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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!

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Rheumatologic assessments l.jpg

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


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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


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    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


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    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


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    RED FLAG CONDITIONS

    • FRACTURE

    • SEPTIC ARTHRITIS

    • GOUT/PSEUDOGOUT


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    Key Questions

    • Inflammatory vs. Noninflammatory ?

    • Acute vs. Chronic ? (< or > 6 weeks)

    • Articular vs. Periarticular ?

    • Mono/Oligoarthritis vs Polyarthritis ?

      (Focal) (Widespread)

    • Are there RED FLAGS?


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    Inflammatory vs Noninflammatory


    Mono oligo vs polyarticular l.jpg

    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


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    Nonarticular Pain

    • Fibromyalgia

    • Fracture

    • Bursitis, Tendinitis, Enthesitis, Periostitis

    • Carpal tunnel syndrome

    • Polymyalgia rheumatica

    • Sickle Cell Crisis

    • Raynaud’s phenomenon

    • Reflex sympathetic dystrophy

    • Myxedema


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    Formulating a Differential Dx


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    Musculoskeletal Complaint

    • Initial Rheumatic History and Physical Exam to Determine:

      • 1. Is it articular

      • 2. Is it acute or chronic?

      • 3. Is inflammation present?

      • 4. How many/which joints are involved?

    • Nonarticular Condition

    • Trauma/Fracture

    • Fibromyalgia

    • Polymyalgia Rheumatica

    • Bursitis

    • Tendinitis

    Is it Articular?

    No

    Yes

    Is Complaint > 6 wks Duration?

    Yes

    No

    • Acute 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?

    Acute

    Chronic

    No

    Yes

    Chronic Inflammatory Arthritis

    • Chronic Inflammatory

    • Mono/oligoarthritis

    • Consider:

    • Indolent infection

    • Psoriatic Arthritis

    • Reiter’s Syndrome

    • Pauciarticular JA

    Chronic Noninflammatory Arthritis

    1-3

    How Many Joints Involved?

    Are DIP, CMC, Hip or

    Knee Involved?

    >3

    Chronic Inflammatory

    Polyarthritis

    No

    Yes

    No

    • Consider:

    • Psoriatic Arthritis

    • Reiter’s Syndrome

    Is it Symmetric?

    • Unlikely to be

    • Osteoarthritis

    • Consider:

    • Osteonecrosis

    • Charcot Arthritis

    Osteoarthritis

    Yes

    • Consider:

    • SLE

    • Scleroderma

    • Polymyositis

    Rheumatoid

    Arthritis

    Are PIP, MCP or MTP

    Joints Involved?

    No

    Yes


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    Musculoskeletal Complaint

    < 55 yrs.

    > 55 yrs.


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    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


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    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


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    Drug – Induced Syndromes

    • 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


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    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


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    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.


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    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?


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    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?


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    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?


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    Migratory Arthritis

    • Viral arthritis (hepatitis B)

    • Rheumatic fever

    • Gonococcal arthritis

    • SLE

    • Behcets

    • Hyperlipidemia


    Hepatitis b associated arthritis l.jpg

    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


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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

      • Finkelsteins ext.pollicis brevisDeQuervains tenosynovitis

      • 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

    • 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”


    Presbyterian hosp cheaposcreen l.jpg

    Presbyterian 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”


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    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 l.jpg

    Common Rheumatic Tests

    TestsSensitivitySpecificity

    Rheumatoid 80%95%

    Factor

    Antinuclear 98%93%

    Antibody

    Uric Acid63%96%


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    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


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    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 l.jpg

    ESR & Age

    M=Age/2

    F=Age+10/2


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    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


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    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


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    Joint Pain and ANA+

    • 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?


    Reasons for ana l.jpg

    Reasons for +ANA

    • Age

    • Drugs (thorazine, lithium, aldomet, tetracycline)

    • Drug induced lupus???

    • No reason: ANA is low titer nonspecfic pattern

    • No evidence of SLE


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    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


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    ANA PATTERNAg IdentifiedClinical Correlate

    DiffuseDeoxyRNPLow titer=Nonspecific

    HistonesDrug-induced lupus

    Peripheralds-DNA50% of SLE (specific)

    SpeckledU1-RNP>90% of MCTD

    Sm30% of SLE (specific)

    Ro (SS-A)Sjogrens 60%, SCLE

    Neonatal LE, ANA(-)LE

    La (SS-B)50% Sjogrens, 15% SLE

    Scl-7040% of PSS (diffuse dz)

    PM-1PM/DM

    Jo-1PM, Lung Dz, Arthritis

    NucleolarRNA Polymerase I, others 40% of PSS

    CentromereKinetochore75% CREST (limited dz)

    CytoplasmicRo, ribosomal PSS, SLE psychosis

    (nonspecific)CardiolipinThrombosis,Sp. Abort, Plts

    AMA, ASMAPBC, Chr. active hepatitis


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    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


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    ANA+ and Odds of SLE


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    Frequency in SLE

    AutoantibodyFrequency

    • dsDNA30-70%

    • Sm20-40%

    • RNP 40-60%

    • Ro10-15%

    • Ribosomal P5-10%

    • Histones30%

    • ACA40-50%

    Egner W, J Clin Pathol 53:424, 2000


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    ANA Associations

    Sensitivity (%)

    ConditionLaneKavanaugh

    • Drug-induced LE100

    • SLE 9995-100

    • Scleroderma9760-80

    • Sjogrens9640-70

    • MCTD93~100

    • PM/DM7830-80

    • RA4030-50

    • Vasculitis15

    • JRA20-50

    • Raynauds20-60

    Lane SK, Gravel JW, Am Fam Phys 65:1073, 2002

    Kavanaugh AF, et al; Arch Pathol Lab Med 124: 71, 2000


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    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


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    Rheumatoid Factor


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    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


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    Age and Serologic Testing


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    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.


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    CCP antibodies by ELISA

    AITD: autoimmune thyroid dz; MGUS-monoclonal gammopathy; NC-normals


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    Xray damage after 3 yrs in 178 RA patients assessed serologically

    Negative PPV: May be most important

    Van Jaarsveld CHM, et al. Clin Exp Rheumatol 17: 689, 1999


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    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


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    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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    Knee Joint Injection

    A Moran – Cush Video Exclusive


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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


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    Synovial Fluid Analysis


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