Inflammatory Arthritis and Autoimmunity

1. Inflammatory Arthritis and Autoimmunity Sunil Abraham, MD Ellis Rheumatology Associates

2. No disclosures

3. Classification

4. Case presentations

5. Case #1 • 46 year old white female with 4 month history of progressive fatigue associated with worsening joint pains • In the morning her knees are very stiff (1 hour) and her first few steps out of bed are very painful • She has noticed MCP swelling and that her rings are getting tighter • There is numbness and tingling in her fingertips • ROS negative

7. Case #2 • 28 year old male presents with a 5 year history of recurring bilateral ankle pain and swelling. It is associated with extreme morning stiffness. He denies any back pain. He has nail pitting • His brother recently developed a rash on his elbows • MRI of the of right ankle showed significant tendon swelling and subcortical erosions

9. Case # 3 • 82 year white female with history of diabetes, hypertension and coronary disease presents with 2 month history of progressive fatigue, malaise and stiffness in her hips and shoulders • She has never taken an hmg coa reductase inhibitor • Review of systems is negative • Sedimentation rate is normal

10. Case # 4 • An 87 year old white female presents to your office with acute right dorsal wrist swelling, redness, warmth and pain that has been present for 3 weeks • No constitutional symptoms are present • Two courses of antibiotics provide no relief • Xray of her wrist shows chondrocalcinosis of the TFCC; ESR is 90

12. Inflammatory Arthritis • Infiltration of synovial capsule and surrounding joint capsule with lymphocytes, neutrophils, and macrophages • Cardinal signs of inflammation: • Rubor, Calor, Tumor, Dolor • Potential for joint disruption and destruction

13. Acute Inflammatory arthritis • Abrupt onset (hours to days) • Hot, red, swollen, exquisitely tender joint • Constitutional symptoms (fevers, chills, sweats) • Mono-, oligo-, poly- articular

14. Acute Inflammatory arthritis • Differential • Infectious • Bacterial, mycobacterial, fungal • Opportunistic • Lyme (3rd stage) • Crystalline • Monosodium urate- ‘Gout’ • Calcium pyrophosphate- ‘Pseudogout‘

15. Acute Inflammatory arthritis • Rule out mechanical/traumatic injury • Olecranon bursitis, rotator cuff/ achilles tendonitis • Fracture

16. Chronic inflammatory arthritis • Progressive, insidious (>6 weeks) • Morning stiffness > 1 hour • Additional signs of inflammation • Fatigue, malaise, anhedonia • Weight loss, anorexia • ‘Flu like’

17. Chronic inflammatory arthritis • Extra-articular manifestations • Rash (psoriatic, erythema nodosum) • Urethritis or sexually transmitted disease • History of bowel infection (salmonella, shigella) • Inflammatory bowel disease (colitis) • Uveitis • Sicca

18. Connective tissue disease • Disorder with collagen and elastin • Supporting structures • Non-heritable (genetics/environmental) • Rheumatoid arthritis • Systemic lupus erythematosus • Sjogrens Syndrome • Polymyositis, Scleroderma • Heritable • Osteogenesis imperfecta, Marfans, Ehlers-Danlos

19. Connective tissue disease • Review of systems • Signs of inflammation • Arthritis • Patchy alopecia • Oral/nasal ulcerations • Raynauds • Xerophthalmia/ Xerostomia • Rash (distribution, photosensitive) • Proximal muscle weakness

22. Connective tissue diseases • Rheumatoid Arthritis • Systemic Lupus Erythematosus • Sjogrens Syndrome • Systemic Scleroderma • Polymyositis/ Dermatomyositis • Mixed Connective Tissue Disease

23. Labs for Autoimmunity

24. ACR Position Statement • Immunofluorescence testing is the gold standard for ANA testing • HEp-2 cells have multiple autoantigens (>100) • Need to have results reported with titer and pattern • Current technology employs ELISA and multiplex technologies • Allows processing of large volumes • Limits diagnostic accuracy • 8-10 autoantigens

25. Conditions with positive ANA • Essential for diagnosis • SLE • Systemic sclerosis • Mixed connective tissue disease • Somewhat useful • Poly-, Dermatomyositis • Sjogrens • Other conditions with +ANA • Autoimmune hepatitis/thyroid disease • Multiple sclerosis • Malignancy • Age • Infection

26. ANA pearls • Not a screening test • Is there a high pre-test likelihood: • SLE • Scleroderma • Sjogrens • Autoimmune myopathy • Obtain results in titer and pattern • Consider other causes for positivity

27. Related Autoantibodies RA MCTD SLE Sjogrens PM/DM Scl RNP SSA/B Jo-1 dsDNA Smith Scl-70 Centromere RF CCP “ANA-negative”

28. Seronegative Arthritis • Associated conditions: • Psoriatic arthritis • Ankylosing spondylitis • Reactive arthritis • Enteropathic related • Undifferentiated spondyloarthropathy • HLA-B27 • Not useful as a diagnostic test • Presence in 6% of normal population

29. Polymyalgia Rheumatica • ?Autoimmune inflammatory condition • Periarthritis • Subdeltoid bursitis, glenohumeral synovitis, biceps tenosynovitis • Consider diagnosis is those >50 years old, especially >70 • ~15% association with Giant Cell Arteritis • Check ESR, CRP, SPEP • Exquisitely responsive to glucocorticoids • 1-2 years with slow taper

30. Crystalline Arthritis • Monosodium urate deposition (Gout) • Affects 1st MTP, knees, wrist • Destructive • Consider in post menopausal women • Gold standard diagnosis is by joint fluid analysis • Goal uric acid <6 • Calcium pyrophosphate deposition (Pseudogout) • Disruption of cartilage calcification • Senior population

31. Cases Revisited

32. Case #1 • 46 year old white female with 4 month history of progressive fatigue associated with worsening joint pains • In the morning her knees are very stiff (1 hour) and her first few steps out of bed are very painful • She has noticed MCP swelling and that her rings are getting tighter • There is numbness and tingling in her fingertips

33. Case #2 • 28 year old male presents with a 5 year history of recurring bilateral ankle pain and swelling. It is associated with extreme morning stiffness. He denies any back pain. He has nail pitting • His brother recently developed a rash on his elbows • MRI of the of right ankle showed significant tendon swelling and subcortical erosions

34. Case # 3 • 82 year white female with history of diabetes, hypertension and coronary disease presents with 2 month history of progressive fatigue, malaise and stiffness in her hips and shoulders • She has never taken an hmg coa reductase inhibitor • Review of systems is negative. • Sedimentation rate is normal

35. Case # 4 • An 87 year old white female presents to your office with subacute right dorsal wrist swelling, redness, warmth and pain that has been present for 3 weeks • No constitutional symptoms are present • Two courses of antibiotics provide no relief • Xray of her wrist shows chondrocalcinosis of the TFCC; ESR is 90; Uric acid 5.4

36. Conclusions • Appreciate the spectrum of inflammatory arthritis and its relation to connective tissue diseases • Understand the importance of patient demographics in narrowing your differential • Before ordering an ANA, consider whether the patient truly has a connective tissue disease • Always make sure ANA’s are ordered by IFA with titer and pattern • Don’t forget about psoriatic arthritis and pseudogout!