What conditions can cause false positive Rheumatoid Factor (RF) test results?

False Positive Rheumatoid Factor Conditions

Rheumatoid factor (RF) positivity occurs in numerous non-rheumatoid arthritis conditions, with the most common false positives arising from other autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus), chronic infections (hepatitis C, endocarditis, mononucleosis), and healthy elderly individuals, making RF a highly non-specific test that should never be interpreted in isolation. 1, 2, 3

Autoimmune and Connective Tissue Diseases

Primary causes of false positive RF:

• Sjögren's syndrome is a major cause of RF positivity, with RF present in checkpoint inhibitor-induced sicca syndrome (9% RF positive) and classical Sjögren's syndrome at higher rates 1
• Systemic lupus erythematosus (SLE) frequently demonstrates RF positivity, with patients having positive ANA being significantly more likely to receive an erroneous prior diagnosis based on RF results (128/146 with SLE diagnosis had positive ANA, P = 8.77E-06) 4
• Systemic sclerosis (scleroderma) can present with positive RF 2, 3
• Mixed connective tissue disease shows RF positivity 3
• Dermatomyositis and polymyositis may have positive RF 3

Infectious Diseases

Chronic and acute infections commonly cause transient or persistent RF elevation:

• Mononucleosis (Epstein-Barr virus) produces false positive RF results 2
• Cytomegalovirus infection causes RF positivity 2
• Parvovirus infection can elevate RF 2
• Hepatitis C is associated with RF positivity, particularly in the context of cryoglobulinemia 5
• Bacterial endocarditis can produce positive RF 3

Pulmonary Conditions

Chronic lung diseases show increased RF prevalence:

• Bronchiectasis demonstrates higher RF prevalence compared to healthy controls, with rheumatoid arthritis accounting for 2-5% of bronchiectasis cases 1
• Among RF-positive bronchiectasis patients, anti-CCP antibodies are strongly positive in only 12%, with only half subsequently developing rheumatoid arthritis 1

Vasculitis

Various vessel-sized vasculitides can show RF positivity:

• Large, medium, and small vessel vasculitis associated with checkpoint inhibitor therapy can occur, though RF is rarely positive in these cases (range 18-246 IU/mL when present) 1, 2
• Cryoglobulin and RF were rarely positive in vasculitis associated with checkpoint inhibitors 1

Age-Related False Positives

Elderly populations have higher baseline RF positivity:

• The incidence of false-positive RFs among elderly patients (69%) was not significantly higher than among younger patients (65%), though older age was associated with previous RA diagnosis (P = 5.89E-06) 6, 4
• RF positivity can occur in healthy individuals without any rheumatic disease 7, 6

Critical Diagnostic Performance Data

Understanding RF test limitations is essential:

• In a comprehensive analysis, RF sensitivity for rheumatoid arthritis was only 0.28 with specificity of 0.87 6
• The positive predictive value for rheumatoid arthritis was only 0.24, meaning 76% of positive RF results were false positives 6
• The positive predictive value for any rheumatic disease was 0.34, indicating 66% false positive rate 6
• Among 524 patients with previous diagnosis of RA, SLE, or SSc, the diagnosis was excluded in 394 (75.2%) subjects upon proper evaluation 4

Clinical Pitfalls to Avoid

Common errors in RF interpretation:

• Never order RF as a screening test in low pretest probability patients, as the majority of positive results will be false positives with a cost per true-positive RF result of $563 6
• Always correlate with anti-CCP antibodies, which are more specific for rheumatoid arthritis (anti-CCP strongly positive in only 12% of RF-positive bronchiectasis patients) 1
• RF positivity alone does not make a diagnosis and absence does not exclude disease 7, 3
• False positive results may lead to wrong treatment and unnecessary anxiety for patients 7
• The diagnostic utility of RF may be greatest when it is negative (negative predictive value 0.89 for RA), though seronegative rheumatic disease still occurs 6

Proper Diagnostic Approach

Algorithm for RF interpretation:

• Order RF only when pretest probability of rheumatoid arthritis is high based on clinical findings (symmetric polyarthritis, morning stiffness >30 minutes, involvement of small joints) 3, 6
• If RF positive, always order anti-CCP antibodies for confirmation, as anti-CCP has higher specificity 3
• Evaluate for alternative diagnoses listed above, particularly if anti-CCP is negative 1, 2
• Consider that RF values should be categorized as negative (≤ULN, typically ≤14-15 IU/mL), low positive (>ULN but ≤3 times ULN), or high positive (>3 times ULN), with higher values more specific for RA 2
• In the 2010 ACR/EULAR classification criteria, RF contributes 0 points if negative, 2 points if low positive, and 3 points if high positive, requiring ≥6/10 total points for RA classification 2, 5