What are the causes of bilateral granulomatous uveitis?

Bilateral Granulomatous Uveitis: Causes

Sarcoidosis is the most important noninfectious cause of bilateral granulomatous uveitis to consider, while tuberculosis and syphilis represent critical infectious etiologies that must be ruled out to prevent vision loss. 1, 2, 3

Infectious Causes

Bacterial Infections

• Tuberculosis (Mycobacterium tuberculosis) is a major cause of bilateral granulomatous uveitis, particularly in endemic regions, and can present with interstitial keratitis and anterior uveitis 3, 4
• Syphilis (Treponema pallidum) causes infectious retinal vasculitis and granulomatous inflammation, requiring prompt serologic testing 2, 3
• Post-streptococcal syndrome can manifest as acute bilateral granulomatous uveitis with associated reactive arthritis, particularly in children with elevated anti-streptolysin O titers 5

Viral Infections

• Herpes simplex virus (HSV) and varicella-zoster virus (VZV) produce retinal vasculitis with immunologically mediated infiltrates and can cause granulomatous inflammation 2, 3, 6
• Cytomegalovirus (CMV) represents an important cause in immunocompromised patients, particularly those with AIDS 3, 6
• Hepatitis A virus (HAV) has been reported as a rare cause of acute bilateral granulomatous anterior uveitis through immune-complex deposition mechanisms 7
• Epstein-Barr virus may produce retinal vasculitis and uveitis 2, 3

Parasitic Infections

• Toxoplasmosis (Toxoplasma gondii) is the most common parasitic cause of retinal vasculitis and retinochoroiditis, representing the most frequent infectious cause of retinitis overall 2, 3, 6
• Onchocerca volvulus can involve the uvea and retina, particularly in endemic areas 2, 3

Fungal Infections

• Candida species cause endogenous endophthalmitis through hematogenous spread during candidemia, requiring dilated retinal examination within the first week of therapy 3, 6

Noninfectious/Autoimmune Causes

Systemic Vasculitides

• Sarcoidosis represents the major systemic inflammatory condition associated with bilateral granulomatous uveitis, with bimodal age presentation (highest incidence between ages 20-39), featuring conjunctival nodules, iris nodules, trabecular meshwork nodules, choroidal granulomas, and vitreous opacities 1, 2, 6
• Granulomatosis with polyangiitis produces retinal vasculitis, necrotizing scleritis, peripheral ulcerative keratitis, and optic disc swelling as part of systemic manifestations 1, 2, 6
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is associated with retinal vasculitis and granulomatous inflammation 1, 2

Autoimmune Diseases

• Vogt-Koyanagi-Harada (VKH) disease presents with rapid onset bilateral granulomatous anterior uveitis (95% bilateral), vitritis, optic disc edema, cystoid outer retinal fluid, and numerous central leakage points on fluorescein angiography, typically in young patients 1, 8
• Systemic lupus erythematosus is a well-established cause of retinal vasculitis and should be considered in the differential diagnosis 2, 6
• HLA-B27-associated conditions (ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease) are associated with granulomatous uveitis 3
• Juvenile idiopathic arthritis is a significant cause in children requiring prompt diagnosis and treatment 3

Other Inflammatory Conditions

• Posterior scleritis presents in middle-aged women with deep pain, choroidal folds, serous retinal detachment, and fluid in the sub-Tenon space (T-sign on ultrasonography) 1
• Relapsing polychondritis may produce retinal vasculitis and granulomatous inflammation 1, 2

Drug-Induced Causes

• Methamphetamine, intravenous immunoglobulins, opioids, hydralazine, antifibrotics, antibiotics, and leukotrienes can all cause drug-induced vasculitis affecting retinal vessels and producing granulomatous inflammation 1, 2

Critical Diagnostic Considerations

Emergent Exclusions

• Giant cell arteritis (GCA) represents an ophthalmologic emergency that must be excluded promptly in patients over 50 years with appropriate clinical context, as it can cause central retinal artery occlusion 2

High-Risk Populations

• Patients with AIDS, prolonged hospitalization, indwelling catheters, and systemic immunosuppression are at higher risk for infectious causes, particularly CMV and Candida 6
• Screening for latent or active tuberculosis is essential before starting systemic immunomodulatory therapy 3

Common Pitfalls

• Approximately half of anterior uveitis cases remain idiopathic despite thorough workup, but infectious etiologies must be ruled out first as they are vision-threatening 7, 9
• Air travel, immigration, and globalization have changed traditional geographic distribution patterns of infectious diseases; consider emerging infectious diseases including Rickettsioses, West Nile virus, Rift Valley fever, dengue fever, and chikungunya in appropriate epidemiological contexts 9