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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
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
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
Uncommon Causes of Joint PainUncommon Causes of Joint Pain
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 NoninflammatoryFeatureInflammatoryNoninflammatoryPain (worse when?)Yes (morning)Yes (night)SwellingSoft Tissue (+ effusion)Bony ErythemaSometimes PresentAbsentWarmthSometimes PresentAbsentMorning StiffnessProminent ( > 1 hr.) Minor ( < 45 min.)Systemic Features+Sometimes PresentAbsentElevated ESR or CRP*FrequentUncommonSynovial Fluid WBCWBC > 2,000 /mm3WBC < 2,000 /mm3ExamplesSeptic arthritis, RA, Gout,Polymyalgia rheumaticaOsteoarthritis, AdhesiveCapsulitis,Osteonecrosis+ fever, rash, weight loss, anorexia, anemia * ESR: erythrocyte sedimentation rate; CRP: C-reactive protein
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
Articular NonarticularInflammatory Septic
Gout
Rheumatoid arthritis
Psoriatic arthritis
Bursitis
Enthesitis
PMR
Polymyositis
Noninflammatory Osteoarthritis
Charcot Joint
Fracture
Fibromyalgia
Carpal tunnel
RSD
Musculoskeletal Complaint Initial Rheumatic History and Physical Exam to Determine:1. Is it articular2. Is it acute or chronic?3. Is inflammation present?4. How many/which joints are involved?
Is it Articular?
Is Complaint > 6 wks Duration?
Nonarticular Condition• Trauma/Fracture• Fibromyalgia• Polymyalgia Rheumatica• Bursitis• Tendinitis
ChronicAcuteAcute Arthritis
• Infectious Arthritis• Gout• Pseudogout• Reiter’s Syndrome
• Initial Presentation of Chronic Arthritis
Is Inflammation Present?1. Is there prolonged morning stiffness?2. Is there soft tissue swelling?3. Are there systemic symptoms?4. Is the ESR or CRP elevated?
Chronic Inflammatory Arthritis
Chronic Noninflammatory ArthritisHow Many Joints Involved?
Chronic InflammatoryMono/oligoarthritisConsider:• Indolent infection• Psoriatic Arthritis• Reiter’s Syndrome• Pauciarticular JA
Are DIP, CMC, Hip orKnee Involved?
Unlikely to be OsteoarthritisConsider:• Osteonecrosis• Charcot Arthritis
Osteoarthritis
Chronic InflammatoryPolyarthritis
Is it Symmetric?
Are PIP, MCP or MTPJoints Involved?
Consider:• SLE• Scleroderma• Polymyositis
Consider: • Psoriatic Arthritis• Reiter’s Syndrome
Rheumatoid Arthritis
Yes
No
Yes
Yes
No
No
No
Yes
Yes
NoNo Yes
1-3
>3
TraumaFracture
Orthopedic Evaluation
InfectiousArthritis
(GC, Viral,Bacterial, Lyme)
PsoriaticReiters
IBD Arthritis
RheumatoidArthritis
Gout(males only)
Repetitive Strain Injury(carpal tunnel,bursitis)
SepticArthritis
(Bacterial)
OsteoporoticFracture
PolymyalgiaRheumatica
GoutPseudogout
Osteoarthritis
Fibromyalgia
Low BackPain?
Musculoskeletal Complaint
< 55 yrs. > 55 yrs.
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, palindromic rheumatism, Behcet's, Familial Mediterranean Fever
Additive: OA, RA, Reiter's syndrome, psoriatic
Migratory: Viral arthritis (hepatitis B), rheumatic fever, GC arthritis, SLE
Arthralgias: Quinidine, amphotericin B, cimetadine, quinolones, chronic acyclovir, interferon, IL-2, nicardipine, vaccines
Myalgias/myopathy: Steroids, penicillamine, hydroxychloroquine, AZT, lovastatin, clofibrate, interferon, IL-2, alcohol, cocaine, taxol, colchicine, tryptophan
Gout: Diuretics, ASA, cytotoxics, cyclosporine, alcohol, moonshine, ethambutol
Drug-induced lupus: hydralazine, procainamide, quinidine, methyldopa, INH phenytoin, chlorpromazine, lithium, penicillamine, TCN, TNF inhibitors
Osteopenia: Steroids, chronic heparin, phenytoin, methotrexate Osteonecrosis: Steroids, alcohol, radiation therapy Scleroderma/tight skin: Vinyl chloride, bleomycin, pentazocine, solvents,
carbidopa, tryptophan, rapeseed oil Vasculitis: Allopurinol, amphetamines, cocaine, LSD, thiazide,
penicillamine, propylthiouracil
Drug – Induced Syndromes
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
Acute Onset Arthritis 28 yr. old WF presents with acute onset of knee
swelling and pain 7 days ago. Two days later, knee resolved but both wrists began to swell. On day 7, the wrists improved but all PIPs were swollen and tender.
By day 10 she complained of arthritis in PIPs, wrists, knees and ankles. + Tenosynovitis L wrist. AM stiffness was 4 hours. C/O fatigue. Denies fever, rash
She visits her PCP who examines her and orders “Rheumatoscreen Plus” and XRAYs.
He sends her home on OTC ibuprofen, tylenol and Vicks Vapo-Rub.
Acute Onset Arthritis/Rash Day 14 she returns to PCP with
low grade fever, rash (pruritic) on the trunk and extremities.
Exam: symmetric polyarthritis in an RA-like distribution. Tenosynovitis has resolved. Urticarial lesions over trunk and extensor surface of arms. (+)2 cm nontender, left axillary LN. No malar rash, nodules, acne, or Raynauds phenomena.
Investigations?
Acute Onset Migratory Arthritis WBC = 11.2 H/H = 13.7 / 38.9 MCV = 89 ESR = 123 mm/hr SMA-12 WNL, except albumin = 3.3, AST-67, ALT 77 ANA negative RF 31 IU/ml (nl < 30 IU/ ml) C3 173, C4 28, ASO = 151 Todd units Uric Acid = 6.6 Normal SPEP, UPEP, TFT’s, TSH, Ferritin Others?
Acute Onset Arthritis/Rash She returns after 1 wk for LN Bx results (negative) Pt. states her rash and arthritis have nearly
resolved. Exam confirms only mild swelling in knees However, her sclera are definitely icteric. Next?
Migratory Arthritis Viral arthritis (hepatitis B)
Rheumatic fever
Gonococcal arthritis
SLE
Behcets
Hyperlipidemia
Hepatitis B Associated Arthritis
Arthritis and urticaria part of the “prodrome” Manifestations due to immune complex deposition Before the Jaundice Usually while LFTs elevated
Acute onset Additive (RA like) or migratory (ARF like) arthritis Often with tenosynovitis Synovial fluid: inflammatory Arthritis disappears with onset of Jaundice
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 Finkelsteins ext.pollicis brevisDeQuervains tenosynovitis Bulge sign Syn.Fluid Suprapatellar pouch Knee effusion Drop arm sign Complete Rotator Cuff TearTrauma? McMurray sign Torque on Meniscus Cartilage Tear
Right Joint Left
TMJ
SC
AC
Shoulder
Elbow
Wrist
CMC1
MCP 1-5
PIP 1-5
Hip
Knee
Ankle
Tarsus
MTP 1-5
Toe 1-5
RHEUMATOSCREEN PLUS
CBC & differential Chem-20 Uric acid Urinalysis ESR C-reactive protein RPR CPK Aldolase ASO Immune complexs TFT’s 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”
ANA+
RF
CBC & diff $35.00
Chem-20 $108.00
Urinalysis $30.00
ESR or CRP $25.30
Uric acid $40.00
$ 238.30
CUSHY LABS INC. “YOUR INDECISION IS OUR BREAD AND BUTTER”
Presbyterian Hosp. CheapoScreen
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 Sensitivity Specificity
Rheumatoid 80% 95%
Factor
Antinuclear 98% 93%
Antibody
Uric Acid 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
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
Erythrocyte Sedimentation Rate
ESR & Age
0
10
20
30
40
50
60
ESR mm/hr
<30 30-39 40-49 50-59 60-69 70-79 80-89
Age (years)
M=Age/2F=Age+10/2
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
Joint Pain and ANA+ 79 yoWM with schizophrenia and heart failure
presents with a 3 month hx of arthralgias affecting the knees, shoulders, elbows. His MD found +ANA 1:80
He complains of rashes, fever Says your stethoscope looks like a snake PMHx: as above, Meds: Lithium, Thorazine, aldomet, acromycin
VS: T=98.7 BP=110/75 R=18 P=88 Alert and oriented x 3 CVS exam: deferred Skin: Seborrheic dermatitis Joints: tender muscles and joints. No synovitis Labs: W 5.2, H/H 13/39, P178k, ESR 38, neg RF,
+ANA 1:80 speckled pattern Other tests? Diagnosis?
Joint Pain and ANA+
Reasons for +ANA
1. Age
2. Drugs (thorazine, lithium, aldomet, tetracycline)
3. Drug induced lupus???
4. No reason: ANA is low titer nonspecfic pattern
5. No evidence of SLE
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 Low titer=Nonspecific
Histones Drug-induced lupus
Peripheral ds-DNA 50% of SLE (specific)
Speckled U1-RNP >90% of MCTDSm 30% of SLE (specific)Ro (SS-A) Sjogrens 60%, SCLE
Neonatal LE, ANA(-)LELa (SS-B) 50% Sjogrens, 15% SLEScl-70 40% of PSS (diffuse dz)PM-1 PM/DMJo-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
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
ANA+ and Odds of SLE
0
1020
30
4050
6070
80
90100
1 2 3 4 5 6
Percent
criteria +ANA
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
ANA Associations Sensitivity (%)
Condition Lane Kavanaugh Drug-induced LE 100 SLE 99 95-100 Scleroderma 97 60-80 Sjogrens 96 40-70 MCTD 93 ~100 PM/DM 78 30-80 RA 40 30-50 Vasculitis 15 JRA 20-50 Raynauds 20-60
Lane SK, Gravel JW, Am Fam Phys 65:1073, 2002Kavanaugh AF, et al; Arch Pathol Lab Med 124: 71, 2000
Antiphospholipid Syndrome Triad
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
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% 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
Age and Serologic Testing
0
2
4
6
8
10
12
14
16
percent (+)
20-30 yrs > 65 yrs
ANA RF
CCP Antibodies(cyclic citrullinated peptide Abs)
Antibodies directed against Citrulline proteins AKA anti-filaggrin, anti-keratin and anti-perinuclear factor
antibodies (all identify filaggrin – citrulline rich) Citrulline is a post-translationally modified arginine residue that
binds “shared epitopes” (HLA-DR4 (HLADRB1 *0401, *0404) suggesting CCP Abs may play a role in RA pathogenesis .
Method: 2nd generation assay is widely available as EIA; has greater sensitivity than earlier version
Increased in: RA (sensitivity 50-70%); early RA (40-60%), RA with severe erosive disease. Specificity (95%) is higher than RF. CCP may be prognostically important in new onset RA
Indications: Suspected RA, new onset RA.
CCP antibodies by ELISA
AITD: autoimmune thyroid dz; MGUS-monoclonal gammopathy; NC-normals
Xray damage after 3 yrs in 178 RA patients assessed serologically
Van Jaarsveld CHM, et al. Clin Exp Rheumatol 17: 689, 1999Van Jaarsveld CHM, et al. Clin Exp Rheumatol 17: 689, 1999
Negative PPV: May be most important
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 GoutSerum Urate mg/dl Gout
Incidence/yr/1000
5 year 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 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
Knee Joint Injection
A Moran – Cush Video Exclusive
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
Noninflammatory Type I
Inflammatory
Type II
Septic
Type III
Hemorrhagic
Type IV
Appearance Amber-yellow Yellow Purulent Bloody
Clarity 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
TraumaFracture
Ligament tearCharcot Jt.
PVS
Synovial Fluid Analysis