Clinical Serology and Laboratory Testing in Rheumatic Diseases

Question 1

Markers of inflammation

• ESR – Rises with age, higher in women – Monitor disease activity, especially PMR (polymyalgia rheumatica) and GCA (giant cell arteritis)

• CRP – Assessment of disease activity – Synthesized in liver – Proinflammatory cytokines increase CRP – Can activate complement, promote phagocytosis

Greater than 8 mg/l is inflammatory

-Rises and falls quicker than ESR

Answer 1

increase with inflammation

1. Leukocytosis,
2. thrombocytosis,
3. ferritin,
4. fibrinogen
5. complement

Question 2

Rheumatoid Factor (RF)

1. Is an IgM autoantibody that targets the Fc portion of IgG immunoglobulin
2. Can be any immunoglobulin subclass (IgA, IgG, IgM); IgM is most common
3. produced by B cells in synovial joints of RA patients

cut off valve for positive RF depends on lab methods:

positive RF > 45 IU/ml by ELISA or > 1:80 by latex fixation

Answer 2

positive in other conditiona other than RA

Sjögrens syndrome 95%

– Cryoglobulinemia 40‐100%

– Primary biliary cirrhosis 70%

– Mixed connective tissue (MCT) 60%

– Endocarditis 50%; chronic infections

– SLE 35%

– Sarcoidosis,

malignancy, lung disease

• High levels associated aggressive disease, joint erosions, worse prognosis

Question 3

Anti-CCP

1. Antibodies to citrullinated proteins
2. Anti‐cyclic citrullinated peptide (anti‐CCP)
3. in 70% of patients with early RA
4. More specificity characteristics of RA than RF (96% specificity; 78% sensitivity)
5. Anti CCP plus positive RF = 99.5% specificity for RA

Answer 3

Anti nuclear antibody (ANA)

Directed against nuclear antigens

Patterns of immunofluorescence of ANA

1. Homogenous pattern: histone antibody >95% drug induced lupus

• Rim pattern: anti DS DNA, 50% SLE
• Speckled:anti SM (Smith)– lupusanti SS‐A/SS‐B in Sjögren syndrome
• Anticentromere antibody in scleroderma CREST/PSS
• Anti scl 70‐PSS/CREST

Question 4

Criteria for SLE

• Malar rash

– Erythema, malar eminence spare nasolabial folds (butterfly rash)

• Discoid rash

– Erythematous patches

• Photosensitivity

– Rash due to sunlight

• Oral ulcers

– May include nasopharyngeal ulcers; usually painless

• Arthritis

– 2 or more peripheral joints, tender, swelling/effusion; non-erosive arthritis

• Serositis

– Pleuritis, rub or plerual effusion or pericarditis, ECG changes, rub or pericardia effusion

• Renal

Proteinuria > 500 mg/day or > 3+ or casts (either RBC, Hb, tubular, granular or mixed)

• Neurologic

–Seizures or psychosis

• Hematologic

–Hemolytic anemia with reticulocytosis or

–leukopenia (< 4000/mm3 total) or

–lymphopenia (< 1500/mm3 on 2 or more occasions) or

–thrombocytopenia (<100,000/mm3)

Answer 4

• Immunologic

–Anti‐DNA antibody titer or

–anti SM or

–antiphospholipid antibodies based on IgG or IgM cardiolipin antibodies or

–positive lupus anticoagulant or

–false positive RPR (test for syphilis)

–ANA – Abnormal titer

Question 5

Antistreptolysin O antibody (ASO titer) and anti DNAase B titers

• Evidence of a preceding group A streptococcal infection
• Elevated or rising titer
• Acute rheumatic fever (ARF) resulting from autoimmune reaction to infection with group A streptococci
• Strept may cause arthritis, often polyarticular and migratory/fever
• Often affects large joints (knees, hips, elbows, ankles) and is asymmetric
• May cause post‐streptococcal reactive arthritis; affects small joints (symmetric)

NOTE: Jones Criteria for Rheumatic Fever Carditis, Joint involvement (arthritis) Chorea, erythema marginatum, subcutaneous nodule Evidence of preceding strept infection

Question 6

hyperuricemia (uric acid > 6.8 mg/dl)

• Causes gouty arthritis
• Monosodium urate crystals in joint fluid or tophi
• Crystals are needle‐shaped, negative birefringent by polarized light microscopy
• Due to overproduction or under‐excretion of uric acid or both
• Acute onset, monoarticular, often 1st MTP joint (podagra). Often nocturnal awakening

• Can attack knees, feet, ankles

• Joints are hot, swollen, tender, dusky, red; fever

• Tophi – nodular deposits of monosodium urate crystals in skin

• 90% gout in men (4th‐6th decade)/post menopausal women

• Alcohol promotes increased urate production and decreased excretion

Answer 6

Treatment acute gout

• NSAIDS
• Colchicine – GI toxicity
• Steroids

Chronic management

– xanthine oxidase inhibitor

– uricouric drugs;

Probenecid ‐ block tubular resorption of urate and increased uric acid excretion

Question 7

Radiography

• Poor visualization of soft tissue
• (RA) symmetrical involvement of MCP, periarticular osteopenia (decreased bone mass, bone loss), erosions
• Plane radiographs may not detect early erosive arthritic disease

Answer 7

Ultrasonography

sensitive for soft tissue abnormalities (synovitis, tendonitis, bursitis) and erosions

• Aid in injecting/aspirating joint
• No radiation

Question 8

MRI -useful for soft tissue abnormalities

• Gadolinium contrast taken up in inflamed synovium (thickened pannus) IV gadolinium can cause nephrogenic systemic fibrosis (NSF) in patient with kidney disease
• Good for spine, SI, synovitis, tenosynovitis, erosions, joint inflammation

Answer 8

CT-best for bony abnormalities (trabecular, cortical bone), erosions, fractures, degenerative or inflammatory arthritis.

CT more sensitive than MRI for bone erosions

Question 9

Arthritis-Bowel

Inflammatory Bowel Disease

• Ulcerative Colitis
• Crohn’s Disease
• Behcet’s

Reactive Arthritis

• Bowel Infection

Answer 9

Arthritis-Pulmonary

• Clubbing ‐ HPO (hypertrophic pulmonary osteodystrophy)- intersitial lung disease
• Nodules ‐ R.A./W.G./Paraneoplastic
• Effusion – SLE/R.A.
• Hilar Nodes ‐ Sarcoid/R.A./Lymphoma
• Infiltrates – Septic/W.G.

Question 10

Arthritis-Endocrine

• Diabetes

‐ Charcot’s

‐ Cheiroarthropathy

• Thyroid

‐ Carpal/Tarsal Tunnel Syndrome

• Hyperparathyroidism

• Acromegaly

Answer 10

Arthritis-Ophthalmologic

• Retinopathy

– Cytoid Bodies

– Vasculitis