Association Between Wagner's Granulomatosis and Rheumatoid Arthritis
Wagner's granulomatosis (now known as granulomatosis with polyangiitis, GPA) is not typically associated with rheumatoid arthritis (RA), but rare cases of co-occurrence have been documented in the medical literature.
Understanding the Relationship
Wagner's granulomatosis (GPA) is a distinct systemic vasculitis characterized by:
- Necrotizing granulomatous vasculitis of the upper and lower respiratory tract
- Glomerulonephritis
- Small-vessel vasculitis involving arteries and veins 1
While GPA and RA are generally considered separate autoimmune conditions, there is evidence of rare overlap:
- Case reports document patients who develop both conditions
- Most commonly, RA precedes the development of GPA 2, 3
- The co-existence is predominantly observed in female patients 3
Epidemiological Evidence
The literature review of co-existing RA and GPA cases reveals:
- In a 2003 study, all documented cases were female patients 3
- The mean age at RA onset was approximately 43.7 years 3
- The average interval between RA diagnosis and subsequent GPA diagnosis was about 8 years (101 months) 2
- All patients with both conditions had positive rheumatoid factor 3
Genetic Considerations
Some genetic factors may contribute to the rare overlap:
- A functionally relevant IRF5 haplotype has been associated with reduced risk of GPA, similar to protective effects seen in RA and SLE 4
- This suggests some shared genetic risk factors between these autoimmune conditions, though they remain distinct disorders
Clinical Implications
When a patient has RA and develops symptoms suggestive of GPA:
- Upper respiratory involvement (present in 83% of overlap cases) 3
- Lower respiratory signs (67% of overlap cases) 3
- Renal involvement (33% of overlap cases) 3
- Positive ANCA, particularly PR3-ANCA (67% of tested cases) 3
Treatment Considerations
For patients with both conditions:
- Cyclophosphamide and corticosteroids have been the mainstay of treatment for most documented cases 2
- Rituximab is FDA-approved for both GPA and RA and may be considered 5
- TNF inhibitors used for RA require caution, as there are case reports suggesting they might potentially trigger or exacerbate vasculitis in some patients 6
Important Caveats
- The association between GPA and RA is rare but should be considered in the differential diagnosis when vasculitis develops in patients with RA 2
- Most recent evidence suggests that when both conditions co-exist, they represent true disease overlap rather than a single pathological process 2, 6
- Careful monitoring for vasculitis symptoms is warranted in RA patients, particularly those on biologic therapies
Conclusion
While GPA and RA share some clinical features (vasculitis, ocular inflammation, interstitial lung disease, and arthritis), they are generally distinct conditions with different pathophysiological mechanisms. The co-occurrence is uncommon but documented, and clinicians should maintain vigilance for the development of GPA in patients with established RA, especially when new respiratory, renal, or systemic vasculitic symptoms emerge.