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Flashcards in Rheumatoid arthritis Deck (13):
1

Rheumatoid arthritis (RA)

-Chronic inflammatory systemic disease w/ major target being synovial joints
-Joint involvement is symmetrical, sex ratio is 2-6:1 (F:M) for adults
-Genetics: having the alleles HLA-DR4 or HLA-DRB1. All of the implicated alleles have a shared epitope (QR/KRAA) which confers greater risk of developing RA
-Etiology is unknown but implicated is EBV, other viruses, E coli and other bacteria

2

Pathogenesis of RA 1

-Synovial inflammation and proliferation mediated by humoral and cellular responses
-Initiated from unknown source but the synovial macrophages and dendritic cells function as APCs
-Infiltration of mononuclear and polynuclear leukocytes, w/ large release of cytokines
-Most important cytokines: IL1, IL6, and TNFa
-B cells produce rheumatoid factor (RF) and complement components

3

Pathogenesis of RA 2

-Granulation tissue forms at edge of the synovial lining (pannus) w/ extensive angiogenesis
-Pannus grows over, invades, and erodes cartilage
-Macrophages and fibroblasts elaborate matrix metalloproteinases
-Osteoclast differentiating factor, IL1 and TNFa contribute to macrophage differentiation into osteoclasts
-Together this process results in loss of ECM, bone, and tissue damage

4

Rheumatoid factor (RF) and resulting pathogenesis

-Antibody (polyclonal, IgM or IgG) is made against other IgGs (the Fc portion)
-Found in 80% of pts w/ RA
-The binding of self-associating Abs to IgGs leads to immune complex formation and activation of complement
-immune complexes are phagocytosed by PNS which release their lysosomal nzs
-Chemotactic factors from complement activation (C5a) attract more leukocytes

5

ACCP and other immune complexes

-Anti-cyclic citrullinated protein (ACCPs) are antibodies against cyclic citrullinated proteins
-More specific test than RF (87% of RA are positive ACCP), since RF can be from other diseases like hepatitis and endocarditis
-Arginine containing Ags (from smoking) can induce citrullined proteins and initiate an immune response against ACCPs
-Immune complexes against nuclear components are observed as well

6

Tissue damage in RA

-Bone resorption (local= erosion, genera= osteopenia) mediated by osteoclasts via osteoclast-differentiating factor, IL1, and TNFa
-Reduction of cartilage thickness, secondary osteoarthritis
-MCPs, PIPs most affected, DIPs spared
-Boutonniere deformity: PIP joint flexion w/ DIP hyperextension
-Swan neck deformity: PIP joint hyperextension w/ DIP joint flexion
-Ulnar deviation of fingers, MCP/MTP subluxation, pronation of feet
-Ankylosis (bone fusion)

7

Joint findings in RA

-Joint swelling, pain and stiffness
-Increased temp and erythema
-Decreased range of motion and joint contractures

8

Extraarticular RA manifestations

-Most pts have some osteopenia or osteoporosis
-Many have anemia (due to chronic disease): normocytic, normochromic
-Muscle atrophy, from disuse or rheumatoid myopathy
-Rheumatoid nodules: painless granulomas in pressure areas (signify more severe disease)

9

Immune complex depositions in extraarticular tissue 1

-Relatively rare but most notable is vasculitis, resulting in ulcers, digital gangrene, and neuropathy
-Damage due to vascular obstruction and infarction
-Pleuropulmonary manifestations can include effusion, restrictive lung disease and rheumatoid lung nodules
-Pericarditis usually w/ small effusion

10

Immune complex depositions in extraarticular tissue 2

-Peripheral nerve compression (CTS) or SC compression (cervical subluxation at C1-C2)
-Ocular inflammation: episcleritis, rarely scleromalacia (perforation of sclera), and more rarely keratomalacia (corneal melt)
-Sjogren's syndrome: inflammation of salivary and lacrimal glands (causing dryness)
-Secondary amyloidosis (rare)
-RA is associated w/ premature CVD and some cancer

11

Juvenile idiopathic arthritis (JIA)

-Modes: polyarticular (40-50%), rarely RF+, less frequent nodules, but largely similar to adult RA
-Monarticular or oligoarticular (30-40%): only one joint inflamed @ onset, but upto 4 joints affected later
-Substantial portion of these pts get iridocyclitis (infection of ant. chamber of eye)
-Systemic/acute febrile onset (10%): pts have high fever, rash, hepatosplenomegaly, carditis and LAD, along w/ joint inflammation
-Many children w/ JIA have stunted growth/other growth abnormalities

12

JIA lab tests

-ESR (elevated), C-reactive protein (CRP) elevated, synovial fluid analysis
-RF (rarely + in JIA), ACCP
-Positive ANA
-Radiographs

13

Rx of RA

-Education
-NSAIDs
-DMARDs: hydrochloroquine, salfasalazine, methotrexate (combinations)
-Biologics: TNFa-antibodies (etanercept), IL1 receptor antagonists (Anakinra), anti-CD20 (rituximab), IL6 blocker (Tocilzumab)
-Corticosteroids: usually intraarticular injections
-PT/rehab
-Reconstructive surgery
-Prognosis: good if caught and Rx early