• 1% of population, one of most common autoimmune dz
• lower prevalence in Asian population
• female to male ratio 3:1
• most common onset: 3rd-5th decades (20-40)
• trigger in susceptible host is unknown

• Human leukocyte antigen (HLA) DR4 is a genetic risk factor
• those with this marker usually have a more serious form, seropositive (+RF)

• synovium is infiltrated with mononuclear cells (monocytes, T lymphocytes) causing it to become thick and inflamed
• Cartilage is worn down and joint space is narrowed
• Joint swells, is edematous, warm, tender, and may have effusion
• Pannus invades at the meeting of bone-cartilage-synovium, causing progressive destruction of bone and cartilage

• grossly palpable subcutaneous nodules
• found in synovium and other tissues
• often at elbow and along extensor tendon surfaces (ulna), less common in lungs, pleura, pericardium sclerae, heart
• large granulomas
• areas of central necrosis surrounding mononuclear cells
• outer layer of histiocytes (macrophage)

- an immunoglobulin M (IgM) which attacks IgG and other antibodies (including those to matrix degradation products)

- enters the synovial fluid and forms complexes
- causes more inflammatory immune cascades to occur

- not necessary or sufficient for dx of RA

- other dz (like lupus) are associated with +RF

- 10-20% of RA pts are RF-

- +RF pts are likely to have more severe form of RA 

• Normally just a few cell layers thick
• in RA, becomes palpable on exam (synovitis)
• causes prolonged morning stiffness, >1hr (often several) is classic for RA
• sxs improve with moderate activity

• Ulnar deviation at MCP joints
• volar subluxatio at MCP joints
• flexion and extension contractures in the PIP and DIP joints of the fingers
• Lead to SWAN NECK deformity 
• Boutonniere deformity
• erosion of ulnar styloid (can cause sharp bony prominences and rupture of extensor tendons)
• synovitis at wrists: median nerve compression & carpal tunnel syndrome

• caused from rupture of synovial fluid from knee into calf
• can look like thrombophlebitis or cellulitis

• multiple pulmonary nodules in RA
• Pneumoconiosis (restrictive lung dz)
• Acute interstitial lung dz can be associated with pulmonary hemorrhage

• Associated with circulating complexes of IGg and RF
• leads to cutaneous lesions:
  • ulcers
  • skin necrosis
  • mononeuritis multiplex
  • intestinal infarction

Sjogrens syndrome

carpal tunnel syndrome

Felty's syndrome

Bakers cysts

vasculitis

• autoimmune disorder that presents with dryness of eyes (keratoconjunctivitis sicca) and mouth (xerostomia) due to immune-mediated dysfunction of the lacrimal and salivary glands, which can become enlarged
• associated with various autoantibodies (ANA, RF, Anti-SS-A, Anti-SS-B)
• associated with systemic clinical features: interstitial lung dz, vasculitis, lymphoma
• 1° seen in women (9:1), between 40-60 yo
• can occur in isolation (primary) or in association with another rheumatic dz,most commonly RA (secondary)

• present in most pts with RA
• most helpful when looking for cause of previously undiagnosed inflammatory arthritis
• 95% specific for RA

• common in RA but not dx helpful
• 30-60% of RA pts have high titers
• 95-100% of SLE pts have +ANA 
• also + in Sjogrens, scleroderma polymyositis

OA: spares wrist and MCP joints

Gouty arthritis: synovial crystals

Chronic lyme arthritis: usually only one knee, get serology

Hep C: anti-CCP negative, but can be +RF

SLE: malar rash, photosensitivity, high dsDNA, glomerulonephritis, CNS abnormalities

1. NSAIDS: never used as monotherapy, help with pain, inflammation, can help ↓ pain until DMARDs take effect. Help with daily fxn, but not underlying dz process
2. Corticosteroids: for flare ups
3. DMARDS (disease modifying anti-rheumatic drugs): 1° drugs uses

• GI toxicity (bleeding, ulcer perf)
• Platelet inhibition
• decrease in renal blood flow (dangerous if renal stenosis is present)

(all consequences of prostaglandin synthesis inhibition)

Large doses required: 

Aspirin: 12-16 tabs per day

Ibuprofen: 2400-3200 mg/d

• aka SAARDS (slow acting antirheumatic drugs)
• may take weeks/months to benefit from the effects of these drugs
• most inhibit progression of erosive dz
• Ex: Methotrexate, Leflunomide, Hydroxychloroquine (plaquenil), sulfasalazine, gold, minocycline, cyclosporine, etc
• Triple therapy of methotrexate, hydroxychloroquin and sulfasalazine sometimes used 

Teratogenic

Hematologic

Pulmonary

Hepatic (cirrhosis)

• Hydorxychloroquine has lowest toxicity, but less effective for gevere dz (slow onset of action)

• classified as antimalarial
• useful in treating several forms of malaria, as well as rheumatic diseases such as RA and SLE
  • particularly relieves skin inflammation, hair loss, mouth sores, fatigue, and joint pains
  • helps prevent relapses of active dz

• cyclophosphamide, azathioprine and cyclosporine
• risk of infections
• cyclophosphamide and azathioprinealso have risk of bladder and lymphoid malignant dz

Anti-cytokine-directed therapies

• newest and most effective agents
• ex: Etanercept (Enbrel): inhibits TNFa
• extremely effective in controlling dz
• stops progression of bony erosive dz
• given by sc injection twice per week
• very expensive

Leflunomide (Arava)

• used as adjunct to methotrexate
• An oral DMARD
• reduces inflammation in joints, which is responsible for both the symptoms and progression of RA
• Unique mech: Inhibits dihydroorotate dehydrogenase (which is necessary for DNA & RNA synthesis), thereby suppresses the immune cells responsible for inflammation

• Very expensive
• Infliximab and etenercept: have increased risk of infection, esp reactivation of pulmonary TB

- sometimes needed for tmt of RA
- prednisone: 5 mg/d or > has dramatic effects within 1-2 days
- Side effects: osteoporosis, pathologic fx, avascular necrosis of bone
- give calcium, biophosphonates and vit D to counteract these effects
- can use intraarticular steroid injections if only a few joints are involved (highly efficacy, few side effects) can only give 4x year

• joint replacement: for severe destructive dz, esp in knee and hip
• Reconstructive: done early in hand and foot, can improve fxn, often prevents deformity and tendon rupture

PT: muscle strengthening, conditioning; maintains joint mobility; splints (wrist) at night prevents deformities

OT: appliances protect joints make daily activities easier; velcors, grips for pens, raised chairs, toilets