Rheumatoid Arthritis (RA)

What happens in rheumatoid arthritis

In RA, immune cells and antibodies target the synovium, the thin lining of joints. The synovium thickens and produces inflammatory chemicals that cause swelling and pain. Over time, inflamed tissue (pannus) erodes cartilage and bone, causing deformity. Most joint damage happens in the first years, so early treatment matters most.

RA is a systemic disease: inflammation can also affect other organs and raises the risk of heart disease.

Symptoms

Joint symptoms

• pain, swelling and warmth in several joints
• most often the knuckles and middle finger joints, wrists, and the balls of the feet
• usually symmetrical (both sides)
• morning stiffness lasting more than 30 minutes, sometimes hours
• reduced grip strength and difficulty with buttons, jars and keys
• later: knees, shoulders, elbows, ankles, hips and neck

Whole-body symptoms

• fatigue, often severe
• low-grade fever, weight loss
• feeling generally unwell

Early signs of RA

• swelling of finger joints that makes rings tight
• painful squeeze across the knuckles or the balls of the feet
• stiffness on waking that takes a long time to ease
• tiredness disproportionate to activity

Rheumatoid arthritis vs osteoarthritis

Effects beyond the joints

• Skin: rheumatoid nodules, firm painless lumps under the skin, usually over elbows, fingers or pressure points, and occasionally on the scalp or back of the head; rarely, rheumatoid vasculitis causing skin ulcers, small dark spots around nails or painful sores
• Eyes: dryness (Sjögren's syndrome), scleritis
• Lungs: interstitial lung disease, nodules, pleural effusion
• Heart and blood vessels: higher risk of heart attack and stroke; pericarditis
• Blood: anemia
• Nerves: carpal tunnel syndrome from wrist swelling
• Bones: osteoporosis

Causes and risk factors

• genetics: certain HLA genes (the "shared epitope")
• female sex
• smoking: the strongest modifiable risk factor, especially for anti-CCP-positive RA
• gum disease (periodontitis) and some infections may trigger autoimmunity
• obesity
• family history

Diagnosis

There is no single test. Diagnosis combines:

1. Examination: counting swollen and tender joints.
2. Blood tests: - anti-CCP antibodies: highly specific for RA - rheumatoid factor (RF): positive in many with RA, but also in other conditions and some healthy people - ESR and CRP: measure inflammation - blood count, kidney and liver tests before treatment
3. Imaging: x-rays of hands and feet for erosions; ultrasound or MRI to detect early inflammation.

About 1 in 4 people with RA are seronegative (negative RF and anti-CCP).

Treatment

The goal is remission or low disease activity, using a "treat-to-target" approach with regular reviews and adjustments.

Disease-modifying antirheumatic drugs (DMARDs)

• Methotrexate: the first-choice DMARD, taken weekly with folic acid. Requires regular blood tests. Avoid alcohol excess, and it must be stopped before pregnancy.
• Other conventional DMARDs: hydroxychloroquine, sulfasalazine, leflunomide.

Biologic and targeted medicines

If methotrexate alone does not control RA:

• TNF inhibitors: adalimumab, etanercept, infliximab, certolizumab, golimumab
• other biologics: abatacept, tocilizumab, sarilumab, rituximab
• JAK inhibitors: tofacitinib, baricitinib, upadacitinib (with specific safety cautions)

These increase infection risk, so vaccinations should be up to date and screening for tuberculosis and hepatitis is done first.

Short-term symptom relief

• glucocorticoids (such as prednisone) at low doses for short periods or joint injections during flares
• NSAIDs for pain, following medical advice

Lifestyle and therapy

• regular exercise: aerobic activity, strength training, swimming
• physical and occupational therapy, splints and joint protection
• stopping smoking improves response to treatment
• healthy weight
• heart health: blood pressure, cholesterol and diabetes control
• good sleep and fatigue management
• dental care for gum disease

Surgery

Joint replacement or tendon repair for severe damage.

Outlook

With early, effective treatment, many people with RA achieve remission and prevent joint damage. RA is a lifelong condition with flares and quieter periods. Regular monitoring and attention to heart, lung and bone health are part of long-term care.

Frequently asked questions

What are the first signs of rheumatoid arthritis?

Early signs are painful, swollen joints in the fingers, wrists or feet, often on both sides, with morning stiffness lasting more than 30 minutes and unusual fatigue. Rings may feel tight, and squeezing the knuckles or balls of the feet is painful.

What blood tests diagnose rheumatoid arthritis?

Doctors check anti-CCP antibodies and rheumatoid factor, along with ESR and CRP to measure inflammation. Anti-CCP is the most specific. Some people with RA have negative antibody tests, so diagnosis also relies on examination and imaging.

Can rheumatoid arthritis affect the skin?

Yes. RA can cause rheumatoid nodules, firm lumps under the skin over pressure points such as elbows, fingers and sometimes the back of the head. Rarely, inflamed blood vessels cause ulcers or painful spots. Some RA medicines also cause skin side effects.

What is the best treatment for rheumatoid arthritis?

Methotrexate is usually the first treatment, started as soon as possible after diagnosis. If RA is not controlled, a biologic such as a TNF inhibitor, or a JAK inhibitor, is added. Exercise, therapy and stopping smoking improve results.

Is rheumatoid arthritis hereditary?

Genes increase the risk, and RA can run in families, but most children of people with RA do not develop it. Environmental factors, especially smoking, also play a major role.

Can rheumatoid arthritis go into remission?

Yes. With early and effective treatment, many people reach remission, meaning little or no disease activity. Medicines are usually continued, sometimes at lower doses, to keep RA under control.