Rheumatoid Arthritis.pptx

Presentation

1. RHEUMATOID ARTHRITIS BY SIMWANZA W

2. Intro The musculoskeletal system is responsible for: movement of the body , provides a structural framework to protect internal organs , acts as a reservoir for storage of calcium and phosphate in the regulation of mineral homeostasis .

3. Bones Bones fall into two main types based on their embryonic development . Flat bones , such as the skull, develop by intramembranous ossification, in which embryonic fibroblasts differentiate directly into bone within condensations of mesenchymal tissue during early fetal life. Long bones , such as the femur and radius, develop by endochondral ossification from a cartilage template.

4. .. The normal skeleton has two forms of bone tissue; Cortical bone , formed from Haversian systems is dense and forms a hard envelope around the long bones Trabecular or cancellous bone , fills the centre of the bone and consists of an interconnecting meshwork of trabeculae , separated by spaces filled with bone marrow.

5. Main cell types in bone Osteoclasts: multinucleated cells of haematopoietic origin , responsible for bone resorption . Osteoblasts : mononuclear cells of mesenchymal origin , responsible for bone formation . Osteocytes : these differentiate from osteoblasts during bone formation and become embedded in bone matrix.

6. Joints Bones are linked by joints. There are three main subtypes : fibrous , fibrocartilaginous synovial

7. Types of joints Type Range of movement Examples Fibrous Minimal Skull sutures Fibrocartilaginous Limited Symphysis pubis Costochondral junctions Intervertebral discs Sacroiliac joints Synovial Large Most limb joints Costal vertebral Temporal-mandibular

8. RHEUMATOID ARTHRITIS

9. Intro.. Rheumatoid arthritis (RA) is the most common persistent inflammatory arthritis, occurring throughout the world and in all ethnic groups . The prevalence is lowest in black Africans and Chinese, and highest in Pima Indians. It is an auto immune condition.

10. .. The clinical course is prolonged, with intermittent exacerbations and remissions . Patients with RA have an increased mortality when compared with age-matched controls, primarily due to an increased risk of cardiovascular disease . This is most marked in those with severe disease, with a reduction in expected lifespan by 8–15 years. Around 40 % of RA patients are registered as disabled within 3 years of onset, and around 80% are moderately to severely disabled within 20 years.

11. Pathophysiology Genetic, epigenetic and environmental factors are implicated in the pathogenesis of RA . It has long been thought that RA may be triggered by an infectious agent in a genetically susceptible host, but a specific pathogen has not been identified . Periodontal disease and oral pathogens have been implicated, as have gastrointestinal organisms , and viruses such as Epstein–Barr and cytomegalovirus .

12. .. Cigarette smoking is a strong risk factor for developing RA, especially in people with HLA-DR4 , and is also associated with greater disease severity and reduced responsiveness to DMARD and biological treatment. Susceptibility is increased postpartum and by breastfeeding, indicating that hormone/immune interactions may be important.

13. .. The clinical onset of RA is characterised by infiltration of the synovial membrane with lymphocytes, plasma cells , dendritic cells and macrophages. CD4 + T lymphocytes, including Th1 cells and Th17 cells play a central role by interacting with other cells in the synovium . Lymphoid follicles form within the synovial membrane in which T cell–B cell interactions lead B cells to produce cytokines and autoantibodies, including RF and ACPA.

14. .. Synovial macrophages are activated by immune complexes and local damage-associated molecules acting to produce proinflammatory cytokines, including TNF, IL-1, IL-6 and IL-15. These act on synovial fibroblasts, to promote swelling of the synovial membrane and damage to soft tissues and cartilage.

15. .. The RA joint is hypoxic and this promotes new blood vessel formation( neoangiogenesis ). Thus the inflamed synovium becomes vascularised , with highly activated endothelial cells supporting the recruitment of yet more leucocytes to perpetuate the inflammatory process. Amongst the range of inflammatory mediators present in the RA joint, TNF plays an important role by regulating production of other cytokines.

16. Clinical features The typical presentation is with; joint pain joint swelling stiffness affecting the small joints of the hands, feet and wrists Large joint involvement, systemic symptoms and extra-articular features may also occur.

17. O/E T ypical features of symmetrical swelling of the MCP and PIP joints. Joints are tender on pressure when actively inflamed and have stress pain on passive movement . Erythema is unusual and its presence suggests coexistent sepsis.

18. Deformities- Hand S wan neck’ deformity T he boutonnière or ‘button hole’ deformity The Z deformity of the thumb Dorsal subluxation of the ulna at the distal radio-ulnar joint

19. Butonnaire deformity

20. Swan neck deformity

21. Combination of hand deformities

22. Deformities- Foot/leg D orsal subluxation of the MTP joints may result in ‘cock-up ’ or hammer toe deformities. In the hindfoot , calcaneovalgus ( eversion).This is often associated with loss of the longitudinal arch (flat foot) due to rupture of the tibialis posterior tendon . Popliteal (‘Baker’s’) cysts may occur

23. Feet deformities

24. Extra articular manifestations Systemic Fever and weight loss Fatigue Susceptibility to infection Musculoskeletal Muscle-wasting Tenosynovitis Osteoporosis Haematological Anaemia Thrombocytosis Eosinophilia

25. Cont … Cardiac Pericarditis, Myocarditis and Endocarditis Conduction defects Pulmonary Pleural effusions Fibrosing alveolitis Bronchiolitis Neurological Cervical cord compression Compression neuropathies Peripheral neuropathy

26. .. Lymphatic Felty’s syndrome Splenomegaly Nodules Sinuses Fistulae Ocular Episcleritis and Scleritis Vasculitis Digital arteritis Ulcers Pyoderma gangrenosum

27. Investigations The diagnosis of RA is based on clinical grounds but investigations are useful in confirming the diagnosis and assessing disease activity The ESR and CRP are usually raised but normal results do not exclude the diagnosis . ACPA are positive in about 70% of cases and are highly specific for RA, occurring in many patients before clinical onset of the disease . RF is positive in about 70% of cases, many of whom also test positive for ACPA. Ultrasound examination and MRI are not routinely required in patients with obvious clinical signs Plain X-rays of the hands , wrist and feet are of limited value in early RA but certain changes are characteristic, including periarticular osteoporosis and marginal joint erosions.

28. European league against Rheumatism/American college of Rheumatology diagnostic criteria Criterion Score Joints affected 1 large joint 0 2–10 large joints 1 1–3 small joints 2 4–10 small joints 5 Serology Negative RF and ACPA 0 Low positive RF or ACPA 2 High positive RF or ACPA 3

29. Cont.. Duration of symptoms Score <6 wks >6 wks 1 Acute phase reactants Normal CRP and ESR 0 Abnormal CRP or ESR 1 Patients with a score>=6 are considered to have definite RA

30. Treatment The mainstay of treatment in RA comprises the early use of small-molecule disease-modifying antirheumatic drugs (DMARDs), and corticosteroids for induction of remission. Early use of DMARD therapy improves clinical outcome in RA. Partial or nonresponse to DMARD therapy should prompt escalation of the dose or use of an additional DMARD, with progression to biological drugs if necessary

31. .. Regular monitoring of DMARD therapy is essential because of the risk of liver and haematological toxicity . Some DMARDs are contraindicated in pregnancy especially during the first trimester Patients who wish to become pregnant should be counselled to stop DMARD treatment while they try to conceive.

32. DMARDs Methotrexate is the anchor DMARD in RA . Sulfasalazine (SSZ) is widely used, both alone and in combination with methotrexate and other drugs . Hydroxycholoroquine is given usually in combination with other DMARDs . Leflunomide can be used alone or in combination with other drugs.

33. Corticosteroids Systemic corticosteroids have disease-modifying activity, but their primary role is in the induction of remission in patients with early RA who are starting synthetic DMARD treatment. Intramuscular steroids are often used to treat flares of disease activity in patients who are established on DMARD therapy. In the context of RA, osteoporosis is probably the most important SE since this is a known complication of RA

34. Biologics The use of biological agents (often abbreviated to ‘biologics ’)is reserved for the treatment of patients who have high disease activity despite having had an adequate trial of traditional DMARDs . These agents are targeted towards specific cytokines and other cell surface molecules regulating the immune response . B iological treatment is more effective than standard DMARD therapy, treatment but costs are significantly greater and increase chances of infection since they suppress the immunity

35. examples Rituximab Abatacept Anakinra Tocilizunab

36. Other treatment measures Surgery General measures; Physical rest , analgesics and NSAID may be required to control symptoms. Passive exercises and joint protection measures In the vast majority, management is outpatient but hospital admission can be helpful in patients with very active disease for a period of bed rest, multiple joint injections , splinting, regular hydrotherapy, physiotherapy and education.

37. Prognosis Factors that associate with a poorer prognosis are ; disability at presentation, female gender, involvement of MTP joints, radiographic damage at presentation, smoking positive RF or ACPA.

38. Ahsanteni sana