Causes of Uveitis
Uveitis is typically due to autoimmune conditions or is idiopathic, with only infrequent cases caused by infection 1.
Primary Etiologic Categories
The causes of uveitis can be systematically organized into three main categories:
1. Non-Infectious Causes (Most Common)
Idiopathic/Undifferentiated: Represents 27-51% of cases in the US and Europe 2, and up to 42% in recent meta-analyses 3
Autoimmune/Systemic Disease-Associated (37-49% of cases) 2:
- HLA-B27-associated acute anterior uveitis (5.7% of cases) 4 - the leading identifiable cause in Western countries, particularly associated with spondyloarthritis 5
- Sarcoidosis (4.98-6.1% of cases) 4, 3 - underestimated cause with predilection for middle-aged women 5
- Ankylosing spondylitis (3.6%) 4
- Multiple sclerosis (4.7%) 4
- Juvenile idiopathic arthritis - particularly in children with oligoarticular onset 6
- Connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus)
- Vasculitic disorders (polyarteritis nodosa, granulomatosis with polyangiitis)
- Behçet's disease 7
Ocular-Specific Syndromes (31.8%) 4:
2. Infectious Causes (11-21% in High-Income Countries; 50% in Low-Middle Income Countries) 2
When infection occurs, it is almost always caused by endogenous microbes accessing the eye via a breach in the blood-eye barrier 1.
Key infectious agents include 1:
Parasitic:
Viral:
Bacterial:
3. Drug-Induced Uveitis
An increasingly recognized category, particularly with newer biologic therapies 9:
- Immune checkpoint inhibitors (ICPIs) - strongly associated with uveitis 9
- BRAF and MEK inhibitors 9
- Anti-VEGF agents 9
- TNF-α inhibitors (paradoxically can cause uveitis despite treating it) 9
- Bisphosphonates - strongly associated, particularly in patients with known inflammatory joint disease 9, 5
- Topical prostaglandin analogues 9
- Topical brimonidine 9
- Cidofovir 9
- BCG vaccination 9
Important Clinical Considerations
Risk Factors That Influence Etiology:
- Immunosuppression: Increases risk of infectious causes (Toxoplasma, herpes viruses) 5
- Geographic location: Affects prevalence of specific infectious agents
- Genetic factors: HLA-B27 strongly associated with anterior uveitis and spondyloarthritis 2
- Age: Juvenile idiopathic arthritis-associated uveitis peaks at ages 1-5 years 6
Critical Pitfalls to Avoid:
- Do not dismiss infection in immunosuppressed patients - even when on treatment for presumed autoimmune disease 5
- Always obtain thorough medication history - drug-induced uveitis is often overlooked and can avoid expensive unnecessary testing 9
- Consider syphilis and tuberculosis - these treatable infections must be ruled out in the diagnostic workup 1, 5
- Recognize masquerade syndromes - malignancy (especially lymphoma) can mimic uveitis and represents up to 2.5% of cases at tertiary centers 10
Diagnostic Approach:
The etiology should be pursued based on anatomic location (anterior, intermediate, posterior, or panuveitis), clinical presentation, and associated systemic symptoms 1. In patients with known chronic inflammatory joint disease presenting with uveitis, consider bisphosphonate therapy and immunosuppression-related infections first 5. For patients with inflammatory or non-inflammatory back pain and uveitis, evaluate for spondyloarthritis, as two-thirds of these patients have their joint disease diagnosed during uveitis evaluation 5.