Rheumatoid arthritis

Question 1

Rheumatoid arthritis (RA)

Answer 1

• 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

Question 2

Pathogenesis of RA 1

Answer 2

• 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

Question 3

Pathogenesis of RA 2

Answer 3

• 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

Question 4

Rheumatoid factor (RF) and resulting pathogenesis

Answer 4

• 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

Question 5

ACCP and other immune complexes

Answer 5

• 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

Question 6

Tissue damage in RA

Answer 6

• 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)

Question 7

Joint findings in RA

Answer 7

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

Question 8

Extraarticular RA manifestations

Answer 8

• 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)

Question 9

Immune complex depositions in extraarticular tissue 1

Answer 9

• 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

Question 10

Immune complex depositions in extraarticular tissue 2

Answer 10

• 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

Question 11

Juvenile idiopathic arthritis (JIA)

Answer 11

• 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

Question 12

JIA lab tests

Answer 12

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

Question 13

Rx of RA

Answer 13

• 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