of Internal Medicine, Institute of Fundamental Medicine and Biology

Russian Federation, 11 Mushtary street, 420012 Kazan; Kazan

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2. Fig. 1. Differences in the severity of some external and individual indicators in patients with eRA, provoked by various triggers: a — the severity of situational anxiety; b — the severity of personal anxiety; c — the average duration of one infectious episode; d — the annual total duration of all infectious episodes; e — the number of infectious episodes in the year preceding the examination; f — BMI. Differences were assessed using the Mann–Whitney test for independent samples. eRA — patients with early rheumatoid arthritis, meeting the diagnostic criteria of the disease ACR/EULAR2010 with a disease duration of less than a year. BMI — Body Mass Index.

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3. Fig. 2. Differences in the severity of some external and individual indicators in the persons with preclinic joint symptoms provoked various triggers: a — the severity of situational anxiety; b — personal anxiety; c — the average duration of one infectious episode; d — the annual total duration of all infectious episodes; e — the number of infectious episodes in the year preceding the examination; f — BMI. Differences were assessed using the Mann–Whitney test for independent samples. Pre-RA — individuals with preclinical joint symptoms, not meeting the diagnostic criteria of the disease ACR/EULAR2010. BMI — Body Mass Index.

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4. Fig. 3. Clinical and laboratory differences in cases of preclinical joint symptoms provoked by different triggers. a — ESR; b — Score of arthralgia signs; c — HAQ. Differences were assessed using the Mann–Whitney test for independent samples. Pre-RA — individuals with preclinical joint symptoms, not meeting the diagnostic criteria of the disease ACR/EULAR2010. ESR — Erythrocyte sedimentation rate. Arthralgia score — total number of arthralgia signs according to EULAR recommendations. HAQ — severity of functional insufficiency of joints according to the HAQ questionnaire, points.

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