Rheumatoid Arthritis: Understanding Causes, Diagnosis, and Treatment Options

Rheumatoid arthritis (RA) is a long-term autoimmune condition that mainly affects the joints. The body’s immune system, which normally protects us from infections, mistakenly attacks the lining of the joints (synovium). This leads to pain, swelling, stiffness, and, if untreated, joint damage. RA can also affect other parts of the body such as the eyes, lungs, and heart.

9/22/20252 min read

Rheumatoid arthritis (RA) is a long-term autoimmune condition that mainly affects the joints. The body’s immune system, which normally protects us from infections, mistakenly attacks the lining of the joints (synovium). This leads to pain, swelling, stiffness, and, if untreated, joint damage. RA can also affect other parts of the body such as the eyes, lungs, and heart.

Pathogenesis (How RA Develops)

RA is caused by a combination of genes, environment, and immune system changes.

  • Genes: Certain genetic markers, like HLA-DRB1, increase the risk.

  • Triggers: Smoking, infections, or gut microbiome changes may start the immune reaction in those at risk.

  • Immune response: The body produces autoantibodies (like rheumatoid factor and anti-CCP). Immune cells release inflammatory substances (TNF-α, IL-1, IL-6), which cause swelling, pain, and damage to cartilage and bone.

Diagnosis

  • Detecting RA early is important because damage often starts within the first two years.

  • Symptoms: Joint pain and swelling (usually in both hands, wrists, or feet), morning stiffness lasting more than 30 minutes, fatigue, and mild fever.

Blood tests:

  • Rheumatoid Factor (RF): common but not specific.

  • Anti-CCP (ACPA): highly specific for RA.

  • ESR and CRP: show ongoing inflammation.

  • Imaging: X-rays, ultrasound, or MRI can show joint inflammation and early damage.

  • Clinical criteria: Doctors use the ACR/EULAR 2010 guidelines, which combine symptoms, blood tests, and imaging findings.

Treatment

Treatment aims to control inflammation, reduce pain, and prevent joint damage.

Lifestyle & supportive care:

  • Stay active with low-impact exercises (swimming, yoga, walking).

  • Quit smoking and maintain a healthy weight.

  • Physical and occupational therapy can help with mobility and daily activities.

Medications:

  • NSAIDs (e.g., ibuprofen): reduce pain and stiffness but don’t slow the disease.

  • Steroids (e.g., prednisone): short-term relief during flares.

  • DMARDs (disease-modifying antirheumatic drugs):

  • Methotrexate is the most commonly prescribed.

  • Others include hydroxychloroquine, leflunomide, and sulfasalazine.

  • Biologics: advanced treatments that block specific immune pathways (e.g., TNF inhibitors like adalimumab, IL-6 inhibitors like tocilizumab, or rituximab for B cells).

  • JAK inhibitors: newer oral drugs like tofacitinib.

  • Surgery: For severe joint damage, options include joint replacement or synovectomy.

References

  1. Pathogenesis & Overview - Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016 Oct 22;388(10055):2023–2038. doi:10.1016/S0140-6736(16)30173-8.

  2. Classification & Diagnosis - Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569–2581. doi:10.1002/art.27584.

  3. Treatment Guidelines

    • Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685–699. doi:10.1136/annrheumdis-2019-216655.

    • Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2021 Jul;73(7):1108–1123. doi:10.1002/art.41752.

  4. Role of Imaging in RA - Colebatch AN, Edwards CJ, Østergaard M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013 Jun;72(6):804–814. doi:10.1136/annrheumdis-2012-203158.

  5. Biologic & Targeted Therapies - Smolen JS, Genovese MC, Takeuchi T, et al. Safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis (SELECT-COMPARE): a randomized, double-blind, double-dummy, phase 3 trial. Lancet. 2019 Nov 23;394(10208):1849–1858. doi:10.1016/S0140-6736(19)32491-6.