Rheumatology Basics

1. Rheumatology Basics Kalyani McCullough, MD Clinics and MOP Didactic

2. Purpose of this talk • To provide a foundation for: • Seeing patients in Rheumatology clinic • Getting started on the work-up of suspected rheumatologic diseases in your clinic • Review most common rheumatologic diseases • Fast overview • Resource for later

3. Main diseases you’ll be seeing • Inflammatory arthritis • Rheumatoid, spondyloarthropathies • Crystal arthritis • Gout, Pseudogout • Autoimmune disorders • Lupus, Sclerodema, Autoimmune myositis • Vasculitis • Large, medium, small vessel

4. What are some clues your patient may have a rheumatologic disease? • Constitutional symptoms • Fevers, sweats, weight loss, fatigue • Subacute time course • Started over weeks to months • Characteristic symptoms • Mono or polyarticular joint pain, multisystem complaints (i.e. skin, lung, GI) • Are there signs of an inflammatory process? • Synovitis, rash, serositis, elevated ESR/CRP

5. How do you get started on the work-up? • Thorough physical exam • Lab tests • CBC w diff, ESR, CRP, ANA, targeted autoantibodies • Radiographs • Erosive arthritis, sacroillitis • Biopsy? • Skin, muscle, kidney

6. Basics of treatment • NSAIDs • Symptom relief, especially joint pain • Glucocorticoids • Acutely, try to use steroid sparing agent if possible • Disease-modifying antirheumatic drugs (DMARDs) • Synthetic DMARDs • Slow onset, 2-6 months • Methotrexate, Hydroxychloroquine, Sulfasalazine, Azathioprine, Mycophenolate mofetil, Cyclophosphamide • Biologic DMARDs • Bioengineered protein drugs (antibodies or receptor-antibody chimeras ) • IV or SQ only • Rapid onset • Screen for and treat LTBI, HBV first • Infliximab, Etancercept, Rituximab

7. Steroid Side Effects • Weight gain • Diabetes • Cataracts • Insomnia • Fluid retention • Hypertension • Proximal weakness • Alopecia • Sweats • Osteoporosis • Infection • Psychiatric disturbance (eg, depression, mania, psychosis) • Easy bruising of the skin • Stress • Tremor • Peptic ulcer disease

8. Long term considerations for most autoimmune diseases • Increased risk of CV death due to inflammation and accelerated atherosclerosis • Aggressive risk factor reduction: BP<120/80, LDL<100 • Osteoporosis from glucocorticoids • Dexa screening, Calcium-Vit D, bisphosphonates prn • Infections • Increased risk of certain malignancies • Lymphoma, Lung/Cervical CA in Lupus

9. Inflammatory Arthritis • Rheumatoid arthritis • Spondyloarthropathies • Axial skeletal involvement and polyarthritis of peripheral joints • Ankylosing spondylitis • Reactive arthritis • Psoriatic arthritis • IBD-associated arthritis

10. Rheumatoid arthritis • Clinical presentation: • Chronic, symmetric polyarthritis • Often starts with the PIPs, MCPs, MTPs • Can affect most synovial joints (wrists, knees, elbows etc.) • Doesn’t affect DIPs • Morning stiffness, pain, swelling (vs. OA: worse with activity) • Labs: • RF, anti-CCP Ab or both in 70% of patients • RF not specific, anti-CCP 90-98% specific • ACD, ESR, CRP • Xrays: • articular erosions and joint space narrowing

11. Joint distribution in RA vs. OA

12. RA – Physical Exam Findings • Ulnar deviation • at mcps • Swan neck deformity • hyperextension of PIPs, flexion of DIPs • Boutonniere deformity • flexion of PIP, hyperextension of DIP

13. OA – Physical Exam Findings Bony outgrowths/ calcific spurs on PIPs and DIPs

14. RA – Extra-articular Manifestations • Many extra-articular findings: • Rheumatoid nodules • Other organ involvement: • Sjogren’s syndrome • Scleritis • Interstitial fibrosis • Pericardial effusions • Peripheral neuropathy • Amyloidosis

15. RA - Treatment • Early aggressive treatment leads to better longterm outcomes • Glucocorticoids acutely • MTX frequently used • Start 7.5mg weekly, increase to a max dose of 20-25mg weekly • Give with folate 1mg daily to reduce toxicity • Check CBC, AST/ALT, Cr q 3 mo • Contraindications: liver disease, HBV/HCV, alcohol use, CrCl<30 • Toxicities: oral ulcers, nausea, hepatotoxicity, BMS, pneumonitis

16. Sponydloarthropathies • Inflammatory arthritis with involvement of: • Sacroiliac (SI) joint • Axial spine • Tendon fascia • Ligament insertion points (entheses) • Peripheral joints

17. Spondyloarthropathies • Ankylosing Spondylitis • Psoriatic Arthritis • DIPs often involved, assoc with nail pitting • Reactive Arthritis • Triggered by GI/GU infection • IBD-associated arthritis • Correlates with bowel activity

18. Ankylosing Spondylitis • Clinical presentation • Inflammatory back pain in young adult • Reduction in spinal mobility, particularly lumbar flexion • Association with anterior uveitis • Labs • Increased relative risk of HLA-B27 • Xray • - Sacroiliitis • Treatment • - PT, NSAIDs

19. Crystal Arthritis Gout – Natural History 1) Asymptomatic hyperuricemia • Over production or under excretion (or both) 2) Acute and intermittent gout • Attacks triggered by fluctuations in UA level (up or down) and deposition of UA crystals in joint • Acute monoarthritis, often 1st attack is at 1st mtp • After years see bony erosions on xray 3) Chronic tophaceous gout

20. Gout - Treatment • Acute attack – most efficacious if initiate treatment within 48h of onset • NSAIDs – indomethacin • Avoid if h/o PUD or renal impairment • Colchisine • 1.2mg PO x 1, then 0.6mg 1h later and q24h until symptoms improve • Side effects: Diarrhea, abdominal pain, NSAIDs better tolerated • Reduce dose if Cr > 1.5, risk of neuromuscular toxicity • Glucocorticoids • Prednisone 20-40mg/d, taper 1-2 wks after symptoms resolve

21. Gout - Prophylaxis • Goal UA<6 • Xanthine oxidase inhibitors (decrease production) • Allopurinol • Start with 100mg daily, gradually increase dose • Max is 800mg/d, though 300-400mg usually effective • Reduce dose if diminished Cr • Hypersensitivity reaction can be fatal, more common in older patients with impaired Cr on diuretics • If develop rash, stop • Febuxostat • Metabolized by liver, so better with renal impairment • Ok with mild-moderate hepatic insufficiency • Uricosuric agents (increase excretion) • Probenacid • Age <65, good renal function, not on more than ASA 81 daily • Side effects: rash and GI symptoms

22. Pseudogout • Clinical presentation • Intermittent monoarthritis, often knee/wrist, though can be 1st mtp • Labs • rhomboid shaped, positively birefringent calcium pyrophosphate dihydrate (CPPD) crystals • Can be associated with other diseases: hemochromatosis, thyroid disease • Treatment • NSAIDs, colchisine

23. Autoimmune disorders • Systemic lupus erythematosis (SLE) • Antiphospholipid antibody syndrome • Raynaud’s phenomenon • Scleroderma • Sjogren’s Disease • Dermatomyositis and Polymyositis • Relapsing Polychondritis

24. Lupus • Clinical presentation • Typically affects women of childbearing age • Multisystem relapsing/remitting disease • Affects skin, musculoskeletal, renal, CV, pulmonary, GI, CNS, psych • - Hallmark symptoms: photosensitive rash, polyarthritis, serositis, fatigue • - Renal and CNS involvement -> significant morbidity

25. Lupus • Labs • Presence of antinuclear antibodies • Once ANA positive, no need to recheck • Anti-dsDNA and anti-Sm have great specificity, but lack sensitivity. • Hypocomplementemia may occur during flares. • C3, C4, CH50 • Treatment • Glucocorticoids, DMARDs

26. Lupus - Monitoring • Lupus nephritis – approx 50% • Typically immune complex glomerulonephritis • Screen q3 mo: • Ask about polyuria, nocturia, foamy urine • Look for HTN and edema • Labs: UA – RBC casts, spot prot: Cr ratio • Diagnose with biopsy • Increased risk of malignancy: Hodkin’s and Non-Hodgkins lymphoma, Lung CA, Cervical CA • Annual cervical CA screening

27. Scleroderma • Clinical presentation • Early in disease: • msk pain, fatigue, weight loss, GERD • Rare disorder, but symptoms common in primary care • Late in disease: • Skin: thickening, ischemic digital ulcers, pitting, telangectasias on face and palms • Lungs: interstitial fibrosis, pulmonary htn • GI: GERD, dysphagia • Renal: rare, but Scleroderma Renal Crisis (SRC) is life threatening emergency • Cardiac: ischemic injury • MSK: erosive arthritis, tendon friction rub • CREST (limited scleroderma): calcinosis, raynaud’s, esophageal dysmotility, sclerodactyly, telangectasias

28. Scleroderma Thickened, tight skin Digital ulcers Sclerodactyly Telangectasias

29. Scleroderma • Labs • If negative ANA, diagnosis is very unlikely • Indirect immunofluorescence better than ELISA • Anti-centromere Ab in 20-40% • Anti-Scl-70 (anti-topoisomerase) 20-40% • Correlates with worse prognosis • Treatment • No proven disease-modifying medication • Screening and early identification of internal organ involvement important • Organ specific treatment • Fibrosis – immunosuppresion • Renal crisis – ACEi • GERD – PPI and behavioral change

30. Autoimmune myositis • Polymyositis (PM) • Dermatomyositis • Dermatomyositis sine myositis (just skin) • Dermatomyositis sine dermatitis (classic muscle biopsy findings) • Immune-mediated necrotizing myopathy (IMNM) • Statin exposure

31. Autoimmune myositis • Clinical presentation • Symmetric, proximal muscle weakness that develops over weeks to months • Difficulty rising from a chair, walking up steps, washing or brushing hair • If severe: dysphagia and respiratory distress from weakness of neck, pharyngeal and diapghragmatic muscles • Distal weakness very uncommon, suspect another diagnosis

32. Dermatomyositis • Clinical Presentation: Skin • Gottron papules: raised violaceous lesions at extensor surfaces of mcp, pip, dip • Gottron sign: erythematous rash at above sites • Heliotrope rash: red/purplish discoloration of eyelids

33. Dermatomyositis • Shawl sign: erythematous rash across posterior neck and shoulders • V sign: erythematous rash on anterior neck and chest • Mechanic’s hands/feet: hyperkeratotic skin thickening, often with painful cracking

34. Autoimmune myositis • Labs • Elevated CK, aldolase, AST, ALT, LD from damaged muscle cells • Auto antibodies (anti-Jo-1, anti PL-7) • ANA positive in >50% • Antisynthetase syndrome in dermatomysoitis: also with ILD, arthritis, fevers, raynaud’s • MRI: muscle edema, fascial inflammation • EMG: irritable myopathy • Muscle biopsy: generally nonspecific findings, but rules out non-autoimmune myopathies • DM: perifascicular atrophy is specific

35. Autoimmune myositis • Treatment • Glucocorticoids to control acute disease • Taper to lowest effective dose • Steroid sparing agent: MTX, azathioprine • Exercise: especially isometric, avoid heavy weight lifting

36. Autoimmune myositis vs. PMR • Polymyalgia Rheumatica (PMR) • aching and stiffness of neck, shoulders, hips (vs. weakness) • Elevated ESR >40 • Age >50 • Rapid response to prednisone 20mg/d or less • Association with GCA, but can occur independently too

37. Mixed Connective Tissue Disease • Overlap syndrome with features of SLE, Scleroderma and Polymyositis • Characteristic clinical symptoms: • Raynaud phenomenon, hand edema, synovitis, inflammatory muscle disease, sclerodactyly • High titers of anti-U1 RNP autoantibody

38. Vasculitis • Inflammatory destruction of blood vessels • Occlusion, rupture, thrombus can lead to tissue ischemia • Vary in severity and presentation based on vessels affected

40. Vasculitis • Clinical presentation • Constitutional symptoms • Subacute • Signs of inflammation • Multisystem disease • i.e. Mononeuritis multiplex • Distinct/named peripheral nerves infarcted one at a time • Due to vasculitis of vasa nervorum leading to ischemia • Hallmarks are asynchrony and asymmetry • Labs • Diagnose with biopsy • Treatment • Disease specific, often immunosuppressive therapy

41. In Summary • Suspect a rheumatologic process in patients with subacute onset of constitutional symptoms, signs of inflammation and multi system involvement • Get work-up started with thorough PE, targeted labs and xrays • Consult with Rheum and consider getting prednisone started to control acute disease, with a goal of tapering to the lowest effective dose when possible • Monitor for the longterm complications of autoimmune disease

42. Questions?