The ANA Test: All You Need to Know Department of Family and Community Medicine Family Medicine Update April 25, 2014

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1 The ANA Test: All You Need to Know Department of Family and Community Medicine Family Medicine Update April 25, 2014 Celso R. Velázquez MD Division of Rheumatology University of Missouri Antinuclear antibodies (ANA) Diverse antibodies directed against nuclear components and are the hallmark of autoimmune diseases. May be detected by ELISA ( 180 units ) Immunoflourescence ( 1:1280 ) Immunoflourescence is better. 1

2 ANA by ELISA ANA by immunofluorescence (IF) Called FANA at Mizzou. Result is a titer ( 1:160 is significant) and a pattern. More accurate than the ELISA 2

3 Antinuclear antibodies Positive in 98% of patients with lupus Titers start at 1:40 and go up to 1:5160. Titers 1:160 are considered positive. In general, higher titers are more specific but the ANA titer does not correlate with the severity of the disease. ANA in healthy persons Titers 1:160 may be found in 5% of the population, and titers 1:320 may be seen in 3% of the population 3

4 ANA patterns on IF Centromere pattern: limited scleroderma (CREST) Nucleolar pattern: usually correlates with diffuse scleroderma. Speckled pattern: usually correlates with Sjögren syndrome. These have been replaced by the ANA panel. The ANA panel: the auto antibodies are more specific but less sensitive. Anti DNA antibodies: quite specific for lupus and are a useful marker of disease activity. Many other specific antibodies: Anti Sm: associated with lupus Anti SSA (Ro) and SSB (La): associated with Sjögren syndrome Anti RNP: associated with mixed connective tissue disease Anti Scl 70: associated with scleroderma 4

5 The ANA panel: not a good screening test. Conditions associated with ANA Rheumatic diseases Systemic lupus erythematosus (SLE): 98% Discoid lupus: 15% Scleroderma: 85% Polymyositis and dermatomyositis: 61% Sjögren syndrome: 48% Rheumatoid arthritis: 41% Juvenile rheumatoid arthritis: 71% 5

6 Conditions associated with ANA (2) Other autoimmune diseases Autoimmune thyroid disease (Graves and Hashimoto s) Autoimmune hepatitis Primary biliary cirrhosis Multiple sclerosis Other conditions Drug induced lupus Drug induced ANA Chronic infections (hepatitis C, HIV) Lymphoproliferative disorders 6

7 So, when should we order an ANA? To establish a diagnosis in patients with features suggestive of a connective tissue disease To exclude connective tissue diseases in patients with few findings To monitor disease activity (anti DNA) A young woman with polyarthritis and a rash Patients with SLE often also have fever, serositis, cytopenias. Also order: CBC, creatinine, UA 7

8 SLE: revised criteria A woman with Raynaud phenomenon Raynaud phenomenon (RP) is seen in up to 5% of the population and may be primary or secondary. A negative ANA test suggests primary RP. 8

9 A 63 year old woman with dry eyes and dry mouth. The prevalence of Sjögren syndrome (SjSd) is up to 2% of the population. Up to 50% of patients with SjSd may have a negative ANA. A rheumatoid factor may be positive in these patients. Other scenarios: A child with polyarthritis juvenile rheumatoid arthritis A man with fever, arthritis and pleurisy after taking hydralazine drug induced lupus A man with proximal muscle weakness (but not much pain) polymyositis 9

10 The ANA test if not very useful in: The patient with widespread pain and no other organ system involvement. The ANA test if not very useful in: The patient with polyarthritis that is characteristic of rheumatoid arthritis. 10

11 The ANA test if not very useful in: The patient with joint pain that is characteristic of osteoarthritis. ANA testing in the outpatient setting 11

12 ANA testing in the outpatient setting What do you do if the ANA is negative? What kind of assay did you order? Consider disease that can look like SLE: Sjögren syndrome Antiphospholipid syndrome Vasculitis The ANA is occasionally negative in patients with SLE in remission or with end stage renal disease. 12

13 What do you do if the ANA is positive ( 1:160) but a low titer? (And your rheumatologist says it s not lupus ) When we say the patient does not have lupus we mean that the patient does not have lupus right now. Up to 30% of patients referred to a rheumatology clinic for evaluation of a positive ANA develop lupus upon follow up. The risk, however, is low and around 5% in 10 years for persons with ANA 1:320. Serial exams and CBC and UA are indicated in some patients. Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus 115/130 patients with SLE had autoantibodies a mean of 3.3 years before diagnosis of SLE. 13

14 The ANA Test: All You Need to Know (hopefully) Thank you. Celso R. Velázquez MD Division of Rheumatology University of Missouri 14

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