Overview of Rheumato..

Overview of Rheumatology Labs: Alphabet soup? Pediatric Rheumatology Red Team Resident Teaching Series

What are all those letters? • • • • • • • • • • •

ESR ANA CRP dsDNA ENA RNP Smith SS-a/SS-b Cardiolipin Jo-1 CPK

• • • • • • • • • • • •

p-ANCA/ c-ANCA RF C3/C4 CH50 Histone Centromere Scl-70 VDRL/RPR DRVVT Beta 2 glycoprotein 1 LDH Aldolase

Background • 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 (ESR) • 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 stress • 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 (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 Americans • 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 manifestations

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: • • • •

Procainamide Quinidine Hydralazine Phenytoin or other anti-epileptics

Antineutrophil Cytoplasmic Antibodies (ANCA) • Associated with vasculitides • Used as diagnostic test and possibly an evaluative test (still questionable) • 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 (