RHEUMATOID ARTHRITIS

Rheumatoid arthritis is the most common systemic inflammatory disease characterized by symmetrical joint involvement.
Extraarticular involvement, including rheumatoid nodules, vasculitis, eye inflammation, neurologic dysfunction, cardiopulmonary disease, lymphadenopathy, and splenomegaly, can be manifestations of the disease.

1. RHEUMATOID ARTHRITIS PATHOGENESIS AND THERAPY Dr. S P Srinvas Nayak , Assistant Professor, SUCP Hyderabad

2. RHEUMATOID ARTHRITIS Rheumatoid arthritis is the most common systemic inflammatory disease characterized by symmetrical joint involvement . Extraarticular involvement , including rheumatoid nodules , vasculitis , eye inflammation , neurologic dysfunction , cardiopulmonary disease , lymphadenopathy , and splenomegaly , can be manifestations of the disease . 6/5/2021 2 Dr. S P NAYAK MED EASY LECTURES

3. EPIDEMIOLOGY Rheumatoid arthritis is estimated to have a prevalence of 1% to 2 % It can occur at any age. The disease is three times more common in women . In people ages 15 to 45 years, women predominate by a ratio of 6:1 A majority of patients with rheumatoid arthritis have HLA-DR4, HLADR1 antigens, antigens on T-lymphocytes 6/5/2021 3 Dr. S P NAYAK MED EASY LECTURES

4. AETIOLOGY AND PATHOPHYSIOLOGY The cause of rheumatoid arthritis remains unclear with hormonal , genetic and environmental factors playing a key role. R heumatoid arthritis is characterised by the infiltration of a variety of inflammatory cells into the joint. The synovial membrane, which is normally acellular , becomes highly vascularised and hypertrophied, creating a so-called pannus formation 6/5/2021 4 Dr. S P NAYAK MED EASY LECTURES

5. INFLAMATORY CELLS The inflammatory cells involved in rheumatoid arthritis include T-cells (predominantly CD4 helper cells), B-cells, macrophages and plasma cells . Cytokines are released by these cells which cause the synovium to release proteolytic enzymes, resulting in the destruction of bone and cartilage . Key cytokines involved in rheumatoid arthritis include tumour necrosis factor (TNF)- α, interleukin-1, interleukin- 6 and granulocyte macrophage colony-stimulating factor (GM-CSF). 6/5/2021 5 Dr. S P NAYAK MED EASY LECTURES

6. 6/5/2021 6 Dr. S P NAYAK MED EASY LECTURES

7. 6/5/2021 7 Dr. S P NAYAK MED EASY LECTURES

8. 6/5/2021 8 Dr. S P NAYAK MED EASY LECTURES

9. 6/5/2021 9 Dr. S P NAYAK MED EASY LECTURES

10. 6/5/2021 10 Dr. S P NAYAK MED EASY LECTURES

11. CLINICAL PRESENTATIONS Symptoms ■ Joint pain and stiffness of more than 6 weeks’ duration. May also experience fatigue, weakness, low-grade fever, loss of appetite . Muscle pain and afternoon fatigue may also be present . Joint deformity is generally seen late in the disease. Signs ■ Tenderness with warmth and swelling hands and feet. frequently symmetrical. Rheumatoid nodules may also be present. Laboratory Tests ■ Rheumatoid factor (RF) detectable in 60% to 70%. ■ Anticyclic citrullinated peptide (anti-CCP) antibodies have similar sensitivity to RF (50% to 85%) but are more specific (90 % to 95%) and are present earlier in the disease. ■ Elevated erythrocyte sedimentation rate and C-reactive protein are markers for inflammation. ■ Normocytic normochromic anemia is common as is thrombocytosis . 6/5/2021 11 Dr. S P NAYAK MED EASY LECTURES

12. 6/5/2021 12 Dr. S P NAYAK MED EASY LECTURES

13. EXTRA ARTICULAR INVOLVEMENT Rheumatoid Nodules Vasculitis Pulmonary Complications Ocular Manifestations Cardiac Involvement Felty’s Syndrome 6/5/2021 13 Dr. S P NAYAK MED EASY LECTURES

14. TREATMENT NONPHARMACOLOGIC THERAPY Rest, occupational therapy, physical therapy, use of assistive devices , weight reduction, and surgery are the most useful types of nonpharmacologic therapy used in patients with rheumatoid arthritis. Rest is an essential component of a nonpharmacologic treatment plan . It relieves stress on inflamed joints and prevents further joint destruction . 6/5/2021 14 Dr. S P NAYAK MED EASY LECTURES

15. PHARMACOTHERAPY There are four main categories of drugs employed in the management of rheumatoid arthritis: non-steroidal antiinflammatory drugs (NSAIDs) including cyclo-oxygenase (COX )-2 inhibitors, glucocorticoids , DMARDs and biological therapies. ( DMARD) should be started within the first 3 months of symptom onset. NSAIDs and/or corticosteroids may be used for symptomatic relief if needed 6/5/2021 15 Dr. S P NAYAK MED EASY LECTURES

16. DMARDs All DMARDs inhibit the release or reduce the activity of inflammatory cytokines , such as TNF-α, interleukin-1, interleukin-2 and interleukin-6 . Activated T-lymphocytes have been implicated in the inflammatory process, and these are inhibited by methotrexate , leflunomide and ciclosporin . 6/5/2021 16 Dr. S P NAYAK MED EASY LECTURES

17. Glucocorticoids Glucocorticoids can be given via the oral, intramuscular or intraarticular routes . They act by inhibiting cytokine release and give rapid relief of symptoms and decrease inflammation. Prednisolone is the most commonly used oral steroid. Intra- articular injections, such as triamcinolone or methylprednisolone , are administered into inflamed joints for local anti-inflammatory action, pain relief and to reduce deformity. 6/5/2021 17 Dr. S P NAYAK MED EASY LECTURES

18. 6/5/2021 18 Dr. S P NAYAK MED EASY LECTURES

19. Biologic Agents Biologic agents are genetically engineered protein molecules that block the proinflammatory cytokines TNF- α ( infliximab , etanercept , adalimumab ) and IL-1 ( anakinra ), deplete peripheral B cells ( rituximab ), or bind to CD80/86 on T-cells to prevent the costimulation needed to fully activate T cells ( abatacept ). These drugs may be effective when other DMARDs fail to achieve adequate responses but are considerably more expensive to use. 6/5/2021 19 Dr. S P NAYAK MED EASY LECTURES

20. 6/5/2021 20 Dr. S P NAYAK MED EASY LECTURES

21. Rheumatoid arthritis and pregnancy The management of rheumatoid arthritis during pregnancy is a common challenge, with disease activity improving in approximately 70–80% of patients . Disease activity usually decreases in the first trimester, and this lasts for a number of weeks to months into the postpartum period. Subsequently, 90 % of patients will then experience a flare usually during the first 3 months . None of the available drug treatments for rheumatoid arthritis are absolutely safe in pregnancy . 6/5/2021 21 Dr. S P NAYAK MED EASY LECTURES

22. THANK YOU 6/5/2021 22 Dr. S P NAYAK MED EASY LECTURES