Anti-Nuclear Antibody Tests Regan Arendse FCP(SA), PhD Rheumatologist 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 Wandstrat et al., J Autoimmun 2006; 27: 153-60

Gender and positive ANA Quan-Zhen et al., Arth Res Ther 2011

Age and positive ANA No association between age (20-60 years) and ANA positivity Quan-Zhen et al., Arth Res Ther 2011 Tan et al., Arth & Rheum 1997; 40: 1601-11

Accumulated % + antibodies over 10 years before diagnosis with SLE Erikson et al., Arth Res Ther 2011; 13

Antibody presence predating disease 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