Scott Vogelgesang, MD Division of Rheumatology/Immunology University of Iowa
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1 Scott Vogelgesang, MD Division of Rheumatology/Immunology University of Iowa
2 Basic Concepts ANA DsDNA Sm RNP SSA SSB RF/CCP ESR/CRP ANCA Cases Summary
3 Rheumatology Tests Lie and Mislead! Rheumatology Rally Pack (ANA, RF, ESR, Uric Acid) usually one positive result usually does not yield the diagnosis! Labs support good clinical impression Patient with polyarticular arthritis positive RF makes RA more likely. Patient with a rash and nonspecific joint pain negative ANA makes SLE very unlikely
4 93% of SLE patients (5-30% general population) Indirect Immunofluorescence Most common method Titers (< 1:40, 1:80, 1:640, > 1:640) Titers do not change with disease activity! Patterns Elisa No titers/patterns Results in Elisa units Lower sensitivity (higher false negatives) Who? Follow?
5 Sm ( Smith not smooth muscle ) - SLE High specificity (> 90%) Low sensitivity (~ 30%) RNP Seen in SLE (MCTD) DsDNA SLE High Specificity (> 90%) Low Sensitivity (~ 60%) SSA = Ro Sjogren s Syndrome SLE Neonatal SLE SSB = La Sjogren s Syndrome SLE Neonatal SLE
6 +RF (+CCP) RA 80% of pts with RA have +RF and/or CCP (when measured one year after onset) CCP More Specific and seen earlier in disease Predict destructive joint disease +RF in other diseases SLE Sjögren's Syndrome Chronic inflammatory diseases 5-15% of normal, healthy people * CCP (Cyclic Citrullinated Peptide): the new improved RF
7 ANA is positive in what percentage of patients with SLE (when measured on Hep-2 cells)? A. 27% B. 54% C. 73% D. 93% E. None of the above
8 ANA is positive in what percentage of patients with SLE (when measured on Hep-2 cells)? A. 27% B. 54% C. 73% D. 93% E. None of the above
9 25 yo woman has painful, swollen hands x 3 weeks; Difficulty opening jars, fine hand movts; AM stiffness x 45 min; ibuprofen 600 mg TID helps some; ROS: (-) Oral ulcers, chest pain, shortness of breath, rash, GERD, photosensitivity, dry eyes/mouth; FSHx: 5 th Grade Teacher; ETOH (-); Tob (-) PE: Vitals NL; 2+ swelling/pain all MCP/PIP Labs: CBC w NC/NC anemia; Chemistries NL; UA NL;ESR 35 Check ANA? RF? CCP? Diagnosis? Therapy?
10 Prednisone 10 mg/day 95% better RF 17 IU; CCP (-) Parvovirus IgM (+) Diagnosis?
11 ANA can be found in up to what % of patients in the general population? A. 5% B. 15% C. 30% D. 50% E. 75%
12 ANA can be found in up to what % of patients in the general population? A. 5% B. 15% C. 30% D. 50% E. 75%
13 Nonspecificmarker of inflammation Values increase with age Males: ULN: age/2 Females: [age + 10]/2) Can be independent of inflammation Elevations in the absence of inflammation Pregnancy Obesity (especially females) Hypergammaglobulinemia Age Anemia
14 Another acute phase reactant rises quickly after inflammatory stimulus falls quickly after inflammation stops Useful when ESR is normal or equivocal May reflect disease activity better than ESR
15 Renal Cirrhosis Pancreatitis Solid Tumors Mets Myeloma Lymphoma RA? PMR/GCA SLE? Vasculitis No Diagnosis 8% Other 11% Cancer 15% Autoimmune Disease 19% Infection 44% Pulmonary Urinary Tract Osteomyelitis
16 73 yo woman has shoulder pain for 3 months and getting worse; no precipitating event; can t sleep; hates to move her shoulders difficult to dress; AM stiffness x 1 hour ROS: (-) fever, chest pain, shortness of breath,headache, jaw pain, scalp tenderness, changes in vision, swollen joints FSHx: Family Hx (-); ETOH (-); Tob (-) Meds: ASA PE: Vitals normal; Uncomfortable in chair; Very limited bilateral shoulder ROM; rest (-); Labs: CBC with NC/NC anemia; Chemistry NL; ESR 17 What next? What is her Dx?
17 Presumed PMR (no GCA) < 5% have NL ESR Prednisone 15 mg/day started with 100% resolution within 12 hours Oh yeah, her CRP returned 2.3 mg/dl
18 Name at least 2 laboratory tests with high specificity for rheumatologic diseases and their disease associations. DsDNA: SLE Anti Sm: SLE C ANCA (Pr3): Wegener s CCP: RA?
19 C ANCA (cytoplasmic) P ANCA (perinuclear) Atypical P ANCA (UC ANCA)
20 C-ANCA: Wegener s Gran. (GPA) Pulmonary-Renal 95% sensitivity 95% specificity Proteinase 3 Pr-3 C-ANCA C is the 3rd letter of the alphabet: P-ANCA Microscopic polyangiitis NOT PAN) Myeloperoxidase UC-ANCA Ulcerative Colitis
21 27 yo woman complains of pain/stiffness in joints and muscles; Morning stiffness lasts 2 hours; Swelling of her hands; ibuprofen 800 TID without benefit; She has been reading on the internet and believes she has lupus. She shared her concern with the doctor at her office who ordered an ANA which returned positive at 1:80 speckled ROS: (+) oral ulcers, joint pain, fatigue, chest pain that worsens with coughing or deep breathing, photophobia; rest (-) FSHx:Family history (-); ETOH (-); Tob (-); Works as a secretary in a dermatologist s office Meds: OCP PE:Vitals normal. Anxious-appearing; no joint swelling with full ROM; rest (-) Labs: CBC, Chemistry Panel, UA NL Skip Ahead
22 S erositis O ral Ulcers A rthritis P hotosensitivity B lood R enal A NA I mmunologic testing N europsychiatric M alar Rash D iscoid Rash
23 27 yo woman complains of pain/stiffness in joints and muscles; Morning stiffness lasts 2 hours; Swelling of her hands; ibuprofen 800 TID without benefit; She has been reading on the internet and believes she has lupus. She shared her concern with the doctor at her office who ordered an ANA which returned positive at 1:80 speckled ROS: (+) oral ulcers, joint pain, fatigue, chest pain that worsens with coughing or deep breathing, photophobia; rest (-) FSHx:Family history (-); ETOH (-); Tob (-); Works as a secretary in a dermatologist s office Meds: OCP PE:Vitals normal. Anxious-appearing; no joint swelling with full ROM; rest (-)
24 27 yo woman complains of pain/stiffness in joints and muscles; Morning stiffness lasts 2 hours; Swelling of her hands; ibuprofen 800 TID without benefit; She has been reading on the internet and believes she has lupus. She shared her concern with the doctor at her office who ordered an ANA which returned positive at 1:80 speckled ROS: (+) oral ulcers, joint pain, fatigue, chest pain that worsens with coughing or deep breathing, photophobia; rest (-) FSHx:Family history (-); ETOH (-); Tob (-); Works as a secretary in a dermatologist s office Meds: OCP PE:Vitals normal. Anxious-appearing; no joint swelling with full ROM; rest (-)
25 Not SLE Oh yeah, I forgot to mention she had tender points Diagnosis is? Canker sores are common Musculoskeletal chest pain is common Are you SURE I don t have lupus (or won t develop it later?) Kimmo et al: 1% developed SLE (w +ANA & no findings) Wijeyesinghe et al: < 10% developed SLE (with high titer ANA only)
26 30 yo woman with rash on her cheeks and joint pain. Found to have positive ANA. On exam, erythema on face, particularly around eyebrows, on cheeks and in nasolabial crease. No joint swelling (ROM nl). CBC, Creatinine and UA nl. Does she have SLE? Skip Ahead
27 No, she doesn t meet criteria What are her clinical manifestations that need intervention? Rash: Joint Pain (arthralgia NOT arthritis): Positive ANA: When would you see her back again?
28 She does well for 1 year with NSAIDs At follow up visit, she complains of more joint pain. On exam,she has joint swelling in her PIPs. CBC significant for WBC 2.9 (had been at past visits). Creatinine and UA nl. Does she have SLE? What requires intervention?
29 Prednisone 10 mg/day resolves swelling. A moderate taper is initiated (2.5 mg every 1-2 weeks)but her joints swell when dose drops below 5 mg/day. Hydroxychloroquine started.
30 Other labs: C3 40 (80-150) C4 8 (15-45) DsDNA strongly positive Sm/RNP/SSA/SSB negative Does she have SLE? Any consequences of delay in diagnosis or therapy? Use (trust) your clinical skills Follow up is important
31 Labs support a clinical impression!! RF found in up to 15% of General Population ANA found in 30% ANA titers do not correlate with disease activity DsDNA/Sm very specific for SLE RF/CCP in 80% of RA pts ANA in 93% SLE pts ESR is nonspecific C ANCA Wegener s (GPA) Proteinase 3 P ANCA MPA Myeloperoxidase ABY Additional Material for ABIM Exam
32
33 HLA-B27 Jo-1 (Histidine trna synthetase) SCL-70 (topoisomerase) RNA polymerase III Histone antibody HLA-DR4 Back
34 Substrate: Hep 2 cell line (human laryngeal carcinoma cell line) Back
35 Those you believe have a systemic autoimmune disease. Volkmann et al. Disabling fatigue (and not FMS or MDD) Raynaud s Joint pain/swelling High risk drugs Back
36 Volkmann et al. Low-titer ANA (1:40, 1:80) woadd lfindings no follow up Moderate titer ANA(1:160 1:640) woadd lfindings recheck ANA and exam Same or lower titer woadd lfindings no follow up Higher titer as below High titer ANA (> 1:640) follow every 6 months (SV stretch out follow up visits if negative) Back
APPROACH TO PATIENTS WITH POLYARTHRALGIA
APPROACH TO PATIENTS WITH POLYARTHRALGIA Scott Vogelgesang, MD Division of Immunology University of Iowa No conflicts of interest DEFINITIONS Arthralgia joint pain with no evidence of inflammation Arthritis
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