Diagnostics Flashcards
How to diagnose a rheumatological disease?
H&P
Labs/radiographic findings- confirmatory
Define Sensitivity
Proportion of patients with positive test who have the disease
Define Specificity
Proportion of patients with negative test who do not have the disease
H&P in Rheumatologic Diseases
Increase “pretest probability” with history
Look for clues on physical exam
When to Order Serologic Tests
Assist in confirming a specific diagnosis
Formulate appropriate management
Evaluate/monitor disease activity
Define Acute Phase Reactants
Proteins synthesized by the liver and induced by inflammation and tissue injury/necrosis
Define Erythrocyte Sedimentation Rate (ESR)
Distance at which erythrocytes have settled in a vertical column of anticoagulated blood in an hour (mm/hr)
ESR Measurement
Indirect measurement of serum acute phase reactant concentrations
ESR Influenced by
Size
Shape
Number of RBCs
ESR Increased by
Acute phase reactants Paraproteins Anemia (fewer, less repellent forces) Age Gender Pregnancy DM Renal failure Malignancy Tissue damage
ESR in Polymyalgia Rheumatica
ESR >40 mm/hr
ESR in Giant Cell Arteritis
ESR >90 mm/hr
Define C-Reactive Protein (CRP)
Acute phase protein produced by the liver
What is CRP produced in response to and enhance?
Produced in response to inflammation
Enhances complement binding & phagocytosis
What does CRP measure?
Direct measure of acute phase reactants
Pros & Cons of CRP
Pro: responds more quickly
Cons: more expensive, don’t always know how to interpret
Define Rheumatoid Factor
Auto antibody directed against Fc portion of IgG
Conditions Causing Positive Rheumatoid Factor
SLE Scleroderma Sjogren syndrome Cryoglobulinemia Infections: hepatitis, TB, SBE, syphillis, parasitic disease, viral Pulmonary diseases Malignancy
Define Post Test Probability
Probability that the patient has the disease given a positive test result
How is rheumatoid factor measured?
Less than 1:80 is negative
Anti-CCP (citrulline antibody)
Antibody directed against “citrullinated” peptide residues present within inflammatory sites
Anti-CCP vs. RF
Sensitivity equal
Specificity: anti-CCP > RF
Anti-Nuclear Antibodies (ANA)
Autoantibodies directed at nuclear antigens or content of the cell nucleus
What is a serologic hallmark of systemic autoimmune disease?
ANAs
Uses of ANA
Help establish diagnosis when suggestive of an autoimmune or connective tissue disorder
Exclude such disorders with uncertain clinical findings
Subclassify a patient with an established diagnosis of an autoimmune or connective tissue disease
Monitor disease activity
When is a positive ANA seen?
Systemic autoimmune disease
Organ-specific immune diseases
Variety of infections
Normal individuals
Non-Rheumatic Conditions Causing Positive ANA
Normal individuals Hepatic diseases Pulmonary diseases Chronic infections Malignancies Hematologic disorders Drug-induced Misc: autoimmune thyroiditis, DM1
Criteria for Classification of SLE (Need 4+)
Malar rash Discoid rash Photosensitivity Oral ulcers Arthritis Serositis Neurologic disorder Renal disorder: proteinuria or casts Hematologic disorder: leukopenia, lymphocytopenia, or thrombocytopenia Immunologic disorders: antiphopholipid antibody, abnormal titer of anti-nDNA, anti-Sm, confirmed false + STS Positive antinuclear antibody
When to Order an ANA
Moderate pre-test probability: 3/11 lupus criteria
ANA Specific Autoantibody Tests
Anti-dsDNA Anti-Sm Anti-centromere antibody (ACA) Anti-topoisomerase I (Scl-70) Anti-Ro (SS-A) and Anti-La (SS-B) Anti-U1 snRNP Anti-Jo-1 (anti-histidyl-tRNA synthestase)
Anti-dsDNA
Specific for SLE
May fluctuate with disease activity
Anti-Sm (Smith antigen)
Highly specific for SLE
Anti-Centromere Antibody (ACA)
Associated with CREST & scleroderma
Anti-Topoisomerase I (Scl-70)
Associated with diffuse scleroderma
Anti-RO (SS-A) & Anti- La (SS-B)
Associated with Sjogren’s
Can be seen in SLE
Maybe associated with neonatal heart block in babies of mothers with antibody
Anti-U1 snRNP
Part of criteria for Mixed Connective Tissue Disease (MCTD)
May be seen in other rheumatic diseases
Anti-Jo-1 (anti-histidyl-tRNA synthestase)
Specific for myositis associated with interstitial lung disease
Raynaud’s
Use of Serum Complements
Monitoring disease activity in SLE
Low C3, C4 Levels
Reflect consumption of complement
Active SLE
Antineutrophil Cytoplasmic Antibodies
Group of autoantibodies mainly of the IgG type directed against antigens in the cytoplasm of neutrophil granulocytes & monocytes
P-ANCA: perinuclear
C-ANCA: cytoplasmic
ANCA Association
Vasculitis
Most Common Rheumatologic Disorder with a Positive C-ANCA
Wegener’s granulomatosis
Microscopic polyangiitis
Most Common Rheumatologic Disorder with a Positive P-ANCA
Churg-Strauss vasculitis
Human Leukocyte Antigen (HLA-B27)
Ankylosing spondylitis
Reactive arthritis
Enteropathic spondylitis
Psoriatic spondylitis
Diagnosing Ankylosing Spondylitis
Inflammatory back pain of insidious onset, worse in the morning, better with exercise & NSAIDs
Radiographic evidence
HLA-B27 positive
Relative Contraindications of Arthrocentesis
Overlying skin infection
Bleeding diathesis
Complications of Arthrocentesis
Infection
Bleeding
Cartilage injury
Vasovagal episode
Define Uric Acid
By-product of purine (adenine, guanine) catabolism
2 Mechanisms of Hyperuricemia
Increased production
Decreased excretion
Reasons for Increased Production of Uric Acid
Dietary purines (meat, yeast/beer, beans) Endogenous purine synthesis (CA) Tissue nucleic acid breakdown (chemo, hemolysis)
Reasons for Decreased Excretion of Uric Acid
Renal failure
Inhibition of tubular rate secretion (ketoacidosis)
Enhanced tubular rate reabsorption (diuretics, insulin resistance, dehydration)
Uric Acid Increased by What Medications
Low-dose ASA
ETOH
Caffeine
Vitamin C
Uric Acid Decreased by What Medications
High-dose ASA
Estrogens
Corticosteroids
Clinical Significance of Elevated Uric Acid
Gout Asymptomatic hyperuricemia Renal impairment Toxemia of pregnancy Conditions associated with increased production
Define Gout
Joint pain with swelling & erythema
Deposition of sodium urate crystals in joints & tissues
Parts of CREST Syndrome
Calcinosis Raynaud's Esophageal dysmotility Sclerodactyly Telangectasias
Systemic Sclerosis Characterized by
Functional & structural abnormalities of small blood vessels, fibrosis of skin & organs, & autoantibodies
Sjogren’s Syndrome Characterized by
Diminished lacrimal & salivary gland secretion (sicca syndrome)
Define Mixed Connective Tissue Disorder (MCTD)
Syndrome of overlapping disease manifestations with features of RA, SLE, scleroderma, & polymyositis
Define Dermatomyositis
Inflammatory myopathy with cutaneous lesions & muscle pain & weakness
Polymyositis Characterized by
Progressive muscle pain & weakness
