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John J. Cush, MD Chief, Rheumatology & Clinical Immunology Presbyterian Hospital of Dallas Clinical Professor of Internal Medicine UT Southwestern Medical School

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Title: John J. Cush, MD Chief, Rheumatology & Clinical Immunology Presbyterian Hospital of Dallas Clinical Professor of Internal Medicine UT Southwestern Medical School


1
John J. Cush, MDChief, Rheumatology Clinical
ImmunologyPresbyterian Hospital of
DallasClinical Professor of Internal MedicineUT
Southwestern Medical School
  • St. John's University, B.S. 1977
  • SGUSOM, MD July 1981
  • Internal Medicine Residency 81-84
  • Chief Medical Resident 83-84
  • Rheumatology Fellowship
  • Parkland Memorial Hospital, 84 - 87
  • ECFMG, 1980 FLEX (I-III), 1981
  • License GA, NY, TX 1989
  • Diplomate in Internal Medicine, 1984
  • Diplomate in Rheumatology, 1988
  • UTSWMC Faculty 87- present
  • Chairman, Int Medicine SGU, 2004-
  • Intern of the Year - Coney Island 1982
  • Chief Medical Resident 1984
  • Best Doctors In America 1996-2005
  • Teacher of the Year - PHD 1998-99
  • Best Doctors in Dallas 2002-05
  • Arthritis Foundation, Chairman, Prof, Educ
  • American College of Rheumatology
  • FDA Arthritis Advisory Committee 2002 -
  • St. Georges University School of Medicine
  • Chairman, Academic Board 1990 -
  • Trustee, Board of Trustee's 1993
  • 100 Publications
  • 2 Books

2
The TEST
  • Lectures Big picture gt stressed gt anything
    covered
  • Syllabus yes its dense with info. Look for
    overlap.
  • Lectures Syllabus synergistic importance
  • Common presentations, Common Disorders
  • Common presentations of Uncommon Disorders
  • Wont do Rare Presentations of Rare Disorders
  • Pathogenesis
  • Clinical manifestations Outcome
  • Basic Treatment Decisions
  • 6-8 Questions

3
Rheumatology Programme
  • Tuesday 4/12
  • !st Hr Evaluation of Rheumatic Patient
  • Laboratory testing rheumatic pts
  • 2nd Hr SLE
  • Osteoarthritis vs Rheumatoid arthritis
  • Wednesday AM
  • 3rd Hr Gout, Pseudogout,
  • Juvenile arthritis, Rheumatic Fever
  • 4th Hr Spondyloarthropathies AS, Reactive,
    Psoriatic, IBD
  • Wednesday PM
  • 5th Hr myositis, Scleroderma, Fibromyalgia,
    Carpal Tunnel
  • Thursday
  • 6th Hr Vasculitis
  • Infectious Arthritis, Lyme Disease
  • 7th Hr Anti-Rheumatic Drugs
  • Test questions/review

4
Rheumatology
  • Int. Medicine (3yrs) 2 yrs Rheumatology,
    fellowship
  • Specialize in
  • Musculoskeletal disorders Medical management,
    surgical indications coordinate adjunctive care
    (OT, PT, Vocational)
  • Autoimmune disorders
  • Clinical Immunologists
  • Clinical Pharmacologists rheumatologists
    specialize in immunosuppressive,
    immunomodulatory, cytotoxic therapies
  • Whats the average age in rheumatology clinic?
  • 70 million affected
  • Only 3,200 Board Certified Rheumatologists in USA
    (???)

5
Rheumatologic Assessments
  • What is needed to establish a differential
    diagnosis
  • Consider the most common conditions
  • Diagnosis by
  • Age, Sex, Race
  • Type of presentation Febrile, Acute, Chronic,
    Widespread pain
  • Number of Joints
  • LABS DO NOT MAKE A DIAGNOSIS HP DOES!
  • How can labs lead you astray?
  • ESR/CRP Origins and associations
  • Serologies (RF, ANA, CCP, APL, ANCA) when to do
  • in what OTHER diseases are they positive?
  • Arthrocentesis for diagnosis

6
Common Causes of Joint Pain
  • Musculoskeletal conditions gt 70 million
  • 315 million MD office visits (Disability 17
    million)
  • Low Back Pain gt 5 million per year
  • Trauma/Fracture
  • Osteoarthritis 12-20 million
  • Repetitive strain/injury
  • Bursitis,TendinitisCarpal tunnel syndrome 2.1
    million
  • Fibromyalgia 3.7 million
  • Rheumatoid Arthritis 2.1-2.5 million
  • Gout, Pseudogout 2 million
  • Spondyloarthropathy AS, PsA, Reactive, IBD
    arthritis (1.4 mil)
  • Polymyalgia rheumatica/temporal arteritis
  • Infectious arthritis

7
Uncommon Causes of Joint Pain
  • Systemic lupus erythematosus 239,000
  • Drug-induced lupus
  • Scleroderma / CREST lt 50,000
  • Mixed Connective Tissue Disease (MCTD)
  • Vasculitis (Polyarteritis nodosa, Wegeners
    granulomatosus)
  • Inflammatory myositis lt50,000
  • Juvenile arthritis
  • Behcets syndrome
  • Sarcoidosis
  • Relapsing polychrondritis
  • Stills Disease

8
Goals of Assessment
  • Identify Red Flag conditions
  • Conditions with sufficient morbidity/mortality to
    warrant an expedited diagnosis
  • Make a timely diagnosis
  • Common conditions occur commonly
  • Many MS conditions are self-limiting
  • Some conditions require serial evaluation over
    time to make a Dx
  • Provide relief, reassurance and plan for
    evaluation and treatment

9
RED FLAG CONDITIONS
  • FRACTURE
  • SEPTIC ARTHRITIS
  • GOUT/PSEUDOGOUT

10
Key Questions
  • Inflammatory vs. Noninflammatory ?
  • Acute vs. Chronic ? (lt or gt 6 weeks)
  • Articular vs. Periarticular ?
  • Mono/Oligoarthritis vs Polyarthritis ?
  • (Focal) (Widespread)
  • Are there RED FLAGS?

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Inflammatory vs Noninflammatory
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Articular vs. Periarticular
  • Finding ARTICULAR PERIARTICULAR
  • Pain Diffuse, deep "point" tenderness
  • ROM Pain Activepassive Active motion
  • in all planes in few planes
  • Swelling Common Uncommon

15
Mono/Oligo vs Polyarticular
  • Monarticular
  • Osteoarthritis
  • Fracture
  • Osteonecrosis
  • Gout or Pseudogout
  • Septic arthritis
  • Lyme disease
  • Reactive arthrtis
  • Tuberculous/Fungal arthritis
  • Sarcoidosis
  • Polyarticular
  • Osteoarthritis
  • Rheumatoid arthritis
  • Psoriatic arthritis
  • Viral arthritis
  • Serum Sickness
  • Juvenile arthritis
  • SLE/PSS/MCTD

16
Nonarticular Pain
  • Fibromyalgia
  • Fracture
  • Bursitis, Tendinitis, Enthesitis, Periostitis
  • Carpal tunnel syndrome
  • Polymyalgia rheumatica
  • Sickle Cell Crisis
  • Raynauds phenomenon
  • Reflex sympathetic dystrophy
  • Myxedema

17
Formulating a Differential Dx
18
Musculoskeletal Complaint
lt 55 yrs.
gt 55 yrs.
19
History Clues to Diagnosis
  • Age
  • Young JRA, SLE, Reiter's, GC arthritis
  • Middle Fibromyalgia, tendinitis, bursitis, LBP
    RA
  • Elderly OA, crystals, PMR, septic, osteoporosis
  • Sex
  • Males Gout, AS, Reiter's syndrome
  • Females Fibrositis, RA, SLE, osteoarthritis
  • Race
  • White PMR, GCA and Wegener's
  • Black SLE, sarcoidosis
  • Asian RA, SLE, Takayasu's arteritis, Behcet's

20
Onset Chronology
  • Acute Fracture, septic arthritis, gout,
    rheumatic fever, Reiter's syndrome
  • Chronic OA, RA, SLE, psoriatic arthritis,
    fibromyalgia
  • Intermittent gout, pseudogout, Lyme, Familial
    Mediterranean Fever
  • Additive OA, RA, psoriatic
  • Migratory Viral arthritis (hepatitis B),
    rheumatic fever, GC arthritis

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24
Drug Induced Syndromes
  • Myalgias/myopathy Steroids, lovastatin, statins,
    clofibrate, alcohol, cocaine
  • Gout Diuretics, ASA, cytotoxics, cyclosporine,
    alcohol, moonshine
  • Drug-induced lupus hydralazine, procainamide,
    quinidine, INH phenytoin, chlorpromazine, TCN,
    TNF inhibitors
  • Osteopenia Steroids, chronic heparin, phenytoin
  • Osteonecrosis Steroids, alcohol, radiation
    therapy

25
Rheumatic Review of Systems
  • Constitutional fever, wt loss, fatigue
  • Ocular blurred vision, diplopia, conjunctivitis,
    dry eyes
  • Oral dental caries, ulcers, dysphagia, dry mouth
  • GI hx ulcers, Abd pain, change in BM, melena,
    jaundice
  • Pulm SOB, DOE, hemoptysis, wheezing
  • CVS angina/CP, arrhythmia, HTN, Raynauds
  • Skin photosensitivity, alopecia, nails, rash
  • CNS HA, Sz, weakness, paraesthesias
  • Reproductive sexual dysfunction, promiscuity,
    genital lesions, miscarriages, impotence
  • MS joint pain/swelling, stiffness, ROM/function,
    nodules

26
Rheumatic Review of Systems
  • Fever/Constitutional septic arthritis,
    vasculitis, Stills disease
  • Ocular Reiters, Behcets, Sjogrens, Cataracts
    (steroids)
  • Oral Sjogrens, Lupus, GC, myositis, drugs
  • GI Reactive arthritis, IBD, hepatitis,
    Polyarteritis, Scleroderma
  • Pulm SLE, RA lung, Churg-Strauss, Wegeners,
    Scleroderma
  • CVS Vasculitis, PSS, Raynauds, antiphospholipid
    syndrome
  • Skin SLE, psoriatic, vasculitis, Kawasaki
    syndrome
  • CNS lupus carpal tunnel, antiphospholipid,
    vasculitis
  • GYN/GU antiphospholipid, SLE, Reiters, Behcets,
    CTX
  • Musculoskeletal Gout, RA, OA, fibromyalgia,
    fracture

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Musculoskeletal Exam
  • Observe patient function (walk, write, turn,
    rise, etc)
  • Identify articular vs. periarticular vs.
    extraarticular
  • Detailed recording of joint exam (eg, tender
    joints)
  • Specific maneuvers
  • Tinels sign? Median N.? Carpal Tunnel syndrome
  • Phalens sign ? Median N.? Carpal Tunnel syndrome
  • Bulge sign ? Syn.Fluid Suprapatellar pouch? Knee
    effusion
  • Drop arm sign ?Complete Rotator Cuff Tear?Trauma?
  • McMurray sign ?Torque on Meniscus ? Cartilage Tear

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RHEUMATOSCREEN PLUS
?
  • CBC differential
  • Chem-20
  • Uric acid
  • Urinalysis
  • ESR
  • C-reactive protein
  • RPR
  • CPK
  • Aldolase
  • ASO
  • Immune complexs
  • TFTs w/ TSH
  • IgM- RF
  • ANA
  • ENA (SSA, SSB, RNP, Sm)
  • dsDNA-Crithidia
  • Scl-70, Jo-1
  • Histone Abs
  • Ribosomal P Ab
  • Coombs
  • C3, C4
  • CH50
  • Cryoglobulins
  • Lupus anticoag.
  • Cardiolipin Ab
  • c-ANCA
  • anti-PR3, -MPO
  • anti-GBM
  • SPEP
  • Lyme titer
  • HIV
  • Chlamydia Ab.
  • Parvovirus B19
  • HBV, HCV, HAV
  • HLA typing

CUSHY LABS INC. YOUR INDECISION IS OUR BREAD AND
BUTTER
34
Kingstown General Hosp. CheapoScreen
?
CBC diff 35.00 Chem-20
108.00 Urinalysis 30.00 ESR or CRP
25.30 Uric acid 40.00
  • ANA
  • RF

238.30
CUSHY LABS INC. YOUR INDECISION IS OUR BREAD AND
BUTTER
35
Further Investigations
  • Many conditions are self-limiting
  • Consider when
  • Systemic manifestations (fever, wt.loss, rash,
    etc)
  • Trauma (do exam or imaging for Fracture, ligament
    tear)
  • Neurologic manifestations
  • Lack of response to observation symptomatic Rx
    (lt6wks)
  • Chronicity ( gt 6 weeks)

36
Common Rheumatic Tests
  • Tests Sensitivity Specificity
  • Rheumatoid 80 95
  • Factor
  • Antinuclear 98 93
  • Antibody
  • Uric Acid 63 96

37
Acute Phase Reactants
  • Erythrocyte Sedimentation Rate (nonspecific)
  • C-Reactive Protein (CRP)
  • Fibrinogen
  • Serum Amyloid A (SAA)
  • Ceruloplasmin
  • Complement (C3, C4)
  • Haptoglobin
  • Ferritin
  • Other indicators leukocytosis, thrombocytosis,
    hypoalbuminemia, anemia of chronic disease

38
Erythrocyte Sedimentation Rate
  • ESR Introduced by Fahraeus 1918
  • Mechanisms Rouleaux formation
  • Characteristics of RBCs
  • Shear forces and viscosity of plasma
  • Bridging forces of macromolecules. High MW
    fibrinogen tends to lessen the negative charge
    between RBCs and promotes aggregation.
  • Methods Westergren method
  • Low ESR Polycythemia, Sickle cell, hemolytic
    anemia, hemeglobinopathy, spherocytosis, delay,
    hypofibrinogen, hyperviscosity (Waldenstroms)
  • High ESR Anemia, hypercholesterolemia, female,
    pregnancy, inflammation, malignancy,nephrotic
    syndrome

39
ESR Age
MAge/2 FAge10/2
40
Extreme Elevation of ESRRME Fincher, Arch Int
Med 1461986
41
ACP Recommendations for Diagnostic Use of
Erythrocyte Sedimentation Rate
  • The ESR should not be used to screen
    asymptomatic persons for disease
  • The ESR should be used selectively and
    interpreted with caution....Extreme elevation of
    the ESR seldom occurs in patients with no
    evidence of serious disease
  • If there is no immediate explanation for an
    increased ESR, the physician should repeat the
    test in several months rather than search for
    occult disease
  • The ESR is indicated for the diagnosis and
    monitoring of temporal arteritis and polymyalgia
    rheumatica
  • In diagnosing and monitoring patients with
    rheumatoid arthritis, the ESR should be used
    prinicipally to resolve conflicting clinical
    evidence
  • The ESR may be helpful in monitoring patients
    with treated Hodgkins disease

42
Antinuclear Antibodies
  • 99.99 of SLE patients are ANA positive
  • () ANA is not diagnostic of SLE
  • 20 million Americans are ANA
  • 239,000 SLE patients in the USA
  • Normals 5 ANA Elderly 15 ANA
  • Significance rests w/ Clinical Hx, titer, pattern
  • Higher the titer, the greater the suspicion of SLE

43
  • ANA PATTERN Ag Identified Clinical Correlate
  • Diffuse DeoxyRNP Low titerNonspecific
  • Histones Drug-induced lupus
  • Peripheral ds-DNA 50 of SLE (specific)
  • Speckled U1-RNP gt90 of MCTD
  • Sm 30 of SLE (specific)
  • Ro (SS-A) Sjogrens 60, SCLE
  • Neonatal LE, ANA(-)LE
  • La (SS-B) 50 Sjogrens, 15 SLE
  • Scl-70 40 of PSS (diffuse dz)
  • PM-1 PM/DM
  • Jo-1 PM, Lung Dz, Arthritis
  • Nucleolar RNA Polymerase I, others 40 of
    PSS
  • Centromere Kinetochore 75 CREST (limited dz)
  • Cytoplasmic Ro, ribosomal P SS, SLE psychosis

44
Antinuclear Antibodies
  • Virtually present in all SLE patients
  • Not synonymous with a Dx of SLE
  • May be present in other conditions
  • Drug-induced (procainamide, hydralazine,
    quinidine, TCN, TNF inhib.)
  • Age (3X increase gt 65 yrs.)
  • Autoimmune disease
  • AIHA, Graves, Thyroiditis, RA, PM/DM,
    Scleroderma, Antiphospholipid syndrome
  • Chronic Renal or Hepatic disease
  • Neoplasia associated
  • Ineffective screen for arthritis or lupus
  • Specificity enhanced when ordered wisely

45
ANA and Odds of SLE
46
Frequency in SLE
  • Autoantibody Frequency
  • dsDNA 30-70
  • Sm 20-40
  • RNP 40-60
  • Ro 10-15
  • Ribosomal P 5-10
  • Histones 30
  • ACA 40-50

Egner W, J Clin Pathol 53424, 2000
47
Antiphospholipid Syndrome
  • Triad Any TEST plus
  • Thrombotic events
  • Spontaneous abortion(s)
  • Thrombocytopenia
  • Others Migraine, Raynauds, Libman-Sacks
    endocarditis, MR, Transverse myelitis, neuropathy
  • Ab found in gt30 SLE, other CTD
  • Correlates with IgG Ab and B2 Glycoprotein I
  • Rx Warfarin, heparin

PTT/LAC
RPR
Cardiolipin
3 Tests
48
Rheumatoid Factor
49
Rheumatoid Factor
  • 80 of RA patients. High titers associated with
    greater disease severity and extraarticular
    disease (NODULES).
  • Utility varies with use
  • Pre-test probability 1 Pos. Predictive Value
    7
  • Pre-test probability 50 Pos. Predictive Value
    88
  • Nonrheumatic causes
  • Age
  • Infection SBE 40, hepatitis 25, MTbc 8,
    syphilis 10, parasitic diseases gt50 (Chagas,
    leishmaniasis, schistosomiasis), leprosy 35,
    viral infection lt50 (rubella, mumps,
    influenza-15-65)
  • Pulmonary Dz Sarcoid lt30, IPF lt50, Silicosis
    40, Asbestosis 30
  • Malignancy 20
  • Primary Biliary Cirrhosis 50-75
  • 20 of RA patients are seronegative for RF

50
Age and Serologic Testing
51
Anti- Citrullinated Cyclic Peptides (CCP)
  • RF only in 20-50 of Early RA patients
  • Antibodies against Filaggrin (AFA), Keratin
    (AKA), anti-Perinuclear Factor (APF) directed
    against skin Ag profilaggrin - shown to be
    specific for RA, not popular, difficult to assay
  • Citrulline enzymatically post-translationally
    modified arginine
  • CCP a peptide variant of citrulline-rich
    filaggrin epitopes
  • CCP Abs thought to represent AKA, APF,
    anti-fillagrin Abs
  • As Sensitive as RF (40-66)
  • Very Specific for RA (Specificity 98)
  • Correlates with
  • Early RA, aggressive Dz,
  • ? risk of Xray damage, shared epitopes
  • Patients w/ Shared Epitope have enhanced response
    to citrulline self-peptides ? CCP may contribute
    to RA pathogenesis

52
CCP antibodies by ELISA
AITD autoimmune thyroid dz MGUS-monoclonal
gammopathy NC-normals
53
ANCA Anti-Neutrophil Cytoplasmic
Antibodies
  • C-ANCA, P-ANCA, myeloperoxidase (MPO),
    proteinase-3 (PR3)
  • ANCA antibodies that bind to enzymes present in
    the cytoplasm of neutrophils. Associated with
    several types of vasculitis.
  • C-ANCA cytoplasmic staining. 50 to 90
    sensitivity for Wegener's
  • P-ANCA exhibits perinuclear staining. Less
    specific, 60 of patients with microscopic
    polyarteritis and Churg-Straus syndrome.

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Serum Uric Acid Incidence of Gout
56
HLA-B27
  • Class I MHC Ag, associated with the
    spondyloarthropathies
  • Ankylosing spondylitis, Reiter's syndrome,
    Psoriatic arthritis, and enteropathic arthritis.
  • HLA-27 is found in up to 8 of normals
  • 3-4 of African-Americans, 1 of Orientals.
  • Increased risk of spondylitis and uveitis.
  • Indications may be used infrequently as a
    diagnostic test in AS, Reiters, Psoriatic
    arthritis

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Indications for Arthrocentesis
  • Monarthritis (acute or chronic)
  • Suspected infection or crystal-induced arthritis
  • New monarthritis in old polyarthritis
  • Joint effusion and trauma
  • Intrarticular therapy or Arthrography
  • Uncertain diagnosis

61
Synovial Fluid Analysis
  • Visual inspection (color, clarity, hemorrhagic)
  • Viscosity
  • - incr w/ normal (noninflam) SF (long string
    sign)
  • - decreased with inflammatory SF (loss of string
    sign)
  • Place in tubes EDTA (purple)-cell count.
    Na
    heparin (green)-Crystals
  • Cell Count and Differential
  • noninflammatory WBC lt 2000/mm3 (PMNs lt 75)
  • inflammatory WBC 2000 - 75,000/mm3 (PMNs gt
    75)
  • septic WBC gt 60,000/mm3 (PMNs gt80)
  • GC may have WBC from 30K - 75K

62
Synovial Fluid Analysis
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