What conditions, other than Rheumatoid Arthritis (RA), can have a positive Rheumatoid Factor (RF)?

Conditions with Positive Rheumatoid Factor Other Than RA

Rheumatoid factor (RF) positivity occurs in multiple autoimmune, infectious, and inflammatory conditions beyond rheumatoid arthritis, with systemic lupus erythematosus, Sjögren's syndrome, bronchiectasis, vasculitis, and cancer immunotherapy-related arthritis being the most clinically significant.

Autoimmune and Connective Tissue Diseases

Systemic Lupus Erythematosus (SLE)

• RF is present in 17.9% to 24.9% of SLE patients, making it a common finding in this population 1, 2
• RF-positive SLE patients demonstrate a distinct clinical profile with higher prevalence of anti-Ro/SS-A antibodies, butterfly rash, and hypothyroidism 1
• Importantly, RF positivity in SLE is associated with protection from glomerulonephritis (OR = 0.45), suggesting a less severe renal disease phenotype 1
• IgA RF specifically correlates with sicca syndrome, hypergammaglobulinemia, elevated ESR, leukopenia, and SSA/SSB antibodies in SLE patients 2
• RF-positive SLE patients may have relative immune competence and are less likely to require high-dose steroids or cytotoxic drugs 3

Sjögren's Syndrome

• RF positivity occurs in checkpoint inhibitor-induced sicca syndrome, though at lower rates (9% RF positive) compared to classical Sjögren's syndrome 4
• RF is associated with sicca syndrome, SSA-antibodies, and SSB-antibodies in autoimmune contexts 2

Pulmonary Conditions

Bronchiectasis

• RF is more prevalent in patients with bronchiectasis compared to healthy controls, particularly in those with underlying rheumatoid arthritis 4
• Rheumatoid arthritis accounts for 2-5% of bronchiectasis cases, and RF testing is part of the aetiological workup 4
• However, anti-CCP antibodies are strongly positive in only 12% of RF-positive bronchiectasis patients, with only half subsequently developing RA 4

Vasculitis and Inflammatory Conditions

Checkpoint Inhibitor-Related Vasculitis

• All vessel-sized vasculitis (large, medium, and small vessels) can occur with cancer immunotherapy, though RF is rarely positive in these cases 4
• When present, RF levels range from 18-246 IU/mL in checkpoint inhibitor-induced arthritis 4
• Cryoglobulin and RF were rarely positive in vasculitis associated with checkpoint inhibitors 4

Important Clinical Considerations

RF Isotypes and Disease Activity

• IgA RF may be a more specific predictor of disease severity than IgM RF or IgG RF in inflammatory conditions 5
• IgA RF shows closer association with overall disease activity, articular index, grip strength, and ESR compared to IgM RF 5
• IgA RF is associated with severity of erosive arthritis across multiple studies 5

Non-Specific RF Positivity

• RF positivity is widely observed in patients with advanced age, infectious diseases, autoimmune diseases, and lymphoproliferative diseases 6
• Among 230 RF-positive patients in a rheumatology clinic, RA was the most common diagnosis (62.2%), but many other conditions were represented 6
• RF levels between 20-50 IU/mL had significantly lower rates of rheumatic disease diagnosis compared to higher titers 6

Critical Diagnostic Pitfalls

• RF alone cannot predict rheumatological disease, and there is no significant relationship between RF levels and anti-CCP positivity in many cases 6
• Negative RF does not exclude RA, as seronegative RA accounts for 20-30% of cases 7
• RF should always be interpreted alongside clinical findings, anti-CCP status, and other laboratory tests 8
• Do not dismiss other diagnoses based solely on RF positivity, as it can be found asymptomatically in the general population 6