What Is Rheumatoid Arthritis? | NEJM

Summary

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease affecting millions globally, with women at higher risk. It leads to joint damage, particularly in hands and feet, causing pain, stiffness, and systemic complications. Though genetic factors and environmental triggers like smoking contribute to its onset, the exact cause remains unclear. Early diagnosis and treatment are critical for preventing irreversible damage. RA treatment has advanced significantly in recent decades, with options like DMARDs, biologics, and targeted therapies. While current treatments are effective, ongoing research into personalized therapy and prevention holds promise for better management of the disease.

Takeaways

• 😀 Rheumatoid arthritis (RA) is an autoimmune disease that affects millions globally, causing joint inflammation and impacting various organs and systems.
• 😀 RA typically presents with symmetrical polyarthritis of the hands and feet, and morning stiffness lasting more than 30 minutes is a common sign.
• 😀 Women are 2-3 times more likely than men to develop RA, and the disease typically affects individuals between the ages of 30 and 70.
• 😀 Genetic factors, such as certain HLA-DR alleles, and environmental factors, particularly smoking, contribute to the development of RA.
• 😀 Early diagnosis and treatment are crucial for improving the quality of life and preventing irreversible joint damage in RA patients.
• 😀 RA is classified as seropositive (with autoantibodies like rheumatoid factor and ACPA) or seronegative, with seropositive RA typically being more severe.
• 😀 The preclinical stage of RA can last from 4 to 10 years, with autoantibodies developing before the onset of symptoms.
• 😀 Environmental triggers, including viral infections and smoking, can cause changes in immune function, contributing to RA development.
• 😀 Targeted therapies, including biologics and Janus kinase inhibitors, have revolutionized RA treatment by addressing specific immune pathways.
• 😀 Treatment is individualized based on the patient's disease mechanisms, as some may respond better to specific treatments like anti-TNF or anti-IL-6.
• 😀 Although significant progress has been made in RA treatment, lifelong management is necessary, and efforts are underway to prevent or delay the onset of the disease.

Q & A

What is rheumatoid arthritis (RA) and how does it affect the body?

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that primarily affects the joints, especially the hands and feet. It causes symmetrical polyarthritis, inflammation, and can also affect other organs and systems in the body, leading to joint destruction and systemic issues.

What is the significance of morning stiffness in RA diagnosis?

Morning stiffness lasting longer than 30 minutes is a common clinical sign of rheumatoid arthritis, distinguishing it from other forms of inflammatory arthritis. This prolonged stiffness is often an indicator of the disease.

How do genetic and environmental factors contribute to the development of RA?

Genetic factors, such as specific HLA-DR alleles, increase the likelihood of developing RA, while environmental factors like smoking can trigger the disease. These factors contribute to immune system dysfunction, leading to RA's onset.

How is rheumatoid arthritis diagnosed?

RA is diagnosed clinically by examining the number and location of affected joints, disease durationRA Q&A Development (6 weeks or more), acute phase reactants, and potentially an X-ray for bone erosions. Laboratory tests for autoantibodies, such as rheumatoid factor and anti-citrullinated protein antibodies, help differentiate between seropositive and seronegative RA.

What is the difference between seropositive and seronegative RA?

Seropositive RA is characterized by the presence of autoantibodies like rheumatoid factor and anti-citrullinated protein antibodies, while seronegative RA lacks these markers. Seropositive RA is typically associated with more severe disease and greater joint damage.

What happens during the preclinical phase of RA?

The preclinical phase of RA can last up to 10 years, during which patients may produce autoantibodies like rheumatoid factor or anti-CCP antibodies without showing full symptoms. This phase is characterized by immune system changes, and environmental triggers like viral infections or smoking can eventually activate the disease.

What role does citrullRA Diagnosis and Insightsination play in RA development?

Citrullination is a process where the amino acid arginine is converted to citrulline, which is recognized as foreign by the immune system in predisposed individuals. This triggers an immune response, leading to the production of autoantibodies, contributing to the onset of RA.

What are the main therapeutic approaches for RA treatment?

RA treatment involves Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including conventional DMARDs like methotrexate, biologic DMARDs, and targeted synthetic DMARDs like Janus kinase inhibitors (JAK inhibitors). The goal is to control inflammation, prevent joint destruction, and improve quality of life.

How does methotrexate work in treating RA?

Methotrexate, a conventional DMARD, works by upregulating adenosine, an anti-inflammatory molecule, suppressing multiple pro-inflammatory immune pathways. It reduces the production of cytokines and decreases inflammation in RA patients.

What is the 'treat to target' concept in RA management?

The 'treat to target' concept involves setting specific treatment goals for controlling inflammation. Using disease activity scores, clinicians aim to reduce inflammation as much as possible, striving for remission or low disease activity in patients with RA.