Rheumatoid arthritis (RA) is a chronic autoimmune disease where the immune system mistakenly attacks the body’s own tissues, leading to inflammation and damage primarily within the joints. This persistent inflammation, or synovitis, can destroy cartilage and bone, causing pain, loss of function, and joint deformity. While RA involves genetic and environmental factors, tobacco smoke is consistently identified as the most significant modifiable risk factor associated with both the development and progression of the condition.
How Smoking Increases RA Risk
Cigarette smoking is strongly linked to the initial development of RA, particularly the more aggressive form of the disease that involves autoantibodies. The risk is directly related to the amount and duration of tobacco exposure. Individuals with a low lifetime exposure, such as ten pack-years, face an increased risk of developing the disease by about 26%, and this risk can be more than doubled for heavy, long-term smokers.
This heightened susceptibility is particularly evident in those who are genetically predisposed, specifically individuals who carry the HLA-DRB1 gene. The combination of this genetic marker and smoking creates a synergistic effect, dramatically increasing the likelihood of RA onset compared to either factor alone. The elevated risk can persist for many years after cessation, remaining higher than that of never-smokers even two decades after quitting.
Worsened Disease Severity and Joint Damage
For people already diagnosed with RA, continued smoking accelerates the disease’s destructive course, making it more severe and difficult to control. Smokers typically exhibit higher disease activity scores, which are clinical measures reflecting increased joint swelling, tenderness, and overall systemic inflammation. Inflammatory markers in the blood, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are often elevated in RA patients who continue to smoke.
This inflammatory environment translates to a faster radiological progression, meaning joint erosion and bone damage occur more rapidly. Smoking also increases the risk of extra-articular manifestations, which are complications that affect organs outside the joints. These complications include rheumatoid nodules under the skin, inflammation of blood vessels (vasculitis), and specific types of rheumatoid lung disease.
The Underlying Biological Connection
The mechanism by which smoking drives RA development centers on citrullination, the modification of proteins within the body. Tobacco smoke components increase the expression of the enzyme peptidylarginine deiminase (PAD), particularly in the lung tissue. This enzyme chemically converts the amino acid arginine into citrulline, changing the structure of various native proteins.
The immune system then misidentifies these citrullinated proteins as foreign invaders, triggering an autoimmune response. This reaction leads to the production of anti-citrullinated protein antibodies (ACPA), a characteristic feature and marker of RA. ACPA can be detected in the blood years before the patient experiences any joint symptoms, indicating that the lungs may serve as the initial site where the autoimmune process is triggered. Chronic inflammation and oxidative stress induced by the smoke further perpetuate this cycle.
Reduced Effectiveness of RA Medications
Smoking compromises the efficacy of pharmaceutical treatments used to manage RA, often requiring patients to seek more intensive medication regimens. Studies show that current smokers are less likely to achieve low disease activity or remission compared to non-smoking counterparts when treated with Disease-Modifying Antirheumatic Drugs (DMARDs). For instance, smokers often show an inadequate response to methotrexate, the standard first-line DMARD.
The impact is also notable with biologic drugs, particularly anti-tumor necrosis factor (anti-TNF) agents. Patients who smoke exhibit a reduced clinical response and poorer drug survival rates when taking anti-TNF therapies like infliximab. This reduced effectiveness means the continuous inflammatory input from smoking can override the drug’s intended action, leading to poorer treatment outcomes and a greater need for dose escalation or medication switching.
Improvements Seen After Quitting
Cessation of smoking can reverse many detrimental effects on RA prognosis and treatment response, offering a significant opportunity for better disease management. For individuals who have not yet developed RA, quitting causes the risk of developing the seropositive form to gradually decrease, with a substantial reduction observed after five years and a nearly 40% reduction after 30 years of abstinence.
For those already living with RA, stopping smoking is associated with measurable improvements in disease activity scores and higher rates of achieving clinical remission. Quitting enhances the effectiveness of RA medications, including DMARDs and biologics, resulting in better treatment response rates. Former smokers experience improved functional outcomes and a reduction in systemic inflammation, contributing to a lower overall risk for cardiovascular complications associated with chronic RA.