Flashcards in Rheumatoid Arthritis Deck (23):
Epidemiology of RA
•Most common type of polyarthritis. 3x more common in women. 1% total population.
•Peak onset in 3rd to 5th decade
2 risk factors for RA
Tobacco and HLA-DRB1 (shared epitope)
Pathogenesis of RA
Synovial membrane cells proliferate into a pannus rich w/ macrophages, fibroblasts, PMNs, B cells, plasma cells, and T cells. Vascular proliferation permits increased cell trafficking. Cytokines are released, MMPs break down bone / cartilage
5 diagnostic criteria for RA
•Must have synovitis w/o other cause
•RF / CCP (more specific). High titer is >3xULN.
•Increased ESR / CRP
What joints are usually involved in RA? Which are not involved?
Usually involves PIPs, MCP, wrist, and MTP.
Usually does NOT involve hips, DIPs, and lumbar spine.
ESR vs CRP
ESR reflects 1 month, CRP reflects days.
Extra-articular / systemic manifestations of RA
Moderate / severe
•Mild: rheumatoid nodules, nail fold infarcts, iron deficiency anemia, Raynauds, Sjogrens
•Moderate / severe: scleritis, interstitial lung disease, pericarditis, pleuritis, vasculitis (may cause ulcers), Felty syndrome (neutropenia + splenomegaly), nerve impingement from cervical spine disease, premature CVD (due to systemic inflammation)
Treating acute RA (3)
•NSAIDs – naproxen is good to start with.
•Prednisone – use while DMARDs kick in. Good for flares. Extra-articular disease requires higher dose.
•Steroid injections if only a few joints are involved.
What does DMARDs stand for?
Disease modifying anti rheumatic drugs
Methotrexate, leflunomide, Sulfasalazine, and hydroxchloroquine.
•Mechanism – inhibition of dihydrofolate reductase blocks purine synthesis. Blocks cells w/ high turnover.
•Toxicity – TERATOGEN, CIRRHOSIS (esp w/ ETOH), oral ulcers, GI, cytopenias, cough / SOB (lung hypersensitivity), infection
•Requires daily folic acid. Monitor CBC, liver, kidney. Get baseline LFTs, Hep B / C, and CXR.
How is drug eliminated quickly?
•Mechanism – inhibits dihydroorotate dehydrogenase → stops pyrimidine / purine synthesis → stops proliferation of T cells.
•Toxicity – Teratogen, GI, alopecia, HTN, cytopenias, liver toxicity (esp w/ alcohol), infection
•Requirements: Monitor CBC, liver, kidney. Get baseline Hep B / C and CXR.
•Give cholestyramine in hospital for px w/ infection to get rid of drug quickly
Safe with what?
•Mechanism – AB and anti-inflammatory
•Toxicity – GI, liver toxicity, aplastic anemia, nephritis syndrome, pancreatitis, headache. Contraindicated w/ sulfa allergy.
•Safe w/ pregnancy and alcohol.
•Monitor CBC, liver, and screen for G6PDH
•Use – Mainstay for lupus. Used for very mild RA.
•Mechanism – mild antimalarial that stablizes lysosomes, inhibits DNA polymerase, decreases fibronectin / platelet aggregation / histamine / IL1 cellular inflammation and destruction. Does NOT cause immunosuppression.
•Toxicity – retinal toxicity, pigment, neuromyopathy
•Monitor visual field testing every 1-5 years
Works as well as what?
Mtx, Ssz, Hcq.
Works as well as TNF-inhibitor
4 monoclonal Abs
1 soluble receptor drug
•Monoclonal Abs: infliximab, adalimumab, golimumab, certolizumab
•Etancercept is soluble receptor
4 risks of TNFa Inhibitors
•Infection – may not mount high fever, atypical / fungal infection, disseminated TB (TB test should be done before starting anti-TNF)
•Malignancy – nonmelanoma skin cancer, lymphoma
4 non-TNF biologics
Abatacept, rituximab, tocilizumab, tofacitinib
Pro / con
CTLA4 blocks T cell co-stimulation.
Lower infection risk than anti-TNF, but takes 4 months to work
Anti-CD20 Ab depletes naïve B cells.
Risk of Hep B reactivation and progressive multifocal leukoencephalopathy (PML, brain infection)
Anti-IL6, which normally triggers cartilage destruction
JAK kinase inhibitor.
Risk of EBV-related malignancy
4 general risks of biologics
•Injection / infusion rxns due to being foreign molecules
•Predisposition to infection. Avoid live vaccinations. Evaluate fever / monoarthritis.
•Non-melanoma skin cancer
•Biologics should not be combined. May be used w/ DMARDs.