Paraclinic evaluation
in rheumatic diseases
Anousheh Haghighi
M.D. Rheumatologist
Laboratory testing is often valuable for :
Screening for diseases
Confirming diagnosis
Determining prognosis
Following response to therapy
Erythrocyte Sedimentation Rate
Fibrinogen and immunoglobulin levels
increase during the acute phase response.
When RBCs interact with these proteins, they
form clusters that sediment at a faster rate
than individual RBCs.
ESR increases with age and is somewhat
higher in women.
man<age/2
woman <(age+10)2
High ESR:
 Inflammation
 Infection
 Neoplasm
 Any condition that rises serum
fibrinogen(diabetes, ESRD, pregnancy)
Factors That Influence Erythrocyte
Sedimentation Rate
Increase
Anemia
Hypercholesterolemia
Female sex
High room temperature
Inflammatory disease
Chronic renal failure
obesity
Heparin
Tissue damage
Pregnancy
Decrease
RBC wall deformity
Polycythemia
Bile salt
low room temperature
Hypofibrinogenemia
Congestive renal failure
Cachexia
Clotting of blood sample
Greater than 2h delay in
running test
C-Reactive protein
CRP is an acute phase protein synthesized in
response to tissue injury.
CRP levels changes more quickly than the ESR
(increases within 4-6 hours and normalized
within a week)
CRP is affected by age and gender as is the ESR
Other disease processes including heart
disease, obesity, diabetes and cigarette
smoking can lead to CRP elevations
Rheumatoid factor
RF is an autoantibody (IgM, IgG, IgA) that
binds to the Fc region of human IgG.
Titers greater than 1/20 are positive
In established RA: sensitivity 70%
In early RA: sensitivity 50%
Rheumatoid factor
RF can be found in: other autoimmune
diseases, mixed essential cryoglobulinemia,
chronic infections, sarcoidosis, malignancy,
small percentage of healthy people.
IgA is a type has been linked to erosive disease
and to rheumatoid vasculitis
Higher titers of RF are associated with more
severe disease
RF is not used for monitoring disease activity
Anti-cyclic Citrollinated peptide
antibody
 Anti-ccp are autoantibodies directed against the
amino-acids formed by the posttranslational
modification of arginine.
 Sensitivity: similar to RF
 Specificity: more than RF
 Anti-ccp antibodies are often detectable in early RA
and in some cases, antedate the onset of inflammatory
synovitis.
 Anti-ccp antibodies are a better predictor of erosive
disease
 Anti-ccp antibodies do not correlate with extraarticular disease
Anitnuclear antibodies
ANAs are a diverse group of autoantibodies
that react with antigens in the cell nucleus.
ANA-negative lupus is virtually nonexistent
Up to 30% of healthy people may have a
positive titer
The prevalence of positive ANAs increases in
women and older people
Antinuclear Antibody: Peripheral
Pattern
Antinuclear Antibody: Diffuse Pattern
Antinuclear Antibody: Speckled
Pattern
Antinuclear Antibody: Nucleolar
Pattern
Antiphospholipid Antibody
Aticardiolipin antibody of IgG
and/or IgM isotype in blood,
present in medium or high titer, on
two or more occasions, at least 3
months apart, measured by a
standard
enzyme-linked
immunosorbant assay for beta2glycoprotein
I-dependent
anticardiolipin antibodies.
Anti-B2-Glycoprotein 1
Anti-B2- Gycoprotein 1 antibody of IgG or
IgM isotype in serum plasma present on
two or more occasions at least 3 months
apart, measured by standardized ELISA.
Lupus Anticoagulant
Lupus
anticoagulant
present
in
plasma on two or more occasions at
least 3 months apart, detected
according to the guidelines of the
International Society on Thrombosis
and Hemostasis.
Complement
 Decreased serum levels of individual components
especially C3 & C4 correlate with the increased
consumption observed in active immune complex
mediated disease, for example SLE.
 In contrast most inflammatory disorders that are
not associated with immune complex deposition
demonstrate elevated levels of complement
because these proteins are acute phase reactants
Complement
At least 30 protein, clinical use (C3, C4,
CH50)
Decreased: SLE, SBE, PSGN, vasculitis
(PAN associated with HBS Ag,
cryoglobulinemia), inherited deficiency
Increased: acute phase reactant
Cryoglobulines
 Cryoglobulins are immunoglobulins that precipitate
reversibly at cold temperatures.
 Based on their composition, cryoglobulins are classified
into three types:
 Type 1: monoclonal immunoglobulins, frequently of
IgM isotype
 Type 2: mixture of polyclonal IgGs & monoclonal IgM
 Type 3: combination of polyclonal IgGs & polyclonal
IgMs
 in both type 2 & 3, the IgM component has RF activity
 Cryoglobulins are not specific for any disease
Cryoglobulines
Type one cryoglobulins are linked to
lymphoproliferative disorders, malignancies
and hyperviscosity syndromes.
Type two and three cryoglobulins are
associated with hepatitis C virus infections
and a syndrome of small vessel vasculitis.
Cryoglobulinemia: Serum
Antineutrophil cytoplasmic
Autoantibodies
Antinuclear Cytoplasmic Antibody
 ANCAs are autoantibodies that react with
cytoplasmic granules of neutrophils.
 Two general staning patterns, cytoplasmic (CANCA) or perinuclear (P-ANCA) can be detected
by IF.
 These patterns reflect autoantibodies to two
lysosomal granule enzymes: PR3 & MPO
 Combination of C-ANCA & PR3-ANCA has a high
positive predictive value for ANCA-Associated
vasculitis particularly WG.
Antineutrophil Cytoplasmic
Antibody
The more active & extensive the vasculitis, the
more likely are ANCA assays to be positive.
ANCA titers often normalize with treatment
but do not always do so, even if clinical
remissions are achieved.
A persistent rise in ANCA titer or return of
ANCA positivity heralds an increased risk of
recurrent disease.
Anticytoplasmic Autoantibody
C-ANCA
Wegener’s
75-80%
Microscopic PAN 25-35%
Churg strauss
25-30%
RA-Felty syndrome
SLE
IBD (ulcerative colitis)
P-ANCA
10-15%
50-60%
25-30%
30-70%
20-30%
40-70%
Negative
5-10%
5-10%
40-50%
Synovial Fluid Analysis
Despite the development of increasingly
sophisticated serologic tests & imaging
techniques, SF analysis remains one of the
most important diagnostic tools in
rheumatology.
Indications for Arthrocentesis
Acute inflammatory monoarticular arthritis
Chronic monoarthritis
Polyarticular arthritis
Monoarticular arthritis in a patient with stable
polyarthritis
Therapeutic arthrocentesis
Synovial Fluid Analysis
Mucin Clot Test
Diagnosis by synovial class
Crystals
Strach and Cholesrol Crystals
Synovial Biopsy
Granulomatous diseases
Malignant infiltrations of the synovium
Infiltrative nonmalignant processes (Amyloid
arthropathy, hemochromatosis, ochronosis,
multicentric reticulohistocytosis)