Osteoarthritis, Rheumatoid Arthritis, and Spondylarthropathies

1. Osteoarthritis, Rheumatoid Arthritis, and Spondylarthropathies Timothy Niewold, MD Assistant Professor Section of Rheumatology

2. Question: A 45 yo woman with history of rheumatoid arthritis presents to the emergency room with a 2 day history of a severely painful, warm, swollen R knee. Her other joints are not painful, and until recently her symptoms were well controlled on methotrexate and prednisone. The most appropriate next step in management is: A. obtain an X-ray of the knee B. increase prednisone C. increase methotrexate D. aspirate the knee E. prescribe physical therapy

3. Question: A 54 yo man presents with symmetric pain and swelling of the small joints in his hands and wrists progressive over the last 3 months. He has no fever, weight loss, or constitutional symptoms. Laboratory testing shows high ESR, negative rheumatoid factor, and a positive anti-CCP antibody test. The next step in management is: A. Prescribe methotrexate B. Check an anti-nuclear antibody test C. Prescribe a tumor-necrosis factor alpha blocker D. Prescribe a non-steroidal anti-inflammatory drug and follow up in 6 months E. Order an MRI of the hand and wrist

4. Question: A 59 year old woman is seen in clinic for a 4 year history of gradually worsening bilateral hand pain. She has not noted redness, swelling, or morning stiffness. You suspect osteoarthritis clinically, and would expect to see all of the following on hand X-ray except: A. Joint space narrowing in the DIP joints B. Sclerosis near the articular surface C. Bony erosions D. Heberden’s and Bouchard’s nodes E. Hypertrophic changes

5. Question: A 23 yo man presents with a 4 year history of progressive low back pain. He says the pain is worst in the morning, gradually improving with activity. X-rays were done and he was told they were normal at the start of his symptoms four years ago. Narcotic pain did not relieve his pain. He thinks his symptoms may have started around the time of a car accident. He is seeing you in second opinion for his chronic back pain. What should be done next? A. X-ray of the L-spine and pelvis B. Referral to PT C. MRI of the L-spine D. Arrange X-ray guided steroid injection E. Increase narcotic dose

6. Osteoarthritis – definition and prevalence Definition – degenerative joint process characterized by focal loss of cartilage, new bone formation (spurring), and subsequent pain and loss of function Most common type of arthritis – more than half of individuals over age 55 have radiographic evidence, goes up to 90% at age 70 Slight female predominance in older age, but both sexes affected

7. Uncertain pathogenesis but: Genetic factors play a role Clear environmental or secondary triggers injury history of inflammatory joint condition, neuropathic (Charcot joint) rare endocrine/metabolic such as hemochromatosis, acromegaly, Wilson’s disease Osteoarthritis – pathogenesis

8. History is important – gradual onset of symptoms, lack of inflammation, sometimes history of prior injury or overuse or other secondary trigger Physical exam – crepitance, hypertrophic changes, lack of erythema or warmth, usually not much tenderness X-ray will confirm diagnosis – asymmetric joint space narrowing, sclerosis near the joint line, and spurring are characteristic Osteoarthritis – diagnosis

9. X-ray – classic changes due to OA

10. Very common Associated with obesity Bilateral disease is common although one may be worse Treatment – NSAIDs or Tylenol, PT and weight loss, then steroid injections for knee and potentially X-ray guided for hip, and if these fail total joint replacement surgery is very effective Osteoarthritis – Hip and Knee

11. Heberden’s nodes – DIP joint bony nodules Bouchard’s nodes – PIP joint bony nodules Both “nodes” are diagnostic for hand OA, 10 times more common in women than men, and have a strong genetic component Base of thumb (1st CMC joint) very commonly affected, more likely due to wear-and-tear than nodes Treatment – NSAIDs or Tylenol, can do injections particularly for base of thumb, rarely ever surgery Osteoarthritis – Hands

12. Shoulder uncommon in 40s and 50s, but becomes very common in 7th and 8th decades of life Rotator cuff symptoms often accompany Treatment – NSAIDs, infrequent injections. Total replacement is possible, but used rarely because not as successful as hip + knee Feet 1st MTP commonly affected (“bunion” deformity) Treatment – better shoes, surgery for severe Osteoarthritis – Shoulder and Feet

13. Joints which are not typically affected by OA unless injury/secondary cause: MCPs Wrist Ankle Elbow If these are affected, think inflammatory!! Osteoarthritis –Joints Not Typically Affected

14. Rheumatoid Arthritis – definition and prevalence Definition – symmetric inflammatory joint condition characterized by pannus formation, joint erosion, and systemic inflammation Most common inflammatory arthritis, 1% of the population, 2:1 female to male ratio, peak incidence between ages 40 to 60 Onset usually insidious over months

15. Genetic factors clearly important – HLA “shared epitope” is strongest risk factor, but also non-HLA genes such as PTPN22, STAT4, TNFAIP3 Environmental factors – cigarette smoking increases both risk of disease and severity of disease, also risk in coal miners (Kaplan syndrome) Rheumatoid Arthritis – Predisposition

16. Longitudinal Course of RA CCP, cyclic citrullinated peptide; CTLA4, cytotoxic T-lymphocyte antigen 4; GP39, cartilage glycoprotein 39; PADI4, peptidyl arginine deiminase, type IV; PTPN22, protein tyrosine phosphatase, non-receptor type 22. Reproduced with permission from McInnes IB, et al. Nat Rev Immunol. 2007;7(6):429-442. 16

17. History and physical are majority of diagnosis – lab not that helpful Symmetric pain and swelling in small joints of hands, wrists, feet, ankles most common, followed by knees, elbows, shoulders Morning stiffness – better with activity Constitutional symptoms – fatigue, even weight loss are common, but fever is VERY RARE Steady, progressive, additive onset is by far most common presentation Rheumatoid Arthritis – Diagnosis

18. Patterns of Onset Insidious 55%-65% Joint stiffness, swelling, pain, fatigue Acute 8%-15% Fever, weight loss, fatigue, joint abnormalities present but often not prominent Intermediate 15%-20% Systemic complaints more noticeable than insidious onset Harris ED Jr, et al. In: Firestein GS, et al, eds. Kelley’s Textbook of Rheumatology, 8th ed. 2008.

19. Joints Commonly Involved

20. Rheumatoid Arthritis – Extra-articular features Rheumatoid nodules Pleural effusions Atherosclerosis (new, but probably testable) Scleritis Rheumatoid vasculitis (rare) Felty’s syndrome (neutropenia, splenomegaly, recurrent infection)

21. High ESR or CRP common but not required Rheumatoid factor positive in about 50% RF usually indicates more severe disease, greater likelihood of extra-articular manifestations Anti-CCP antibodies - relatively new (but very clinically useful and testable!!) Found in about 50% of patients without much overlap with rheumatoid factor Highly sensitive – positive test almost always indicates disease (>90% specificity for RA, even in mixed autoimmune cohorts) So can “rule in”, but low sensitivity prevents “rule out” Rheumatoid Arthritis – Laboratory

22. Major RA Subsets Based on ACPA Reproduced with permission from Klareskog L, Catrina AI, Paget S. Lancet. 2009;373(9664):659-672. 22

23. Classical findings of inflammatory arthritis: Periarticular joint erosions Periarticular osteopenia Symmetric joint space narrowing Note that each of these is the opposite of OA!! (erosions instead of spurs, osteopenia instead of sclerosis, and symmetric instead of asymmetric joint narrowing) Rheumatoid Arthritis – X-ray

24. Early Radiographic Progression Joint-space narrowing and erosion are seen in up to two thirds of patients within the first 2 to 5 years of disease Reproduced with permission from Wolfe F, et al. Arthritis Rheum. 1998;41(9):1571-1582.

25. Rheumatoid arthritis erosions on X-ray

26. Early RA: Radiographic Findings High-Detail X-Ray Low-Field MRI Courtesy of Charles Peterfy, MD.

27. Early treatment with a disease modifying drug is standard of care Non-disease modifying NSAIDs Prednisone Disease modifying Methotrexate – most common first line, usually around 15-20mg/week with daily folate 1mg/day Sulfasalazine, leflunomide also effective Biological agents such as TNF-alpha blockers, abatacept, rituximab, and tocilizumab are all second or third line Rheumatoid Arthritis – Treatment

28. Goal of treatment is clinical remission if possible Control of disease prevents bone erosions and subsequent deformity and loss of function All disease modifying drugs are immunosuppressive, non-biologics have risk of GI intolerance and hair loss, TNF blockers are associated with re-activation of tuberculosis and rarely an MS-like disease, other biologics are not currently in wide use Rheumatoid Arthritis – Treatment

29. Spondylarthropathies – Definition and Prevalence Group of inflammatory conditions affecting the axial skeletion (spine, pelvis), may also demonstrate asymmetric oligoarthritis and enthesitis (inflammation of tendon insertions) Prevalence – about 1 per 1000 in US, ankylosing spondylitis characterized by a 3:1 male to female ratio

30. Spondylarthropathies – Patterns of Disease • Inflammatory spinal involvement is typical, and differentiates from other arthridities • Enthesitis or inflammation of tendon insertions is classical • Asymmetric oligoarthritis is typical pattern of peripheral joint arthritis • Eye involvement (uveitis) is common • Aortitis with valvular insufficiency is also an important complication

31. Spondylarthropathies Ankylosing Spondylitis Psoriatic Arthritis Enteropathic Arthritis and Reactive Arthritis

32. Spondylarthropathies - Ankylosing Spondylitis Sacroileitis in all cases, ascending ankylosis of spine gradually over the years Symptoms are inflammatory back pain Can also affect hips and shoulders, rare to affect more distal joints HLA-B27 in 90% of European ancestry Diagnosis – Sacroileitis and anklyosis on X-ray Treatment – NSAIDs for mild disease, sulfasalazine or methotrexate, TNF-blockers are effective second-line therapy

33. X-ray of sacroileitis

34. Ankylosing spondylitis: lumbar vertebrae, bamboo spine

35. Spondylarthropathies - Psoriatic Arthritis A subset of patients with psoriasis (5-7%) have psoriatic arthritis Inflammatory spine disease and peripheral oligoarthritis common, can affect DIP joints Diagnosis – Psoriasis required, X-rays often show erosive joint disease with little osteopenia, destructive changes such as “pencil-in-cup” Treatment – Steroids may result in flare of skin disease when tapered, methotrexate and sulfasalazine common, TNF-blockers as second line therapy

36. Psoriatic arthritis: hand

37. Spondylarthropathies - Enteropathic Arthritis and Reactive Arthritis Enteropathic arthritis – spondylarthritis associated with inflammatory bowel disease, spine + peripheral joints, rx. for IBD works for arthritis, too Reactive arthritis – spondylarthropathy following GI or GU infection. Often self-limited, but can either be recurrent or persistent

38. Questions???