Rheumatoid-arthritis-and-juvenile-rheumatoid-arthritis

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					Sean Jenkins
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Rheumatoid arthritis and juvenile rheumatoid arthritis
   1. Chronic systemic autoimmune inflamm disease. Persistent symmetric polyarithritis
      (synovitis) that affects mostly small joints of hands and feet.
   2. Most commonly affected joints: MCP, wrist, PIP, knee, MTP, shoulder, ankle, C-
      spine, hip, elbow, and temporomandibular joints
   3. Extra-articular = skin, heart, lungs, eyes
   4. Pathophysiology:
          a. External trigger necessary to start autoimmune reaction in genetically susceptible
             individuals synovial hyperplasia and endothelial cell activation inflammation
             and prolif of synovium (pannus) destruction of cartilage, bone, tendons, lig and
             blood vessels.
          b. Immune cells involved: CD4T cells, monocytes, fibroblasts, osteoclast,
             neutrophils. Bcells make Rheumatoid factor
          c. Abnormal production of cytokines leads to destructive process: TNF-, IL-1,6,8,
             TGF-, FGF, PDGF
   5. Etiology:
          a. genetic factors 50% of risk for getting RA, 60% have HLA-DR4
                  i. for juvenile idiopathic arthritis there are many genes involved,
                      IL2RA/CD25 gene and the VTCNI gene have been associated with it
          b. infectious: mycoplasma organisms, Epstein barr and rubella viruses
          c. Hormones: sex hormones play a role, more females with disease,
             hyperprolactinemia may be risk factor
          d. Immunologic factors: Thelper cells importation in initiation of RA, make IL-2 and
             INF- to activate MacP and synovial fibroblast which are the main producers of
             proinflamm cytokines (TNF- and IL-1).
   6. Pathology:
          a. Synovial membrane transformed into pannus tissue which destroys cartilage and
             bone.
          b. Autoimmune response leads to immune complexes which increase the
             inflammatory response
   7. Epidemiology: 3/10,000 , most common in 35-50yo. Women 3x more likely to get it.
      More common in native americans and less in blacks from Caribbean.
   8. Prognosis:
          a. Has exacerbations and remissions (flares)
          b. 40% get disabled after 10 yrs
          c. Ppl with double HLA-DR4 have more severe outcomes and earlier onset
          d. Also much worse with those with positive RF, early radiologic evidence of
             bony injury, persistent anemia, elevated levels of C1q component of
             complement, and presenece of anti-CCP antibodies
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          e. Myocardial infarction, myocardial dysfunction and aSX pericardial effusions
             common in RA
          f. Leading cause of mortality in RA is cardiovascular disease, then infection, then
             respiratory disease, then malignancies. If pts receive anti-TNF therapy then they
             have no increased risk for infection and malignancy
   9. Hx:
          a. Insidious onset beginning with fever, malaise, arthralgias, weakenss
          b. Get fever, morning stiffness, weight loss before joint inflame
   10. Physical:
          a. Mostly small joints of hands and feet, symmetric, swelling, tenderness, warmth,
             decreased ROM
          b. Atrophy of interosseous muscles of hand common
          c. Joint and tendon destruction deformities (ulnar deviation, boutonniere
             (flexion PIP and hyper extension DIP) and swan-neck deformities (extension
             PIP and flexion DIP), hammer toes (compensatory flexion resulting in hammer
             toes), joint ankylosis)
          d. Can also get tenosynovitis, tendon rupture, osteoporosis and carpal tunnel
             syndrome
          e. Wrists: disruption of radioulnar joint with dorsal subluxation of ulna (caput ulna),
             rotation of carpus on distal radius with unlarly translocated lunate. Ulnar drift in
             fingers and carpal raotion = zigzag deformity. May have entrapment of ulnar
             nerve at the wrist causing decreased sensation over the little finger and the ulnar
             aspect of the ring finger and decreased interosseous muscle strength and mass
          f. Elbow and shoulder: palpable snovial proliferation at the radiohumeral joint
             accompanied by flexion deformity. bursal involvement common. Tenderness,
             nocturnal pain and limited motion, rotator cuff degeneration limit abduction and
             rotation. Frozen shoulder syndrome.
          g. Feet and ankles: ankle joint rarely involved w/o MTP involvement. Midfoot and
             foot deformities loss of normal arch. MTP joint commonly deformed. Great toe
             gets hallux valgus (bunion); subluxation of the phalanx at the MTP joint of the
             other toew occurs dorsally. Hammer toes. 2nd and 3rd metatarsal heads commonly
             protrude and may become primary weight bearing surface at MTP joints.
          h. Hips and knees: commonly involved, limited motion or pain on motion and
             weight bearing. Knee effusions and synovial thickening common. Instability due
             to loss of cartilage and weakening of ligaments. Deformity= gneu valgus/varus
             and flexion deformities
          i. C-spine: neck stiffness, pain on motion, occipital headache. Usually occurs after
             having RA for >10yrs. Neurologic involvement can occur = radicular pain to
             spinal cord lesions weakness, sphinceter dysfunction, sensory deficits, and
             pathologic reflexes. Transient ischemic attacks (TIAs) and cerebrellar signs
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               reflect vertebral artery impingement from cervical subluxation or basilar artery
               impingement. Tenosynovitis of transverse lig of C1 leads to instability.
   11. Pain, stiffness, joint enlargement:
          a. Stiffness due to change in articular surface or soft tissue contractures, doesn’t
               change with time of day (unlike OA). Enlarged synovial mem, periarticular
               ligaments, supporting structures major pain-sensitive structures. >10% of pts with
               RA get deformity of small joints of hand w/in 2yrs, 33% get them over time.
   12. Nonarticular RA involvement:
          a. Increased cardiovascular morbidity. Keratoconjunctivitis siccia is common in
               RA pts, often the initial manifestation of secondary Sjogern syndrome
          b. Lungs: pleural effusions, interstitial fibrosis, caplan syndrome (nodules in
               lungs) and bronchiolitis obliterans organizing pneumonia.
          c. Liver: affected in Felty syndrome
          d. Rheumatoid nodules in 25%
          e. Nerve entrapment is common (median nerve in carpal tunnel syndrome
          f. vasculitic lesions of skin
          g. palmar erythema
   13. 2010 RA classification criteria
          a. Ppl with at least 1 joint with synovitis, those whose synovitis is not better
               explained by another disease (lupus, psoriatic arthritis, gout) should be tested
          b. Score made based on: joint involvement, serology test results, acute phase
               reactant test results, and patient self-reporting of signs/symptom duration
                    i. 6/10 or > = RA
                   ii. 1 large joint = 0
                  iii. 2-10 large joints = 1
                  iv. 1-3 small joints = 2 points
                   v. 4-10 small joints = 3 points
                  vi. >10 joints= 5 points
          c. At least 1 serology test needed
                    i. Negative RF and negative ACPA = 0 points
                   ii. Low-positive RF or low-positive ACPA = 2 points
                  iii. High-positive RF or high-positive ACPA = 3 points
          d. At least 1 acute phase reactant test needed
                    i. Normal CRP and normal ESR = 0
                   ii. Abnormal CRP or abnormal ESR = 1
          e. Patient reported duration
                    i. <6 weeks = 0
                   ii. >6weeks = 1
   14. Measurement of progression
          a. Stage 1: early RA, no destructive changegs
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          b. Stage II: moderate progression, x-ray evidence of periarticular osteoporosis, w/
              or w/o subchondral bone destruction, cartilage destruction. Joint ROM limited but
              no deformities. Muscle atrophy, can have extra-articular soft tissue lesions.
          c. Stage III: severe progression. X-ray shows cartilage and bone destruction and
              periarticular osteoporosis, joint deformity w/o fibrous or bony ankylosis.
              Extensive muscle atrophy. Can have extra-articular soft tissue lesions
          d. Stage IV: terminal progression. Has fibrous or bony ankylosis and everything
              else from stage III
   15. Measurement of functional status:
          a. Categorized into 4 classes
                   i. Class I: completely able to do everything
                  ii. Class II: able to do usual self-care and vocational activities but limited
                      avocational activities (ex hobbies)
                 iii. Class III: do usual self care but can’t do vocational activities (can’t do ur
                      job)
                 iv. Class IV: can’t do usual self care
   16. Measurement of disease remission: must meat at least 5 for 2 consecutive months
          a. Duration of morning stiffness <15min
          b. No fatigue
          c. No joint pain
          d. No joint tenderness or pain with motion
          e. No soft tissue swelling in joints or tendon sheaths
          f. ESR <30mm/h in a female and <20mm/h in male
          g. Predictors for remission of RA
   17. Differential DX:
          a. Fibromyalgia                                        h. Gout/pseudogout
          b. Lyme disease                                        i. Polymyalgia rheumatic
          c. Myelodysplastic syndrome                            j. Psoriatic arthritis
          d. OA                                                  k. Sacroidosis
          e. Degenerative joint disease                          l. Sjogren syndrome
          f. Paraneoplastic syndromes                            m. Systemic lupus
          g. Polychondritis                                         erythematosus
   18. DX evaluations for RA
          a. RF tests: not specific for RA, in 60-80%
          b. Antinuclear antibodies (ANA): present in 40% with RA
          c. Anti-cyclic citrullinated protein (anti-CCP): same sensitivity and specificity as
              RF, better test for early RA
                   i. If + for both anti-CCP and RF high likelihood for RA
          d. Imaging: X-ray most common, MRI more sensitive but $, important of cervical
              subluxation. Bone scan only used to determine degree of inflamm
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   19. Tx:
          a. Meds: NSAIDs, DMARDs, immunosuppressants, biologic response modifiers,
              corticosteroids
                   i. Early use of DMADs for 2-3 months standard b/c slows progression and
                      may induce remission, if delay 2-3 mo leads to irreversible joint damage
                  ii. Xenobiotic DMARDs: gold salts, D-penicillamine, choloquine and
                      hydroxychloroquine, sulfasalazine, methotrexate, azathioprine,
                      cyclosporine A
                          1. Methotrexate (MXT); folic acid antagonist, start low does and
                              increase w/in 4-6 weeks. 1% get pneumonitis. Don’t use if
                              pregnant b/c of teratogenic effects
                          2. Leflunomide: blocks autoimmune antibodies and reduces
                              inflamm. Don’t use when pregnant
                          3. Don’t really use gold salts
                          4. May cause bone marrow toxicity, renal, allergic skin rxns,
                              infections
          b. Surgical: synovectomy, tensosynovectomy, tendon realignment, reconstructive
              surgery, arthroplasty, arthrodesis
          c. Biological agents:
                   i. TNF- blockers: etanercept (inhibiting TNF), infliximab, adalimuab
                      (recombinant human IgG monoclonal ab specific for TNF), golimumab
                      (monoclonal antibody), rituximab (monoclonal antibody used in combo
                      with methotrexate)
                  ii. IL-1-induced cytokines: anakinra (IL-1 receptor antagonist, occupies
                      the receptor without triggering it), abatacept (selective co-stim modulator
                      that inhibits T cell activation by binding CD80 and 86 and blocking
                      interaction with CD28, tocilizumab (IL6 receptor inhibitor, use for
                      moderate to severe RA)
                          1. Adverse effects: emergence of antinuclear antibodies, drug
                              induced lupus like syndromes, infections
          d. NSAIDs and steroids:
                   i. glucocorticoids (anti-inflamm) used til DMARDs are effective. Not used
                      longer cause lots side-effects with long term use
                  ii. NSAIDs: interfere with prostaglandin synth by inhibiting COX
          e. Combo therapy: usually MTX and some of the other treatments listed
   20. Juvenile Rheumatoid arthritis:
          a. Most common form of childhood arthritis, different outcomes from adult onset
              RA. Considered juvenile if get <16yo and duration is >6weeks. 3 sub types:
                   i. Polyarticular (>5 joints)
                  ii. Pauciarticular (1-4)
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                    iii. Systemic (constitutional sx and joint involvement)
          b.     IL2RA/CD25 gene and the VTCN1 gene are associated with this
          c.     Humoral and cell mediated immunity involved. Basically the same as regular RA
          d.     Epidemiology: 300,000 kids in US, 4-14/100,000 annually. Oligoarticular is the
                 most common, followed by polyarticular RF negative. Girls 3x more likely to get.
                 Highest frequency in kids 1-3 yo
          e.     Prognosis: those with polyarticular have problems throughout life, those with
                 oligoarticular have eventual permanent remission. Kids at less risk for lung
                 involvement and vasculitis than adults.
          f.     Hx: insidious onset with morning stiffness or gelling phenomenon (stiffness after
                 long periods of sitting), and arthralgia occurring later in day. Kids often stop
                 using joints normally.
                      i. Systemic onset has fevers, evanescent rash salmon colored on trunk and
                         extermities,
                     ii. Enthesitis related arthritis presents at night and after exercise. Usually as
                         butt pain and back pain that improves with activity
          g.     DX features: RH test, 70% + for ANA assay which is a marker for increased risk
                 of anterior uveitis. MIR best imaging technique b/c can detect synovial
                 hypertrophy, soft tissue swelling and can determine status of overall joint. Limbs
                 with synovitis are usually held in flexion
          h.     Systemic arthritis: appear systemically ill, have arthralgia, generalized myalgia,
                 evanescent, salmon macular rash on trunk and extremities, hepatosplenomegaly,
                 sometimes lymphadenopathy (axillary nodes). May have serositis
          i.     Oligoarticular: large weight bearing joints affected (knee and ankles).
                 Involvement of small joints in hands atypical. Anterior uveitis present in 20%
                 especially those with ANA +
          j.     Polyarticular: 5> joints affected w/in 6 mo after onset. Usually weight bearing
                 joints, may have rheumatoid nodules in those with RF +, often symmetrical
                 involvement of small joints of hands.
          k.     Psoriatic arthritis: psoriasis occurs after mild arthritis in ½ kids. Most
                 monoarticular, DIP, tenosynovitis. Majority have nail involvement but isn’t
                 specific to this disease. About half have disordered bone growth and shortening
          l.     Enthesitis related arthritis: periods of inflamm of tendons and ligaments. Pain
                 and tenderness are most common sx, but may have swelling. May have dactylitis
                 (sausage fingers) and asymmetric oligoarticular arthritis of lower limbs. Later
                 axial involvement occurs. Must have 2/5 of the following
                      i. Sacroiliac tenderness and/or inflammaotyr lumbosacral pain
                     ii. Positive HLA-B27
                    iii. Onset of arthritis in male >6yo
                    iv. Acute symptomatic anterior uveitis
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                 v. Presence in a first-degree relative of ankylosing spondylitis, enthesitis-
                     related arthritis, inflammory bowel disease with sacroiliitis, reactive
                     arthritis, or acute anertior uveitis.
          m. Tx:
                  i. NSAIDs, DMARDs, biological agents, intra-articular and oral steroids
                 ii. Psycosocial factors (counseling for pts and parents and teachers
               iii. Nutrition, address anemia, generalized osteoporosis
                iv. PT
                 v. Occupational therapy
                vi. Pts with 4 or < joints: NSAIDs alone may be good enough, intraarticular
                     injection of triamcinolone, MTX for those with high disease activity, use
                     sulfasalazine if don’t have response with mtx
               vii. Pts 5 or >: may start tx with MTX or leflunomide, may use TNF-
                     inhibitor if no response to MTX. If that doesn’t work use rituximab
              viii. Active sacroiliac arthritis: TNF- inhibitor
                ix. Systemic arthritis: started on steroids or anakira. Can use tocilizumab for
                     monotherapy or in combo with TX for kids >2yo. If no systemic features
                     present NSAIDs may be effective, after 1 mo use MTX , if after 3 mo no
                     improvement may add TNF-
                 x. macP activation syndrome: complication of systemic RA with
                     hypofibrinogenemia, thrombocytopenia and elvated aspartate
                     aminotransferase. Use cyclosporine A or anakinra.
                xi. Uveitis: topical corticosteroids and mydriatic agents. May use MTX or
                     cyclosporine to control. Infliximab used for those resitant to
                     immunosuppressive agents.

				
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