Overview of Rheumato..

Overview of
Rheumatology Labs:
Alphabet soup?
Pediatric Rheumatology
Red Team Resident
Teaching Series
What are all those letters?
Beta 2 glycoprotein 1
• Rheumatology spans a group of diseases that
have auto-immune components
• Proposed mechanisms to auto-immunity
including cross reactive antigens, molecular
mimicry, and autoantibody amplification
• We can identify auto-antibodies and therefore
characterize clinical diseases
• However, presence of auto-antibodies does not
always predict disease
Diagnostic vs. Evaluative Tests
• Need to distinguish to determine which test is appropriate
• Diagnostic tests accurately distinguish a group of patients with
a specific disease from a non-disease group
• Evaluative tests monitor disease activity over time
Erythrocyte Sedimentation Rate
• Mainly used as a disease activity indicator
• Method: Westergren method (most common) which
measures the rate of settling of RBCs in anticoagulated
whole blood
• Nonspecific test of inflammation
• Elevated in infection, IBD, cancer, pregnancy, trauma, and
• Can be falsely low in conditions that don’t let RBCs
undergo rouleaux formation (sickle cell anemia,
Hereditary Spherocytosis, CHF, polycythemia)
Anti-nuclear Antibodies (ANA)
• Immunoglobulins directed against structures within the cell (i.e.
DNA, ribonuclear proteins, histones, and centromere)
• Titer is important; pattern not important
• Found in a variety of autoimmune diseases such as SLE, MCTD,
JRA, scleroderma, Sjogren’s syndrome in high titers (>1:320)
• Almost always present in SLE (95-98%)
• Low titers (<= 1:160) found in:
• Infections (EBV, CMV, Hepatitis B, bacterial endocarditis, HIV)
• Drugs (hydralazine, INH, dilantin, tegretol, ETX, PCN, and sulfas)
• Neoplasias (lymphoma)
• It is sensitive but not that specific
• Consider using as a screening test in only symptomatic patients
• Approximately 10% of the population has a positive low titer ANA and
can be asymptomatic
• ANAs do not correlate with disease activity ( i.e. diagnostic test)
• If positive, should subtype (anti-dsDNA, ENA panel)
• Must measure ANAs in patients with JIA to assess risk of uveitis
ANA Subtype: Double Stranded DNA
Anti-dsDNA antibody is an ANA subtype
In higher titers, highly specific for SLE
Seen in >80% of SLE patients at some time during their course
Associated with the presence of active lupus nephritis
Can detect flare up before clinically significant
Check anti-dsDNA levels if you suspect SLE in a child with
positive ANA
ANA Subtype: Anti-Extractable
Nuclear Antibodies (anti-ENA)
• anti-Smith (Sm) and anti-ribonucleoprotein (RNP)
• Both are directed against RNA proteins and are readily
soluble in neutral buffers
• Anti-RNP is specific for MCTD (high titer)
• Anti-Sm ab is highly specific for SLE
• 10-20% in Caucasians, 30% in Asians, 40% in African
• One of the lupus criteria
ANA Subtype:
Anti Ro/SS-A and Anti La/SS-B
• Associated with Sjogren’s, SLE, and neonatal lupus
• Anti Ro/SS-A antibodies seen in:
• 5-15% of normals
• 50% of Sjogren’s patients
• 30% of SLE patients (many have negative ANA or subacute
cutaneous lupus)
• Correlates with active nephritis and cytopenias
• Crosses the placenta and is associated with neonatal SLE and
heart block
• Anti La/SS-B antibodies seen in:
5% of normals
15-85% of Sjogren’s patients
10-15% of SLE patients
Also associated with neonatal SLE but do not see the cardiac
ANA Subtype: Anticentromere, AntiScl-70, and Antihistone Antibodies
• Anticentromere Antibodies seen in limited cutaneous
systemic sclerosis
• Anti-Scl-70 Antibodies (also known as anti-topoisomerase I)
are assoicated with increased risk of pulmonary fibrosis in
both limited and diffuse cutaneous systemic sclerosis
• Anti-histone antibodies are found in 95% of patients with
drug-induced lupus syndrome
• Seen with:
Phenytoin or other anti-epileptics
Antineutrophil Cytoplasmic
Antibodies (ANCA)
• Associated with vasculitides
• Used as diagnostic test and possibly an evaluative test (still
• 2 main staining categories: c-ANCA and p-ANCA:
• Cytoplasmic ANCA (c-ANCA) – coarse granular staining of the
cytoplasm. The main antigen is proteinase-3 (PR3). Seen in 90%
of Wegener’s granulomatosis.
• Perinuclear ANCA (p-ANCA) – staining of the nucleus and
perinuclear area leaving cytoplasm clear. Main antigen is
myloperoxidase (MPO). Associated with microscopic polyarteritis
nodosa, Churg-Strauss, and Ulcerative Colitis.
Rheumatoid Factor (RF)
• Uncommon in children
• Should NOT be used as a screening test for rheumatic disease
in children
• Only indication is for polyarticular JIA patients to classify and
offer prognostic information
• Low titers seen in healthy children (<5%), infections (viral,
SBE), malignancy, SLE
• High titers seen in JIA (<20%) and predictive of erosive joint
disease (follows adult RA course more) and MCTD
• One of the histocompatibility genes
• Associated with seronegative spondyloarthropathies:
ankylosing spondylitis (AS) (up to 90%)
IBD (25-50%)
psoriatic arthritis (<25%)
reactive arthritis (50-75%)
• Less than 20% patients with HLA-B27 develop AS
• Used to document complement consumption and diagnose
rare complement deficiencies
• CH50 (overall complement level) is decreased in SLE, MCTD,
and immune complex vasculitis
• Most common congenital complement deficiency is C2
• Low C3 and C4 levels seen in active lupus
• Complement levels help follow disease activity and response
to treatment in SLE
• Considered a diagnostic and evaluative test
Antiphospholipid Antibodies (aPL
• Group of antibodies against a variety of phospholipids and
phospholipid binding plasma proteins
• Associated with syndrome of coagulopathy,
thrombocytopenia, recurrent spontaneous abortions, livedo
reticularis, migraines, TTP, chorea, myelitis, and avascular
necrosis of bone
• Can occur with SLE (30-40%), or seen without other
autoimmune disease (antiphospholipid antibody syndrome)
1. Positive anti-cardiolipin antibodies (aCL)
IgG – associated with thrombosis
IgM – associated with thrombocytopenia only
Positive lupus anticoagulant: misnomer; antibody on
the phospholipid of the prothrombin activator complex
that causes in vitro anticoagulation (elevated aPTT and
positive DRVVT) but in vivo paradoxical thrombosis
Dilute Russell Viper Venom Test (DRVVT)
β2glycoprotein-1 IgG and IgM
Practice Question #1a
• A 3 year old girl with a two month history of a swollen and
painful knee and eye findings
Practice Question #1b
• A 15 year old girl with multiple joint pains and joint swelling
Practice Question #1c
• A 8 yo boy with persistent fevers, intermittent rashes, and
joint pain
Answer for Question 1a-c: Juvenile
Idiopathic Arthritis
ANA to determine uveitis risk
If polyarticular course, add RF
If older onset with sacroiliac tenderness and tendon insertion
site tenderness, add HLA-B27
• If systemic course, add LFTs, Ferritin, DDimer
Practice Question #2
• A 13 year old Hispanic girl with a facial rash, joint pain, mouth
sores, fatigue, and blood in her urine
Answer for Question #2: Systemic
Lupus Erythematosus
C3/C4 levels
Urinalysis and Urine protein/creatinine ratio
Antiphospholipid Antibodies (Anti-cardiolipin ab, PTT,
DRVVT, and LAC, B2glycoprotein)
Practice Question #3
• A 6 year old boy with muscle weakness, leg pains, and rash
over his eyelids and on his elbows
Answer for Question #3:
CPK, Aldolase, LDH (muscle enzymes)
AST/ALT (in this case, as a muscle enzyme)

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