Inflammatory Arthritis and Autoimmunity Sunil Abraham, MD Ellis Rheumatology Associates

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Classification Arthritis Inflammatory Infectious Septic Osteomyelitis Crystalline Monosodium urate Calcium pyrophosphate Autoimmune Rheumatoid Seronegative (HLA-B27) ANA related Vasculitis, Sarcoid, Misc Polymyalgia rheumatica Non-Inflammatory Osteoarthrosis

Case presentations

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

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

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

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

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

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

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

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

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

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

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

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

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

Labs for Autoimmunity

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

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

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

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

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

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

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

Cases Revisited

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

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

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

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

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!