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Rheumatologic Assessments
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What is needed to establish a differential diagnosis
Consider the most common conditions
Diagnosis by:
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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
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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
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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
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Goals of Assessment
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Identify “Red Flag” conditions
 Conditions
with sufficient morbidity/mortality to warrant an
expedited diagnosis
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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
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Provide relief, reassurance and plan for evaluation
and treatment
RED FLAG CONDITIONS
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FRACTURE
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SEPTIC ARTHRITIS
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GOUT/PSEUDOGOUT
Key Questions
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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
Mono/Oligo vs Polyarticular
Monarticular
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Osteoarthritis
Fracture
Osteonecrosis
Gout or Pseudogout
Septic arthritis
Lyme disease
Reactive arthrtis
Tuberculous/Fungal arthritis
Sarcoidosis
Polyarticular
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Osteoarthritis
Rheumatoid arthritis
Psoriatic arthritis
Viral arthritis
Serum Sickness
Juvenile arthritis
SLE/PSS/MCTD
Nonarticular Pain
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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
Initial Rheumatic History and Physical Exam to Determine:
1.
2.
3.
4.
Nonarticular Condition
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Trauma/Fracture
Fibromyalgia
Polymyalgia Rheumatica
Bursitis
Tendinitis
Is it articular
Is it acute or chronic?
Is inflammation present?
How many/which joints are involved?
Is it Articular?
No
Yes
Is Complaint > 6 wks Duration?
No
Acute Arthritis
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Infectious Arthritis
Gout
Pseudogout
Reiter’s Syndrome
Yes
Acute
Chronic
• Initial Presentation of
Chronic Arthritis
Is Inflammation Present?
1.
2.
3.
4.
Is there prolonged morning stiffness?
Is there soft tissue swelling?
Are there systemic symptoms?
Is the ESR or CRP elevated?
No
Yes
Chronic Inflammatory Arthritis
Chronic Noninflammatory Arthritis
Are DIP, CMC, Hip or
Knee Involved?
No
Yes
Chronic Inflammatory
Mono/oligoarthritis
Consider:
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1-3
How Many Joints Involved?
Indolent infection
Psoriatic Arthritis
Reiter’s Syndrome
Pauciarticular JA
>3
Chronic Inflammatory
Polyarthritis
No
Consider:
Unlikely to be
Osteoarthritis
Consider:
• Osteonecrosis
• Charcot Arthritis
Osteoarthritis
• Psoriatic Arthritis
• Reiter’s Syndrome
Consider:
• SLE
• Scleroderma
• Polymyositis
No
Is it Symmetric?
Yes
Are PIP, MCP or MTP
Joints Involved?
Yes
Rheumatoid
Arthritis
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
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Age
Young: JRA, SLE, Reiter's, GC arthritis
 Middle: Fibromyalgia, tendinitis, bursitis, LBP RA
 Elderly: OA, crystals, PMR, septic, osteoporosis
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Sex
Males: Gout, AS, Reiter's syndrome
 Females: Fibrositis, RA, SLE, osteoarthritis
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Race
White: PMR, GCA and Wegener's
 Black: SLE, sarcoidosis
 Asian: RA, SLE, Takayasu's arteritis, Behcet's
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Onset & Chronology
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Acute: Fracture, septic arthritis, gout, rheumatic fever,
Reiter's syndrome
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Chronic: OA, RA, SLE, psoriatic arthritis, fibromyalgia
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Intermittent: gout, pseudogout, Lyme, palindromic
rheumatism, Behcet's, Familial Mediterranean Fever
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Additive: OA, RA, Reiter's syndrome, psoriatic
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Migratory: Viral arthritis (hepatitis B), rheumatic fever,
GC arthritis, SLE
Drug – Induced Syndromes
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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
Rheumatic Review of Systems
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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
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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
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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
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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
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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
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Viral arthritis (hepatitis B)
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Rheumatic fever
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Gonococcal arthritis
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SLE
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Behcets
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Hyperlipidemia
Hepatitis B Associated Arthritis
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Arthritis and urticaria part of the “prodrome”
Manifestations due to immune complex deposition
 Before the Jaundice
 Usually while LFTs elevated
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Acute onset
Additive (RA like) or migratory (ARF like) arthritis
Often with tenosynovitis
Synovial fluid: inflammatory
Arthritis disappears with onset of Jaundice
Musculoskeletal Exam
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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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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
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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”

Presbyterian 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
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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)
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Common Rheumatic Tests
Tests
Rheumatoid
Factor
Antinuclear
Antibody
Uric Acid
Sensitivity
Specificity
80%
95%
98%
93%
63%
96%
Acute Phase Reactants
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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
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ESR : Introduced by Fahraeus 1918
Mechanisms: Rouleaux formation
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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
ACP Recommendations for Diagnostic Use of
Erythrocyte Sedimentation Rate
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The ESR should not be used to screen asymptomatic persons for disease
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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
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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
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The ESR is indicated for the diagnosis and monitoring of temporal arteritis and
polymyalgia rheumatica
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In diagnosing and monitoring patients with rheumatoid arthritis, the ESR should
be used prinicipally to resolve conflicting clinical evidence
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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
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Joint Pain and ANA+
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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
1.
2.
3.
4.
5.
Age
Drugs (thorazine, lithium, aldomet, tetracycline)
Drug induced lupus???
No reason: ANA is low titer nonspecfic pattern
No evidence of SLE
Antinuclear Antibodies
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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
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Not synonymous with a Dx of SLE
May be present in other conditions:
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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
ANA Associations
Condition
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Drug-induced LE
SLE
Scleroderma
Sjogrens
MCTD
PM/DM
RA
Vasculitis
JRA
Raynauds
Sensitivity (%)
Lane
Kavanaugh
100
99
97
96
93
78
40
15
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Lane SK, Gravel JW, Am Fam Phys 65:1073, 2002
Kavanaugh AF, et al; Arch Pathol Lab Med 124: 71, 2000
95-100
60-80
40-70
~100
30-80
30-50
20-50
20-60
Antiphospholipid Syndrome
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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
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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%
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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%

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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
CCP Antibodies
(cyclic citrullinated peptide Abs)
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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
Negative PPV: May be most important
Van Jaarsveld CHM, et al. Clin Exp Rheumatol 17: 689, 1999
ANCA: Anti-Neutrophil
Cytoplasmic Antibodies
 C-ANCA, P-ANCA, myeloperoxidase (MPO),
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

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
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
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Class I MHC Ag, associated with the
spondyloarthropathies
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HLA-27 is found in up to 8% of normals
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
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
Knee Joint Injection
A Moran – Cush Video Exclusive
Indications for Arthrocentesis
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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
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