RHEUMATOID ARTHRITIS for the internist...

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RHEUMATOID ARTHRITISfor the internist...

• Christopher Parker
• CPT (P), MC, USA
• Rheumatology Service
• WRAMC

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Introduction

• Interactive format
• Clinical features
• Laboratory features
• Extra-articular features
• Management considerations and paradigms
• Prognosis

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Case
Presentation 55 YOF complains of months of
bilateral hand pain. She describes progressive
morning stiffness lasting 3 hours with wrist,
MCP, and PIP pain and swelling. She has also
noted some discomfort and perhaps swelling in
her wrists, shoulders, knees, and toes. Review
of systems is unremarkable. What historical
features speak for RA?
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Rheumatoid nodule
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Rheumatoid Arthritis
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Case Presentation

• Physical exam is notable for swelling,
  tenderness, and warmth in the elbows, wrists,
  MCPs, PIPs, knees, and MTPs with non-tender soft
  tissue nodules over the olecronon.
• What is the difference between arthritis and
  arthralgia?
• Are there further tests that can be done to
  confirm the diagnosis?

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RA Erosion Progression
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Laboratory Exam

• WBC 5.2
• H/H 10/30 with normal RDW
• PLT 475k
• ESR 75
• RF 450
• ANA positive

• TSH normal
• CK normal
• P1-3 uric acid normal
• U/A normal

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Work-up of an inflammatory arthritis

• CBC, BUN/Cr, calcium, LFTs, uric acid, UA, HIV,
  RF, ANA, CPK, CXR
• further serologic evaluation and specific tests
  geared toward the presentation and results from
  above tests
• radiographs have a higher yield with chronic
  symptoms ( 6 weeks)

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Laboratory abnormalities

• anemia of chronic disease
• thrombocytosis in active disease
• low white cell count in Feltys
• ESR
• CRP

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Rheumatoid factor

• series of antibodies that recognize the Fc
  portion of an IgG molecule
• any serotype
• most IgM
• many conditions associated with RF positivity -
  chronic inflammation
• 70 RA positive at onset, overall 85 in first
  two years
• associated with more severe disease,
  extra-articular manifestations, mortality

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DDX of a positive RF

• normal - 1-4, 10-25 over age 70
• systemic autoimmune diseases
• infections
• malignancy
• chronic liver disease
• pulmonary diseases

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ANA in RA

• 25 RA are positive for ANA
• other serologies usually negative
• ? more severe disease (RA) with worse prognosis

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RA - Definition

• chronic systemic inflammatory disorder
• unknown etiology
• diarthroidal joints
• synovium affected
• bone, cartilage, ligaments
• deformity
• extra-articular manifestations

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RA - Definition

• clinical diagnosis
• symmetric polyarthritis of small joints
• subacute
• acute
• rheumatoid factor positivity
• erosive disease

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RA - Epidemiology

• worldwide distribution
• all races
• female male 31
• 1 adults in U.S.
• genetic associations
• HLA-DR4, DR1

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Case Study

• 29F presents with 3 weeks of pain and swelling in
  the wrists, MCPs, and PIPs. She has 2 hours of
  morning stiffness. She also complains of extreme
  fatigue and having difficulty keeping up with her
  four year old boy. Her son is well but had a
  rash a few weeks ago. Her exam confirms
  symmetric polyarticular inflammatory arthritis.
• Could she have something other than RA?

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Parvo Arthritis
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RA - differential diagnosis

• Common diseases
• spondyloarthropathies
• CTDs
• polyarticular gout
• CPPD
• viral infections
• fibromyalgia

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RA - differential diagnosis

• Uncommon
• hypothyroidism
• SBE
• hemochromatosis
• hypertrophic pulmonary osteoarthropathy
• hyperlipoproteinemias
• hemoglobinopathies
• relapsing polychondritis

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RA - differential diagnosis

• Uncommon
• rheumatic fever
• sarcoidosis
• lyme disease
• amyloid
• HIV
• malignancies/paraneoplastic syndromes

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RA - differential diagnosis

• Rare
• familial mediterranean fever
• multicentric reticulohistiocytosis
• whipples disease
• angioimmunoblastic lymphadenopathy

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Case Study

• 60WM with RA presents with progressive worsening
  of his joint complaints over the last few months
  with intermittant fever, swelling of his
  glands, and painful lesions on his finger tips.
  ROS notable for 5lb wt loss. Exam confirms
  polyarthritis and small digital infarctions.
• Could all of his symptoms be explained by RA?

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Extra-articular manifestations

• General
• fever, lymphadenopathy, weight loss, fatigue
• Dermatologic
• palmar erythema, nodules, vasculitis
• Ocular
• episcleritis/scleritis, scleromalacia perforans,
  choroid and retinal nodules

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Extra-articular manifestations

• Cardiac
• pericarditis, myocarditis, coronary vasculitis,
  nodules on valves
• Neuromuscular
• entrapment neuropathy, peripheral neuropathy,
  mononeuritis multiplex
• Hematologic
• Feltys syndrome, large granular lymphocyte
  syndrome, lymphomas

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Extra-articular manifestations

• Pulmonary
• pleuritis, nodules, interstitial lung disease,
  bronchiolitis obliterans, arteritis, effusions
• Others
• Sjogrens syndrome, amyloidosis

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Feltys syndrome

• classic triad
• RA, splenomegaly, leukopenia
• generally a neutropenia (
• thrombocytopenia may occur
• complications
• infections, non-healing leg ulcers
• most require no additional treatment for
  cytopenias
• splenectomy?

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Case Study

• You are tasked to back fill for a small army
  community hospital as a primary care provider
• GYN exam for perimenopausal 45WF
• MSK exam
• On NSAIDs
• No complaints of pain
• Are NSAIDs enough?
• What other medications could you use?

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RA - Management

• Nonpharmacologic
• rest
• fatigue, splinting
• pain relief
• heat, cold, ultrasound, paraffin, massage
• physical therapy
• occupational therapy
• Patient education

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RA - Management

• Pharmacologic
• analgesics
• NSAIDs - full dose
• corticosteroids
• prednisone at low dose - bridge, burst
• intra-articular steroids

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Disease modifying agents

• every patient should be considered for at least
  one modifying agent
• limitations
• may not prevent damage
• may not have lasting effect
• may not be tolerated due to toxicity

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DMARDs

• hydroxychloroquine
• mild non-erosive disease
• combinations
• 200 mg bid
• eye exams

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DMARDs

• Sulfasalazine
• 1 gm bid - tid
• CBC, LFTs
• onset 1 - 2 months
• Methotrexate
• most commonly used drug
• fast acting (4-6 weeks)
• po, SQ - weekly
• CBC, LFTs

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DMARDs

• IM Gold
• slow onset (3-6 months)
• weekly then monthly injections
• CBC, UA before each injection
• Oral Gold
• less effective
• slow acting (4-6 months)
• daily
• CBC, UA

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DMARDs

• Azathioprine
• 100-200 mg daily
• CBC, LFTs
• ?malignancy potential
• onset 2 - 3 months
• D-Penicillamine
• daily
• slow onset (3-6 months)
• CBC, UA
• autoimmune phenomenon

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DMARDs

• Cyclosporin A
• daily
• BP, UA
• Cyclophosphamide
• refractory cases
• CBC
• Chlorambucil
• CBC

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New Therapies for RA

• Enbrel
• Soluble tumor necrosis factor fusion protein
• Arava
• Leflunomide

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Chimeric A2 (cA2) Monoclonal Antibody
Mouse (binding site for TNF-a)
Human (IgG1)

• Chimeric (mouse/human) IgG1monoclonal antibody
• Binds to TNF-a with highaffinity and specificity

Knight, et al. Mol Immunol. 1993.
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DMARDs

• over the counter remedies
• report use of vitamins, health aids, unusual
  diets
• natural does not mean safe

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Case Study Follow Up

• During your training you became comfortable with
  the use of prednisone HCQ and begin treatment
  including prophylatic therapy for OP with
  calcium, vitamin D, and discuss ERT. You
  recommend follow up appointment in 4-8 weeks.
• What objective parameters will you use to
  determine if your therapy is effective?

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Response to therapy

• AM stiffness, total number swollen, tender
  joints, (S1T2W)
• perception of pain
• perception of overall response
• health assessment measurement
• ESR, CRP levels
• physicians assessment

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Criteria for Remission (ACR)

• no fatigue
• morning stiffness for 15 minutes or less
• no joint pain
• no joint tenderness or pain on motion
• no soft tissue swelling in joints or tendon
  sheath
• ESR
• 5 of 6 present for 2 months
• no vasculitis, pericarditis, pleuritis, myositis,
  weight loss, fever

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RA - long term prognosis

• RA shortens survival and produces disability
• 1/3 leave work force in five years
• aggressive DMARD TX can reduce disability by 30
  in 10-20 years

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