1. Rheumatoid Arthritis Dr ahad azami

2. Rheumatoid Arthritis Systemic Systemic Chronic Chronic Inflammatory Inflammatory Primarily targets the synovium of diarthrodial joints Primarily targets the synovium of diarthrodial joints Etiology likely combination genetic and environmental Etiology likely combination genetic and environmental

3. Diarthrodial Joint

4. Rheumatoid Arthritis Female: male 3:1 Female: male 3:1 4 th -6 th decades of life 4 th -6 th decades of life Symmetric polyarthritis Symmetric polyarthritis Extra-articular manifestations Extra-articular manifestations Subcutaneous nodules/lung nodules Subcutaneous nodules/lung nodules Scleritis Scleritis Vasculitis Vasculitis Felty’s syndrome Felty’s syndrome

7. Stages of RA Pathogenesis StageSymptomsFindings 1.AntigenNoneNone PresentationNormal X-ray to T Cells to T Cells 2.T and B CellMalaise, Mild,Swelling or Pain Proliferation,Joint Stiffnessof Small Joints AngiogenesisSwellingWrists, Knees in SynoviumNormal, X-ray ACR

8. Stages of RA Pathogenesis (Continued) StageSymptomsFindings 3.SFPMNJoint Pain,Warm, Swollen AccumulationSwellingJoints, Inc SF Synovial CellAM Stiffness,Soft Tissue ProliferationMalaise,Proliferation, WeaknessLimited ROM, Nodules, Soft Tissue Swelling on X-ray ACR

9. Stages of RA Pathogenesis (continued) Stage Symptoms Findings 4.Pannus Same as Same as Invasion, Stage 3Stage 3 ChondrocytePeriarticular Activation,Osteopenia, Enzyme Proliferative ActivationPannus on MRI ACR

10. Stages of RA Pathogenesis (continued) Stage SymptomsFindings 5.Subchondral Same asSame as stage 3 Bone Erosion, Stage 3Plus Instability Pannus Plus LossFlexion Invasion of of FunctionContractures, Cartilage DeformityExtra-Articular StretchedDisease, Early LigamentsErosions and Joint Space Narrowing on X-Ray ACR

11. Synovium in RA

12. PIP Swelling

13. Ulnar Deviation, MCP Swelling, Left Wrist Swelling

15. Joints involved in RA

16. Don’t forget the cervical spine!! Instability there can lead to impingement of the spinal cord Don’t forget the cervical spine!! Instability there can lead to impingement of the spinal cord Thoracolumbar, sacroiliac, and distal interphalangeal joints of the hand are not involved Thoracolumbar, sacroiliac, and distal interphalangeal joints of the hand are not involved

17. Extra-articular Symptoms Patients that are more likely to get are: Patients that are more likely to get are: RF+ RF+ HLA DR4+ HLA DR4+ Male Male

18. Corneal Melt

19. Nodules

20. Pulmonary Nodules

21. Felty’s Syndrome Seropositive Rheumatoid Arthritis Seropositive Rheumatoid Arthritis Splenomegaly Splenomegaly Granulocytopenia Granulocytopenia ACR

22. Large Granular Lymphocytes

23. Labs Can also see nonspecific abnormalities Can also see nonspecific abnormalities High sedimentation rate High sedimentation rate Anemia Anemia Hypergammaglobulinemia Hypergammaglobulinemia Thrombocytosis Thrombocytosis

24. Rheumatoid Factor Antibodies that recognize Fc portion of IgG Antibodies that recognize Fc portion of IgG Can be IgM, IgG, IgA, IgE Can be IgM, IgG, IgA, IgE 85% of patients with RA over the first 2 years become RF+ 85% of patients with RA over the first 2 years become RF+

26. Anti-ccp

28. Radiographic Features Peri-articular osteoporosis Peri-articular osteoporosis Uniform joint space narrowing Uniform joint space narrowing Marginal erosions Marginal erosions Soft tissue swelling Soft tissue swelling Subluxations Subluxations Symmetric Symmetric Cysts Cysts

33. Synovial Fluid Inflammatory Inflammatory WBCs 5000-50,000 WBCs 5000-50,000 ≥ 50% neutrophils ≥ 50% neutrophils No crystals No crystals Negative Cultures Negative Cultures

34. Noninflammatory on left Inflammatory on right

35. ACR Criteria Morning Stiffness ≥1 hour Morning Stiffness ≥1 hour Soft tissue swelling of ≥ 3 joints observed by physician Soft tissue swelling of ≥ 3 joints observed by physician Swelling of proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints Swelling of proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints These signs and symptoms must be present ≥ 6 weeks These signs and symptoms must be present ≥ 6 weeks

36. ACR Criteria Continued Symmetric Arthritis present for ≥ 6 weeks Symmetric Arthritis present for ≥ 6 weeks Subcutaneous nodules Subcutaneous nodules Positive Rheumatoid Factor Positive Rheumatoid Factor Radiographic Erosions or periarticular osteopenia in hand or wrist joints Radiographic Erosions or periarticular osteopenia in hand or wrist joints Must have ≥4 criteria to meet diagnosis of RA

39. Criteria for Progression of RA Stage I – Early Stage I – Early No Destructive Changes Osteoporosis on X-Ray Stage II – Moderate Stage II – Moderate Osteoporosis and Slight Subchondral Bone or Cartilage Destruction Cartilage Destruction No Joint Deformaties, Mobility May be Limited Adjacent Muscle Atrophy Adjacent Muscle Atrophy Nodules or Tenosynovitis May be Present ACR

40. Criteria for Progression of RA (continued) Stage III – Severe Stage III – Severe Osteoporosis and Erosions Deformity Without Ankylosis Extensive Muscle Atrophy Nodules and Tenosynovitis Stage IV – Terminal Stage IV – Terminal Fibrous or Bony Ankylosis Features of Stage III ACR

41. Management Focused on relieving pain and preventing damage/disability Focused on relieving pain and preventing damage/disability Patient education about the disease is key Patient education about the disease is key Physical Therapy for stretching and range of motion exercises Physical Therapy for stretching and range of motion exercises Occupational Therapy for splints and adaptive devices Occupational Therapy for splints and adaptive devices Surgery Surgery

42. Rheumatoid Arthritis: Classification of Function Class I: No Limitations Class II: Adequate for Normal Activities Despite Joint Discomfort of Limitation of Movement Class III: Inadequate for Most Self-Care and Occupational Activities Occupational Activities Class IV: Largely or Wholly Unable to Manage Self- Care; Restricted to Bed or Chair ACR

44. Medicines Non-Steroidal anti-inflammatories (NSAIDS) for symptom control Non-Steroidal anti-inflammatories (NSAIDS) for symptom control Prednisone for quick control of joint inflammation but cannot use long term due to side effects Prednisone for quick control of joint inflammation but cannot use long term due to side effects Osteoporosis, cataracts, weight gain, insulin resistance, dyslipidemias Osteoporosis, cataracts, weight gain, insulin resistance, dyslipidemias

45. Disease Modifying Anti- rheumatic Agents Drugs that actually control the disease and not just treat symptoms Drugs that actually control the disease and not just treat symptoms Should be used early on in patients Should be used early on in patients Erosions can develop in the joints of patients within the first two years of disease Erosions can develop in the joints of patients within the first two years of disease

46. Disease Modifying Anti- rheumatic Agents Hydroxychloroquine-for mild disease, takes a long time to reach steady state, very benign in side effect profile Hydroxychloroquine-for mild disease, takes a long time to reach steady state, very benign in side effect profile Sulfasalazine-for mild disease, toxicities include GI upset Sulfasalazine-for mild disease, toxicities include GI upset Azathioprine-for moderate disease, not as modifying as other drugs, cytopenias Azathioprine-for moderate disease, not as modifying as other drugs, cytopenias

47. Disease Modifying Anti- rheumatic Agents Methotrexate-moderate to severe disease, very successful in preventing erosions, liver toxicities Methotrexate-moderate to severe disease, very successful in preventing erosions, liver toxicities Anti-TNFα agents-used for mod-severe disease, but moving up as first line drug, TB reactivation a concern Anti-TNFα agents-used for mod-severe disease, but moving up as first line drug, TB reactivation a concern

48. Prognosis RA can shorten the life span 3-18 years RA can shorten the life span 3-18 years Most die from cardiovascular disease, infection or lymphoproliferative disorders Most die from cardiovascular disease, infection or lymphoproliferative disorders Overall RA patients are much better off than at any other time in history due to ongoing research and new meds!! Overall RA patients are much better off than at any other time in history due to ongoing research and new meds!!