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St. John's University, B.S. 1977 SGUSOM, MD July 1981 Internal Medicine Residency 81-84

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

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St. John's University, B.S. 1977 SGUSOM, MD July 1981 Internal Medicine Residency 81-84

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  1. 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 John J. Cush, MDChief, Rheumatology & Clinical ImmunologyPresbyterian Hospital of DallasClinical Professor of Internal MedicineUT Southwestern Medical School

  2. The TEST • Lectures: Big picture > stressed > 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; H&P 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 > 70 million • 315 million MD office visits (Disability 17 million) • Low Back Pain > 5 million per year • Trauma/Fracture • Osteoarthritis 12-20 million • Repetitive strain/injury • Bursitis,Tendinitis;Carpal 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 < 50,000 Mixed Connective Tissue Disease (MCTD) Vasculitis (Polyarteritis nodosa, Wegeners granulomatosus) Inflammatory myositis <50,000 Juvenile arthritis Behcets syndrome Sarcoidosis Relapsing polychrondritis Still’s 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 ? (< or > 6 weeks) • Articular vs. Periarticular ? • Mono/Oligoarthritis vs Polyarthritis ? (Focal) (Widespread) • Are there RED FLAGS?

  11. Inflammatory vs Noninflammatory

  12. Articular vs. Periarticular Finding ARTICULAR PERIARTICULAR Pain Diffuse, deep "point" tenderness ROM Pain Active+passive Active motion in all planes in few planes Swelling Common Uncommon

  13. 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 Mono/Oligo vs Polyarticular

  14. Nonarticular Pain • Fibromyalgia • Fracture • Bursitis, Tendinitis, Enthesitis, Periostitis • Carpal tunnel syndrome • Polymyalgia rheumatica • Sickle Cell Crisis • Raynaud’s phenomenon • Reflex sympathetic dystrophy • Myxedema

  15. Formulating a Differential Dx

  16. Musculoskeletal Complaint < 55 yrs. > 55 yrs.

  17. 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

  18. 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

  19. 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

  20. 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

  21. Rheumatic Review of Systems • Fever/Constitutional: septic arthritis, vasculitis, Still’s 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

  22. 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

  23. RHEUMATOSCREEN PLUS • 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 • CBC & differential • Chem-20 • Uric acid • Urinalysis • ESR • C-reactive protein • RPR • CPK • Aldolase • ASO • Immune complexs • TFT’s w/ TSH CUSHY LABS INC. “YOUR INDECISION IS OUR BREAD AND BUTTER”

  24. 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”

  25. 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 (<6wks) • Chronicity ( > 6 weeks)

  26. Common Rheumatic Tests Tests Sensitivity Specificity Rheumatoid 80% 95% Factor Antinuclear 98% 93% Antibody Uric Acid 63% 96%

  27. 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

  28. 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

  29. ESR & Age M=Age/2 F=Age+10/2

  30. Extreme Elevation of ESRRME Fincher, Arch Int Med 146:1986

  31. 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 Hodgkin’s disease

  32. 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

  33. ANA PATTERN Ag Identified Clinical Correlate Diffuse DeoxyRNP Low titer=Nonspecific Histones Drug-induced lupus Peripheral ds-DNA 50% of SLE (specific) Speckled U1-RNP >90% 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 (nonspecific) Cardiolipin Thrombosis,Sp. Abort, Plts AMA, ASMA PBC, Chr. active hepatitis

  34. 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 > 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

  35. ANA+ and Odds of SLE

  36. 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 53:424, 2000

  37. 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 >30% SLE, other CTD • Correlates with IgG Ab and B2 Glycoprotein I • Rx: Warfarin, heparin PTT/LAC RPR Cardiolipin 3 Tests

  38. Rheumatoid Factor

  39. 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 >50% (Chaga’s, leishmaniasis, schistosomiasis), leprosy 35%, viral infection <50% (rubella, mumps, influenza-15-65%) • Pulmonary Dz: Sarcoid <30%, IPF <50%, Silicosis 40%, Asbestosis 30% • Malignancy 20% • Primary Biliary Cirrhosis 50-75% • 20% of RA patients are seronegative for RF

  40. Age and Serologic Testing

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