Objectives Objectives Rheumatoid Arthritis Rheumatoid Arthritis - PDF document

Objectives Objectives Rheumatoid Arthritis Rheumatoid Arthritis  Recognize and diagnose rheumatoid arthritis (RA)  Understand basic treatment approach in patients with RA  Understand the risk associated with Hareth Madhoun, DO Assistant Professor – Clinical treatment of RA Department of Internal Medicine Division of Rheumatoid - Immunology  Identity common preventative health The Ohio State University Wexner Medical Center issues that arise in care of patient with RA in primary care Epidemiology Epidemiology Synovial pathology Synovial pathology  Incidence: 0.5 per 1000 persons per year  Synovium is the primary site of  Prevalence of RA is 1% to 2% inflammation in RA.  Steadily increases to 5% in women by age 70  Normal synovium: usually discontinuous,  Risk factors: about one to two layers thick about one to two layers thick  Female are 2-3:1 compared to men  RA synovium:  Genetic factors: HLA-DR and Shared epitope  Hyperplasia, infiltrating T cells, macrophages,  Tobacco dendritic cells, B cells, mast cells  Infections (bacterial, viral)  Inflammatory cytokines  Age at onset: can occur 20-30's. Average  Extensive new vessel formation age 66 years 1

Pathogenesis of RA Pathogenesis of RA Normal Normal vs vs RA joint RA joint Therapeutic strategies for rheum atoid arthritis. Josef S. Sm olen & Günter The pathogenesis of rheum atoid arthritis: new insights from old clinical data? Steiner. Nature Review s Drug Discovery 2 , 4 7 3 -4 8 8 ( June 2 0 0 3 ) Josef S. Sm olen, Daniel Aletaha & Kurt Redlich. Nature Review s Rheum atology 8 , 2 3 5 -2 4 3 ( April 2 0 1 2 ) Diagnosis of rheumatoid arthritis Diagnosis of rheumatoid arthritis 2

Clinical features Clinical features  Vary from patient to patient  Typically slow, insidious development of symptoms  Explosive, acute polyarticular onset can occur p , p y  Monoarticular acute onset very rare Synovitis Synovitis Assessment of RA Assessment of RA  Assessment typically include clinical, functional, biochemical, and imaging parameters  Morning stiffness: > 1 hour h  Location of affected joints Polyarticular – Unsal et al. Pediatric Rheumatology 2007 5:7 doi:10.1186/1546-0096-5-7 Symmetrical – CC BY 2.0  Presence of tenderness http://creativecommons.org/licenses/by/2.0/ and swelling  Rheumatoid nodules http://generalhealthblog.com/2011/10/ morning-joint-pain-hands-mean/ 3

Assessment of RA Assessment of RA RF and CCP RF and CCP  Serum electrolytes, liver function, and  Serology not used renal function are usually normal for screening  Depressed albumin and increased  Categorize gamma globulin production gamma globulin production inflammatory inflammatory arthritis  25% of RA patients will have a  Seronegative RA normocytic normochromic anemia (chronic inflammation) http://www.mayomedicallaboratories.com/images/art  ESR and CRP are typically elevated icles/hottopics/2011/08-rheumatoid/slide15.jpg Radiological Findings in RA Radiological Findings in RA Differential diagnosis Differential diagnosis  Hands, wrists, and feet  Connective tissue diseases presenting  Periarticular osteopenia with polyarticular arthritis: Non-specific or Lupus, systemic sclerosis, mixed – – diagnostic connective tissue disease, and Sjogren's  Juxta-articular erosion (6-12 syndrome syndrome months) th )  Psoriatic arthritis  Symmetrical joint space narrowing (6-12 months) Arthritis can precede rash –  Late findings: subluxation and DIP involvement loss of joint alignment –  Other spondyloarthropathy  Crystal arthropathy Author: Bernd Brägelmann CC BY 3.0 http://creativecommons.org/licenses/by/3.0/ 4

Extra-articular Extra-articular Differential diagnosis Differential diagnosis manifestation of RA manifestation of RA  Infectious (viral)  Skin: rheumatoid nodules – Parvovirus B19  Felty's syndrome: splenomegaly with – Hepatitis C (can present with neutropenia, large granular RF+) ) lymphocytes, thrombocytopenia  Non-inflammatory conditions:  Pulmonary: pleural thickening, pleural – Fibromyalgia effusion, ILD, nodules, BOOP, Caplan's – Overuse syndromes syndrome, cricoarytenoid arthritis, PAH – Degenerative / osteoarthritis  Cardiac: pericarditis, accelerated atherosclerotic disease  Malignancy Extra-articular manifestation Extra-articular manifestation Treatment of RA Treatment of RA of RA (continued) of RA (continued)  Ophthalmologic: keratoconjunctivitis  Early treatment (rapid damage and sicca, episcleritis, scleritis, uveitis disability)  Neurologic: peripheral entrapments  Disease severity must be determined neuropathy, cervical myelopathy p y, y p y  Risk vs benefits  Risk vs benefits  Muscular: muscle atrophy, myositis  Monitoring for drug toxicity  Renal: low grade membranous glomerular  Monitoring disease activity (DAS28 nephropathy, reactive amyloid score, radiographs..etc)  Vascular: small vessel vasculitis, systemic vasculitis 5

Treatment options Treatment options DMARDs DMARDs  NSAIDs and COX-2 inhibitors: Symptomatic relief (anti-inflammatory / –  Initiation of DMARD therapy within the analgesic effects) first 3-6 months No change in disease progression – Warning: CKD, CAD, gastritis Warning: CKD CAD gastritis  Step up therapy method Step up therapy method –  Low dose prednisone: 10-15 mg daily – No change in disease progression – Bridging therapy / early adjunct therapy – Warning: diabetes, osteoporosis, weight – gain..etc. http://generalhealthblog.com/2011/10/morning-joint-pain-hands-mean/ Conventional DMARDs Conventional DMARDs Conventional DMARDs Conventional DMARDs (continued) (continued)  Hydroxychloroquine  Sulfasalazine Anti-malarial with unknown – Unknown mechanism mechanism of action – lysosomes – Reduces the development of joint Mild disease < 5 years – – damage damage ? decrease rate of structural damage – 2-3 g / day 200-400 mg daily – – Toxicity: generally safe. Sulfa allergy. Toxicity: generally safe, retinopathy / – – GI intolerance, cytopenia and corneal deposits (yearly eye exams). hepatotoxicity G6PD testing. Klipple. Primer on the rheumatic diseases, 13 th edition. 200. 138 Klipple. Primer on the rheumatic diseases, 13 th edition. 200. 138 http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new 6

Conventional DMARDs: Conventional DMARDs: Conventional DMARDs: Conventional DMARDs: Methotrexate Methotrexate Methotrexate (Toxicity) Methotrexate (Toxicity) • Dihydrofolate reductase inhibitor • Hepatotoxicity, pneumonitis, and severe • First line agent for most patient with RA myelosuppression are all very rare. • Oral or subcutaneous (15-25 mg weekly) • Alcohol intake, hepatitis serologies. GI • Very effective (monotherapy) ff ( ) intolerance, alopecia, oral ulcers – can be • Good efficacy, favorable toxicity profile, ease eliminated folic acid or SQ injections. of administration, and relatively low cost • CBC, LFT's and renal function every 2-3 months. • Slows or halts radiographic damage • No pregnancy! Klipple. Primer on the rheumatic diseases, 13 th edition. 200. 138 Klipple. Primer on the rheumatic diseases, 13 th edition. 200. 138 http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new Triple therapy Triple therapy Conventional DMARDs: Conventional DMARDs: Leflunomide Leflunomide • Dihydroorotate dehydrogenase inhibitor • Alternative oral agent to methotrexate • Does slow radiographic changes • 10-20 mg daily (loading dose 100 mg x 3) 10 20 mg daily (loading dose 100 mg x 3) • Toxicity: GI intolerance, mild hair thinning, hepatotoxicity, myelosuppression. Alcohol intake and hepatitis panel. CBC, LFT's, and renal function every 2-3 months. No pregnancy! O'dell et al. Treatment of Rheumatoid Arthritis with Methotrexate Alone, Sulfasalazine and Klipple. Primer on the rheumatic diseases, 13 th edition. 200. 138 Hydroxychloroquine, or a Combination of All Three Medications. N Engl J Med 1996; http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#new 334:1287-1291 7