Laboratory tests in rheumatology: A rational approach

Ernest Suresh

doi:10.3949/ccjm.86a.18076

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TABLE 1

Conditions associated with rheumatoid factor

Condition	Frequency
Rheumatoid arthritis	70%
Other autoimmune rheumatic conditions
Primary Sjögren syndrome	75%–95%
Systemic lupus erythematosus	15%–35%
Systemic sclerosis	20%–35%
Systemic vasculitis	5%–20%
Infections^a
Infective endocarditis	40%
Syphilis	8%–37%
Hepatitis B	25%
Hepatitis C	76%
Human immunodeficiency virus infection	10%–20%
Tuberculosis	15%
Other diseases
Liver cirrhosis	25%
Mixed cryoglobulinemia	100%
Primary biliary cirrhosis	45%–70%
Healthy people	5%–25%^b

↵a The rheumatoid factor in infectious diseases is produced by B cells, possibly to clear the immune complexes. They are usually transient and harmless.
↵b The frequency rises with age (5% at age 50, rising to 10% to 25% at age 70.
Data from reference 3.

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TABLE 2

Clinical and laboratory manifestations of systemic lupus erythematosus

Pathogenesis	Examples of disease manifestations
Nonspecific inflammatory response	Fever, fatigue, arthralgia, weight loss, anemia of chronic disease, elevated erythrocyte sedimentation rate
Immune complex deposition (commonly in the synovium, skin, serosa, kidneys, and lungs)	Inflammatory arthritis, photosensitive skin rashes, pleurisy, pericarditis, glomerulonephritis, pneumonitis, or interstitial lung disease
Direct antibody-mediated attack	Hemolytic anemia (red cell antibodies), thrombocytopenia (antiplatelet antibodies), lymphopenia (lymphocytotoxic antibodies), neuropsychiatric manifestations such as depression and psychosis (antiribosomal P antibodies)
Associated features	Recurrent thrombosis and miscarriages (antiphospholipid syndrome), dry eyes and mouth (Sjögren syndrome)
Laboratory clues	Hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, normal C-reactive protein, low complement (due to immune complex formation), and abnormal urinalysis (proteinuria, hematuria, red cell casts, or dysmorphic red cells)

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TABLE 3

Disease associations of specific antigen targets

Antigen target	Disease association
Double-stranded DNA and Sm	Systemic lupus erythematosus
Ro and La	Sjögren syndrome; Ro also associated with subacute cutaneous lupus
U1-RNP	Mixed connective tissue disease
Jo-1	Polymyositis (higher risk of interstitial lung disease)
ScL-70	Diffuse cutaneous scleroderma
Anticentromere	Limited cutaneous scleroderma

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TABLE 4

Some indications to test for antiphospholipid antibodies^a

Unprovoked deep vein thrombosis or pulmonary embolism
(Antiphospholipid antibody testing is not recommended in patients with provoked venous thrombosis, as there is insufficient evidence to recommend long-term anticoagulation.)

Ischemic stroke (including transient ischemic attack) in patients under age 50

Patients with both arterial and venous events

Recurrent thrombosis

Thrombosis in an unusual site

Pregnancy morbidity
(1 or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation; 1 or more premature births of a morphologically normal neonate before the 34th week of gestation because of preeclampsia, eclampsia, or placental insufficiency; or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation)

All patients with systemic lupus erythematosus

↵a Knowledge of the antiphospholipid antibody status helps to decide if low-dose aspirin should be recommended for primary prevention of thrombosis.³² Lupus anticoagulant is likely to be falsely positive in those with acute thrombosis and those receiving anticoagulant therapy. Hence, anticoagulant therapy should be interrupted for at least 7 days before testing for lupus anticoagulant. However, anticardiolipin and anti-beta-2 glycoprotein I can be tested at any time, as they are not affected by thrombosis or anticoagulant therapy.

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TABLE 5

Clinical indications to test for antineutrophil cytoplasmic antibody

Glomerulonephritis

Pulmonary hemorrhage (especially with pulmonary-renal syndrome)

Multiple lung nodules

Mononeuritis multiplex or unexplained peripheral neuropathy

Cutaneous vasculitis, especially with systemic features

Scleritis

Retroorbital mass

Chronic destructive disease of the upper airways

Chronic sinusitis or otitis

Subglottic tracheal stenosis

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TABLE 6

Conditions associated with antineutrophil cytoplasmic antibody (ANCA) other than ANCA-associated vasculitis

Gastrointestinal disorders
Inflammatory bowel disease
Primary sclerosing cholangitis
Primary biliary cirrhosis
Autoimmune hepatitis
Viral hepatitis

Infections
Infective endocarditis
Tuberculosis
Malaria

Drugs
Propylthiouracil
Minocycline
Hydralazine
Allopurinol
Levamisole

Autoimmune diseases
Rheumatoid arthritis
Systemic lupus erythematosus (SLE)^a
Antiglomerular basement membrane disease

↵a Antinuclear antibody (ANA) and p-ANCA resemble each other closely and are difficult to differentiate. Thus, SLE sera may show positive p-ANCA staining due to presence of ANA.