anti-nuclear antibody tests regan arendse fcp(sa), phd rheumatologist saskatoon

Anti-Nuclear Antibody Tests

Regan Arendse FCP(SA), PhDRheumatologist

Saskatoon

Case study

Questions

• Is the ANA a useful clinical tool?• What causes a false positive ANA?• When should an ANA test be requested?

Rates of positive ANA in healthy and ill

Negative ANAPositive ANAANA with disease

Wandstrat et al., J Autoimmun 2006; 27: 153-60

Gender and positive ANA

Healthy controls (n=18) SLE (n=14)0

10

20

30

40

50

60

70

80

90

100

FemalesMales

Quan-Zhen et al., Arth Res Ther 2011

Age and positive ANA

• No association between age (20-60 years) and ANA positivity

Tan et al., Arth & Rheum 1997; 40: 1601-11

Quan-Zhen et al., Arth Res Ther 2011

Accumulated % + antibodies over 10 years before diagnosis with SLE

-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 diagnosis 0

10

20

30

40

50

60

70

80

90

100

ANAdsDNARNPSSA

Erikson et al., Arth Res Ther 2011; 13

Antibody presence predating disease

arthritis skin serositis other0

1

2

3

4

5

6

7

8

Erikson et al., Arth Res Ther 2011; 13

Predictive value of ANA for SLE

• Incidence rate of SLE, lupus develops in <1% positive ANA individuals

• None of 24 ANA asymptomatic children developed disease over mean 61 month follow up period

• Predictive value of ANA increases in the at risk population with clinical disease

Aho et al., J Rheum 1992; 19: 1377-9

Cabral et al., Pediatrics 1992; 89: 441-4

Answer

• The ANA is not a good screening tool for auto-immune disease in the absence of convincing clinical signs

• Long time interval between ANA positivity and onset of disease does not warrant screening

• Lack of any effective pre-emptive or prophylactic treatment emphasizes that the argument not to routinely request an ANA

What causes a false positive ANA?

HEp-2 indirect immunofluorescence

Antigens with similar structure to pathologic antigens

• Viruses (Herpes viruses and HIV)• Drugs which alter proteins (Procainamide,

INH, Phenytoin)• Malignant cells• Environmental toxins (silicone)

When should an ANA test be requested?

• Yes if strong clinical suspicion of autoimmune disease

• Scleroderma• Lupus• Dermatomyositis• Sjogren’s disease• Mixed connective tissue disease

When should an ANA test be requested?

• No if not a strong clinical suspicion of autoimmune disease

• Chronic pain• Chronic fatigue • Chilblains • Raynaud’s phenomenon• Rosacea

When should an ANA test be requested?

• 8.8% of fibromyalgia patients have +ANA• 8.9% of controls have +ANA• In prospective study over 4 years, in 12 with

FMS and 12 controls, one in FMS group developed SLE and one in controls developed Sjogren’s syndrome

Al Allaf et al., Clin Rheuma 2002; 21: 472-7

Conclusion

• ANA should not be routinely requested• ANA should not be requested for non-specific

symptoms• ANA should only be requested in patients with

clinical features strongly suggestive of an auto-immune disease

• Causes of false positives are many and varied