rheumatoid_arthritis by dandanhuanghuang



9/16/2011     Dr. Alka Stoelinga   1

• Autoimmune disorder of unknown etiology
• Occurs as a result of chronic dysfunction of
  exocrine glands and is characterized by:
      – Dryness of mouth, eyes, and other areas covered
        by mucus membranes
• Onset:40-50 years
• F:M=9:1

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                   Clinical features:
 Salivary gland and lacrimal glands are mainly affected
1. Salavary gland enlargement
• Decrease salivary secretion—Dryness of mouth i.e Xerostomia
   leading to difficulty in speaking and swallowing, and to severe
   dental caries. There may be loss of taste and smell
• Decrease tear production
• Keratoconjunctivitis sicca– Results from inadequate tear
   production caused by lymphocyte and plasma cell infitration
   of lacrimal glands
3.Pancreatitis,Pleuritis,neuropsychiatric dysfunction and
   vasculitis may be present.
4.Renal tubular acidosis and chronic interestitial nephritis may
   also occur.
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    Revised Classification Criteria for Sjögren's Syndrome
• SS diagnosis requires the presence of signs, symptoms, and lab findings.
• Patient-reported symptoms must include
      1.    ocular symptoms, such as daily, persistent, troublesome dry eyes for more
            than 3 months, and
      2.    oral symptoms, such as needing to drink water to swallow food.
•     Signs
     –      Positive Schirmer's test
• Histopathology studies should show
      – Focal lymphocytic proliferation (Sialadenitis)
      – Ultrasound examinations The parenchyma of the gland demonstrates
        multiple, small-2-6 mm hypoechoic lesions (lymphocytic infiltrates). Sialectasis
        with calculi are demonstrated if the disease is advanced
      – Parotid sialography, or salivary scintigraphy (Widespread puddling of the
        injected contrast scattered throughout the gland)
      – Autoantibodies against Ro (SSA) and/or La (SSB) antigens

9/16/2011                              Dr. Alka Stoelinga                               4

1. Autoantibodies:
• Rheumatoid Factor
• Anti-Ro, Anti-La
2. Schirmer’s test
• To determine/demonstrate decrease tear
3. Raised ESR
4. Salivary gland biopsy
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• Artificial tear drop
• Oral gel for soothing effect
• Prednisolone
3. Immunosuppressive
• Methotrexate
• Azathioprine
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•   Rheumatoid arthritis
•   Seronegative spondarthritis
•   Crystal-associated disease
•   Joint infection
•   Juvenile idiopathic arthritis

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     Look and Evaluate first for
1.         Distribution of joint involvement
       –          Four basic patterns
              •        Polyarticular symmetric – RA, SLE
              •        Monoarticular arthritis – OA, Gout, Septic arthritis
              •        Oligoarticular asymmetric- Spondyloarthropathis- AS
              •        Migratory arthropathy- RF, Gonococcal arthritis, Lyme disease
2.         Acute or Chronic
       –          Acute -Crystal induced arthritis (Gout, pseudogout), Septic arthritis
       –          Chronic -OA
3.         Evidence of systemic Manifestations
       –          SLE – Skin, Lungs, Kidney, CNS, Hematologic manifestations
       –          Systemic sclerosis- Skin+ Raynaud’s phenomenon
       –          Sjögren's syndrome- Keratoconjunctivitis sicca+ Parotid enlargement
       –          Wegener’s granulomatosis - Upper and lower RTI+ Renal involvement
       –          OA- No systemic symptoms
4.         Evidence of Inflammation
       –          Joint inflammation- RA
       –          No joint inflammation- OA, Osteoporosis
5.         Findings
       –          Morning stiffness >1 hr
       –          Red, warm, erythematous joints
       –          Elevated ESR

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            Rheumatoid arthritis

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• A 30 year old woman presents with 3 week
  h/o joint swelling and stiffness. She points to
  her PIPs and MCPs and wrists. She informs
  that the stiffness lasts for around 2 hrs every
  morning and symptoms improves as the day
  progresses. She denies back pain/ stiffness.
  She has fatigue and low grade fever, Swollen
  and reddened MCPs and PIPs, DIPs wnl. Fluid
  in wrist joints. Other examinations are wnl.

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             Rheumatoid arthritis
• Chronic inflammatory multisystem disease with
  main target being synovium.
• Non suppurative, proliferative inflammation of
• Progresses to destruction of the articular
• Cause bone erosions
• Deform joints
• Ankylosis ( stiffness ) of the joints.
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• Inflammatory synovitis
• Presenting in symmetrical distribution

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            Diagnostic criteria for rheumatoid arthritis
Four of the following criteria must be met:
   –   Morning stiffness for > 1 hour everyday for 6 weeks
   –   Swelling of the wrists, MCPs, PIPs for 6 weeks
   –   Swelling of 3 joints for 6 weeks
   –   Symmetric joint swelling for 6 weeks
   –   Joint erosions on X-Ray
   –   RF positive
   –   Rheumatoid nodules

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2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria
• The American College of Rheumatology (ACR) and the European League
  Against Rheumatism (EULAR) establish a point value between 0 and 10.
• Every patient with a point total of 6 or higher is unequivocally classified
  as an RA patient
     – Provided S/he has synovitis in at least one joint and
     – That there is no other diagnosis better explaining the synovitis.

Four areas are covered in the diagnosis:
1. Joint involvement – depending on the type and number of joints: up
    to 5 points
2. Serological parameters – including the rheumatoid factors as well as
    ACPA (Anti- citrullinated protein antibody): up to 3 points depending
    on titre level
3. Duration of arthritis: 1 point for symptoms lasting six weeks or longer
4. Acute phase reactants: 1 point for elevated ESR, or elevated CRP
    value (c-reactive protein)

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Risk factors
      – Female
      – Genetic susceptibility
      – HLA DR4, DR1, DW15
      – Monozygotic twins
      – I⁰ relatives
      – SE positive alleles (HLA DR β₁)
      – Cigarette smoking

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          – RA is an autoimmune disease triggered by exposure
            of a genetically susceptible host
                       Autoimmune reaction

Activation of CD4 +T cells and       Produce        Produce by macrophages and
lymphocytes and the release of                      synovial lining cells that are
inflammatory mediators and cytokines                activated by the T – cells in the
                Synovial cells
Various mediators of inflammation (PG ) and
Matrix metalloproteinase (cartilage destruction)             Bone destruction

    9/16/2011                    Progressive joint damage
                                        Dr. Alka Stoelinga                              17
                           Synovium ( hyperplastic )

 Synovium rich in Inflammatory cells
 becomes adherent and grows over the
 articular surface , forming a Pannus

                                                          - an inflammatory exdudate
                                                          overlying the synovial cells on
                                                          the inside of a joint
            Release of IL-1 , platelet –
            derived growth factor

  Cause cartilage destruction and bone erosion

9/16/2011                            Dr. Alka Stoelinga                             18
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Clinical Features
1.    Slow and Insidious onset
      – Joint pain, Stiffness, Symmetrical swelling of peripheral joints
      – Initially pain on movement of joint- later – rest pain
      – Florid morning stiffness
      – Polyarthritis- First affecting the small joints of fingers and toes;
        followed by wrists, elbows, shoulders, knees, ankles, subtalar and
        midtarsal joints
      – Swelling of PIP joints Spindle shaped fingers
      – Swelling of MTP joints Broadening of forefoot
2.    Acute Onset
     –      Acute Polyarthritis with severe systemic symptoms
3.    Systemic Onset
     –      Mild fever
     –      Malaise
     –      Fatigue
     –      Weight loss
4.    Palindromic onset
     –      Recurrent acute episodes of joint pain and stiffness lasting for few
            hrs to days
9/16/2011                            Dr. Alka Stoelinga                            20
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Clinical Features

Damage to ligaments and tendons:
    – Radial deviation of wrists and Ulnar deviation of digits (due
      to rupture of the collateral ligaments at the MCP joints )
    – Swan-neck deformity ( due to rupture of the volar plate of
      the PIP joints ) and
    – Boutonniere deformity (due to rupture of central extensors)
      of the fingers
    – Z- deformity of thumbs
    – Forefoot- Clawing of toes

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 Clinical Features
1.   Systemic                  4. Lymphatic                   7.   Ocular
•    Fever                     • Splenomegaly                 •    Scleritis, Episcleritis
•    Malaise                   • Felty’s syndrome             •    Scleromalacia performs
•    Fatigue                                                  •    Keratoconjunctivitis
•    Weight loss                                                   sicca
2.   Musculoskeletal           5. Pulmonary                   8.   Vasculitis
•    Muscle wasting            • Pleurisy, Effusions          •    Digital Ischemia
•    Tenosynovitis; Bursitis   • Nodules in lungs and         •    Leg Ulcers
•    Osteoporosis                 Pleura                      •    Pyoderma gangrenosum
                               • Fibrosing alveolitis         •    Mesenteric ischemia
3.   Hematological             6. Cardiac                     9. Neurological
•    Anemia                    • Pericarditis, Myocarditis,   • Peripheral neuropathy
•    Thrombocytosis               Endocarditis                • Spinal cord compression
•    Eosinophilia              • Nodules in Pericardium          (Cervical)
•    Felty’s syndrome (RA+     • Pericardial Effusion         • Mononeuritic Multiplex
     Neutropenia+                                             • Carpal Tunnel Syndrome

10. Rheumatoid nodules                          11. Amyloidosis
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• Rheumatoid nodules
     – Initial event caused by vasculitis
     – Common Sites: Olecranon, Occiput, Achilles tendon
• Felty’s syndrome (RA+ Neutropenia+ Splenomegaly)
• Caplan syndrome (RA+ Pulmonary involvement)

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1.      X-rays of Hands and Feet
        – Early Stage: No change
        – Juxta-articular osteopenia, soft tissue swelling and loss of joint space
        – Advanced Stage: Bony erosions and subluxation
2.      High-frequency transducers - Can depict 20% more erosions than conventional
3.      Color Doppler and Power Doppler ultrasound- Show vascular signals of active synovitis
        depending on the degree of inflammation; are useful in assessing synovial
1. Immunological tests
        – Anti-citrullinated protein antibodies (ACPAs)- Anti-CCP/ Anti- MCV assays
        – Serological point-of-care test (POCT)
        – RF
2.      OTHER TESTS:
        – ANA, ESR, CRP : usually raised but may be normal.
        – CBC- Normochromic, Normocytic anemia and reactive thrombocytosis.
        – Ferritin levels- Raised ferritin but low serum iron concentration and total iron
          binding capacity.
        – LFT- mild elevation of alkaline phosphatase
        – Uric acid/synovial fluid analysis: excludes polyarticular gout.
        – Urinalysis: microscopic hematuria/proteinuria may suggest connective tissue
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–   Show soft tissue swelling,
–   periarticular osteopenia
–   loss of joint space
–   erosions
–   Deformity
–   Radial deviation of the wrist
–   Ulnar deviation of the fingers
–   Swan neck deformity ( flexon –
    hyperextension deformity ).

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• Based upon Clinical criteria
• 2010 ACR / EULAR Rheumatoid Arthritis
  Classification Criteria >/= 6
• Anti-CCP (Positive in 67% of RA cases; but are rarely
  positive if RA is not present-
• Specificity- 95%)
• Anti MCV
• POCT (RF+ Anti MCV) for early diagnosis of RA (72%
  Sensitive; 99.7% Specificity)

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The goal of treatment is:
• Alleviating the current symptoms
• Preventing the future destruction of the joints
  with the resulting handicap if the disease is
  left unchecked

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1.     Disease modifying anti-rheumatic drugs (DMARDs)
      –      reduces the rate of damage to bone and cartilage
      –      Methotrexate (MTX)
      –      Cyclosporine
      –      Sulfasalazine
      –      Azathioprine
      –      D-Penicillamine
      –      Hydroxychloroquine
2.     Combi-therapy of DMARDs
      –      Methotrexate – Hydroxychloroquine
      –      Methotrexate – sulfasalazine
      –      Sulfasalazine – Hydroxychloroquine
      –      Methotrexate – Hydroxychloroquine – sulfasalazine
3.     Anti-inflammatory agents and analgesics
      –      Glucocorticoids (Prednisolone, Methylprednisolone)
      –      NSAIDS (Acetaminophen, Ibuprofen, Naproxen, meloxicam, etodolac,
             nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac,
             diflusinal, indomethicin, Ketoprofen, Oxaprozin and piroxicam)

     9/16/2011                            Dr. Alka Stoelinga                               35
4. Surgery
  –      Synovectomy
  –      Osteotomy
  –      Arthrodesis
  –      Arthroplasties

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•   Average life span is reduced by 8-15 years
•   About 50%- 5 year survival rate with severe disease
•   50% disabled/ unable to work within 10 years
•   Poorer prognosis is associated with:
      –     Insidious onset
      –     Extra-articular manifestations
      –     Functional disability at 1 year after start of disease
      –     High RF titres
      –     HLA-DR4 present
      –     X-Ray evidence of erosions within 3 years

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