Rheumatoid Arthritis - Clinical Aspects and Treatment Lecture Powerpoint Flashcards
Rheumatoid arthritis definition
Chronic inflammatory polyarthritis characterized by morning stiffness with symmetrical distribution often involving the hands, can also affect extra articular organ systems (rheumatoid disease), its natural history can be variable but often characterized by exacerbation and remissions
Rheumatoid arthritis etiology
- unknown
- Infectious agents such as parvovirus B19 (5th dz)
- cigarrete smoke
- periodontitis
Rheumatoid arthritis pathogenesis
Unknown antigen stimulus in a genetically predisposed individual leads to loss of tolerance with an autoimmune response with a self sustaining inflammatory reaction and recruitment of APC and T cells. Macrophage and T cells release cytokines, many are pro inflammatory, B cells differentiate into plasma cells after being stimulated by T cells to produce immunoglobin rheumatoid factor antibodies, osteoclast activation leads to bone resorption, the synovium becomes a pannus, cartilage destruction and ligament laxity
Pannus
Locally invasive proliferation of tissue damaging things around it (similar to a malignancy in the local damage it propagates but does not metastasize in any way)
___ involvement is common in almost all rheumatoid arthritis
Hand
Rheumatoid arthritis pattern of onset
-insidous onset over weeks to months sometimes beginning asymmetrically but most often symmetric, can see constitutional symptoms, acute onset has better prognosis,
Poor prognostic signs of rheumatoid arthritis (4)
- Earlier age of onset
- insidious onset
- extra-articular manifestations
- high titer of rheumatoid factor
Elevation of platelet counts can indicate ___ similarly to a sedrate
inflammation
Mortality in rheumatoid disease
Early mortality noted in several studies, median life expectancy decreased by 7 years in males and 3 in ffemales, increased incidence of myocardial infarct, stroke, risk of lymphoma
Clinical findings of rheumatoid arthritis by joint (cervical spine, shoulder, elbows, wrist and hands, knees, ankles and foot)
- Atlantoaxial sublaxation
- rotator cuff tears
- loss of complete extension of elbows
- synovitis of dorsum of wrist, ulnar deviation, swan neck and boutonniere deformities, carpal tunnel syndrome
- Quad atrophy, flexion contractures
- eversion or pronation of ankle, cocked up toes
Vaughan jackson deformit
Tear of extensor tendons of 4th and 5th finger due to erosive disease at the distal ulna creating benedictine sign, requires ortho referral for reattachment
Felty’s syndrome triad
Splenomegaly, rheumatoid arthritis, and neutropenia, associated with infections and leg ulcerations
Extra-articular manifestations of rheumatoid arthritis (5)
- vasculitis
- pericarditis
- pleuritis
- pulmonary nodules
- sjogren’s
4 goals of Rheumatoid arthritis treatment
- diminish symptoms
- maintain function
- institute agents early in course of disease which prevent joint damage
- minimize toxicity of treatment modalities
Rheumatoid arthritis treatment options
- exercise
- good primary and preventive care against weight gain, tobacco,hypertension, etc
- NSAIDS to initially control symptoms, does not alter course of dz
- glucocorticoids (when NSAIDS inadequate, keep dosage low to control flares, bridge therapy when starting DMARDs), can be systemic or intra-articular
- DMARDs (considered in anyone with ongoing active disease, potentially reduce or prevent joint damage, timing is important
Examples of nonbiologic DMARDs (4)
- methotrexate
- hydroxychloroquine
- azathioprine (imuran)
- leflunomide (arava)
Methotrexate mech of action, administration, ADR’s (4)
Antimetabolite inhibits dihydrofolate reductase interfering with purine synthesis taking 1-2 months to see benefit with 60-75% response rate
- 10-25mg weekly oral (GI upset concern) or SQ better
- hepatotoxic, cytopenias, teratogenic in pregnancy, requires folic acid supplement
Hydroxychloroquine big ADR
-Retinal pigmentation around macula interfering with central vision
Sulfasalazine (azulfidine)
Sulfa agent and aspirin combination that is immunosuppresive helpful for some patients with RA sometimes alongside methotrexate and hydroxychloroquine seeing effects in 4-6 months
Leflunomide (arava) mech of action and ADR’s (3)
- Pyrimidine synthesis inhibitor most active in 50% of patients after 6-12 months, better tolerated than methotrexate in some cases
- fetal abnormalities for years in women who may become pregnant, hepatotoxic, weight loss
TNF blocking agents for RA treatment (5)
- Etanercept
- infliximab (remicade)
- adalimuma (humira)
- certolizumab (cimzia)
- golimumab
Biological DMARDs and serious infections
No objective evidence but clinical practice shows there can be development of serious infections mostly of respiratory tract, skin, and urinary tract while on biologic agents, temporary discontinuing biologic around time of infection and then resuming after is often seen as best practice, can see reactivation of Tb or latent disease rarely (corticosteroid use bigger risk)
Biological DMARDs and malignancy
Only nonmelanoma and melanoma skin cancers have been shown to be increased in those on biological DMARD’s, partial contraindication
Biological DMARDs and MS
Contraindicated use
Biological DMARDs and heart failure
Contradinicated in use
Drug induced lupus syndrome
A side effect of use of biological DMARDs in some cases that causes symptoms similar to lupus but reverse upon discontinuation of the offending agent
Rituximab (rituxan) mechanism of action, administration, ADR’s (3)
- selectively depletes cd20 B cells
- given IV over course of 2 infusions 2 weeks apart lasting up to 6 months +
- infusion rxn, increased risk of infection, progressive multifocal leukoencephalopathy in patients with SLE
List 3 janus kinase inhibitors and what is a complication (1)
- tofacitinib
- baricitinib
- upadacitinib
-herpes zoster infection
