Transcript ppt
John J. Cush, MD Chief, Rheumatology & Clinical Immunology Presbyterian Hospital of Dallas Clinical Professor of Internal Medicine UT 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 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 Rheumatology Programme Tuesday 4/12 Wednesday AM 3rd Hr: Gout, Pseudogout, • Juvenile arthritis, Rheumatic Fever 4th Hr: Spondyloarthropathies: AS, Reactive, Psoriatic, IBD Wednesday PM !st Hr: Evaluation of Rheumatic Patient • Laboratory testing rheumatic pts 2nd Hr: SLE • Osteoarthritis vs Rheumatoid arthritis 5th Hr: myositis, Scleroderma, Fibromyalgia, Carpal Tunnel Thursday 6th Hr: Vasculitis • Infectious Arthritis, Lyme Disease 7th Hr: Anti-Rheumatic Drugs • Test questions/review 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 () Rheumatologic Assessments What is needed to establish a differential diagnosis Consider the most common conditions Diagnosis by: 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 Age, Sex, Race Type of presentation: Febrile, Acute, Chronic, Widespread pain Number of Joints in what OTHER diseases are they positive? Arthrocentesis for diagnosis 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 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 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 RED FLAG CONDITIONS FRACTURE SEPTIC ARTHRITIS GOUT/PSEUDOGOUT Key Questions Inflammatory vs. Noninflammatory ? Acute vs. Chronic ? (< or > 6 weeks) Articular vs. Periarticular ? Mono/Oligoarthritis vs Polyarthritis ? (Focal) (Widespread) Are there RED FLAGS? Inflammatory vs Noninflammatory Feature Inflammatory Noninflammatory Pain (worse when?) Yes (morning) Yes (night) Swelling Soft Tissue (+ effusion) Bony Erythema Sometimes Present Absent Warmth Sometimes Present Absent Morning Stiffness Prominent ( > 1 hr.) Minor ( < 45 min.) Systemic Features+ Sometimes Present Absent Elevated ESR or CRP* Frequent Uncommon Synovial Fluid WBC WBC > 2,000 /mm3 WBC < 2,000 /mm3 Examples Septic arthritis, RA, Gout, Polymyalgia rheumatica Osteoarthritis, Adhesive Capsulitis,Osteonecrosis + fever, rash, weight loss, anorexia, anemia * ESR: erythrocyte sedimentation rate; CRP: C-reactive protein Articular vs. Periarticular Finding ARTICULAR PERIARTICULAR Pain Diffuse, deep "point" tenderness Active+passive in all planes Active motion in few planes Common Uncommon ROM Pain Swelling 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 Nonarticular Pain Fibromyalgia Fracture Bursitis, Tendinitis, Enthesitis, Periostitis Carpal tunnel syndrome Polymyalgia rheumatica Sickle Cell Crisis Raynaud’s phenomenon Reflex sympathetic dystrophy Myxedema Formulating a Differential Dx Inflammatory Noninflammatory Articular Nonarticular Septic Gout Rheumatoid arthritis Psoriatic arthritis Osteoarthritis Charcot Joint Fracture Bursitis Enthesitis PMR Polymyositis Fibromyalgia Carpal tunnel RSD Musculoskeletal Complaint Trauma Fracture Low Back Pain? Orthopedic Evaluation Fibromyalgia < 55 yrs. > 55 yrs. Repetitive Strain Injury (carpal tunnel,bursitis) Osteoarthritis Gout (males only) Gout Pseudogout Rheumatoid Arthritis Polymyalgia Rheumatica Psoriatic Reiters IBD Arthritis Osteoporotic Fracture Infectious Arthritis (GC, Viral, Bacterial, Lyme) Septic Arthritis (Bacterial) 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 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 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 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 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 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 TearTrauma? McMurray sign Torque on Meniscus Cartilage Tear Right Joint TMJ SC AC Shoulder Elbow Wrist CMC1 MCP 1-5 PIP 1-5 Hip Knee Ankle Tarsus MTP 1-5 Toe 1-5 Left RHEUMATOSCREEN PLUS CBC & differential IgM- RF Lupus anticoag. Chem-20 ANA Cardiolipin Ab Uric acid ENA (SSA, SSB, c-ANCA Urinalysis ESR C-reactive protein RPR CPK Aldolase ASO Immune complexs TFT’s w/ TSH RNP, Sm) dsDNA-Crithidia Scl-70, Jo-1 Histone Abs Ribosomal P Ab Coombs C3, C4 CH50 Cryoglobulins 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” Kingstown General Hosp. CheapoScreen CBC & diff Chem-20 Urinalysis ESR or CRP Uric acid $35.00 $108.00 $30.00 $25.30 $40.00 ANA + RF $ 238.30 CUSHY LABS INC. “YOUR INDECISION IS OUR BREAD AND BUTTER” 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) Common Rheumatic Tests Tests Rheumatoid Factor Antinuclear Antibody Uric Acid Sensitivity Specificity 80% 95% 98% 93% 63% 96% 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 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 ESR & Age 60 ESR mm/hr 50 40 30 20 10 0 <30 30-39 40-49 50-59 60-69 70-79 80-89 Age (years) M=Age/2 F=Age+10/2 Extreme Elevation of ESR RME Fincher, Arch Int Med 146:1986 Cause ESR > 100 (%) ESR 75 –99 (%) Infection 14 (33) 6 (16) Renal Dz 7 (17) 4 (11) Neoplasm 7 (17) 4 (11) Inflammatory 6 (14) 6 (16) Miscellaneous 4 (9.5) 0 Unknown 4 (9.5) 17 (46) 42 (100) 37 (100) Total 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 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 ANA PATTERN Ag Identified Clinical Correlate Diffuse DeoxyRNP Histones Low titer=Nonspecific Drug-induced lupus Peripheral ds-DNA 50% of SLE (specific) Speckled U1-RNP Sm Ro (SS-A) >90% of MCTD 30% of SLE (specific) Sjogrens 60%, SCLE Neonatal LE, ANA(-)LE 50% Sjogrens, 15% SLE 40% of PSS (diffuse dz) PM/DM PM, Lung Dz, Arthritis La (SS-B) Scl-70 PM-1 Jo-1 Nucleolar RNA Polymerase I, others Centromere Cytoplasmic (nonspecific) Kinetochore Ro, ribosomal P Cardiolipin AMA, ASMA 40% of PSS 75% CREST (limited dz) SS, SLE psychosis Thrombosis,Sp. Abort, Plts PBC, Chr. active hepatitis 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 Percent ANA+ and Odds of SLE 100 90 80 70 60 50 40 30 20 10 0 1 2 3 criteria 4 +ANA 5 6 Frequency in SLE Autoantibody dsDNA Sm RNP Ro Ribosomal P Histones ACA Frequency 30-70% 20-40% 40-60% 10-15% 5-10% 30% 40-50% Egner W, J Clin Pathol 53:424, 2000 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 Rheumatoid Factor 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% Pre-test probability = 50% Pos. Predictive Value =7% 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 Age and Serologic Testing ANA RF 16 14 percent (+) 12 10 8 6 4 2 0 20-30 yrs > 65 yrs Anti- Citrullinated Cyclic Peptides (CCP) RF+ only in 20-50% of Early RA patients Antibodies against Filaggrin (AFA), Keratin (AKA), antiPerinuclear 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 selfpeptides CCP may contribute to RA pathogenesis CCP antibodies by ELISA AITD: autoimmune thyroid dz; MGUS-monoclonal gammopathy; NC-normals 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. Serum Uric Acid & Incidence of Gout Serum Urate mg/dl Gout 5 year Incidence/yr/1000 cummulative < 7.0 0.8 5 7.0 – 7.9 0.9 6 8.0 – 8.9 4.1 9.8 > 9.0 49 220 HLA-B27 Class I MHC Ag, associated with the spondyloarthropathies HLA-27 is found in up to 8% of normals Ankylosing spondylitis, Reiter's syndrome, Psoriatic arthritis, and enteropathic arthritis. 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 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 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 < 2000/mm3 (PMNs < 75%) inflammatory: WBC = 2000 - 75,000/mm3 (PMNs > 75%) septic: WBC > 60,000/mm3 (PMNs >80%) • GC may have WBC from 30K - 75K Synovial Fluid Analysis Noninflammatory Type I Inflammatory Type II Septic Type III Hemorrhagic Type IV Amber-yellow Yellow Purulent Bloody Clear Cloudy Opaque Opaque Viscosity High (+ String sign) Decreased (- string) Decreased ( - string) Variable Cell Count (%PMN) 200-2000 (< 25% PMN) 2000-75,000 ( > 50% PMN) > 60,000 ( >80% PMN) RBC >> wbc Examples OA Trauma Osteonecrosis SLE RA Reiters, gout SLE Tbc, fungal Bacterial Gout Trauma Fracture Ligament tear Charcot Jt. PVS Appearance Clarity