What autoimmune conditions should be screened for in a patient with uveitis, particularly those with a possible history of injection drug use?

Autoimmune Screening for Uveitis

Screen for sarcoidosis, HLA-B27-associated spondyloarthropathies, juvenile idiopathic arthritis (in children), and syphilis as the core autoimmune and infectious workup for uveitis, with additional testing guided by anatomic location and clinical presentation.

Essential Screening for All Uveitis Patients

• Syphilis serology is mandatory in all forms of uveitis, regardless of anatomic location or clinical presentation 1
• This is non-negotiable given syphilis can mimic virtually any uveitis pattern and requires specific antimicrobial therapy

Anatomically-Guided Autoimmune Screening

Anterior Uveitis (Unilateral, Acute, Non-Granulomatous)

• HLA-B27 testing is the primary autoimmune screen for unilateral acute anterior non-granulomatous uveitis 1
• HLA-B27 positivity indicates seronegative spondyloarthritis association 2, 3
• Refer to rheumatology if inflammatory back pain, morning stiffness, or family history of spondyloarthritis is present 3

Chronic or Bilateral Uveitis

• Serum angiotensin-converting enzyme (ACE) level to screen for sarcoidosis 1
• Interferon-gamma release assay (IGRA) to exclude tuberculosis before initiating immunosuppression 3, 1
• Chest computed tomography for pulmonary sarcoidosis or tuberculosis 1
• Sarcoidosis presents with mutton-fat keratic precipitates, iris nodules, and can cause sight-threatening cystoid macular edema 4

Intermediate or Posterior Uveitis (Age >40 Years)

• Cerebral MRI and anterior chamber tap with interleukin-10 analysis to exclude masquerade syndromes, particularly primary CNS lymphoma 1
• Masquerade syndromes occur in up to 2.5% of noninfectious uveitis cases in tertiary centers and require diagnostic vitrectomy, CSF cytology, and brain MRI 2

Pediatric-Specific Screening

• Screen children with juvenile idiopathic arthritis (JIA) for uveitis every 3 months if at high risk 5
• JIA-associated uveitis develops in 10-20% of children with JIA and is typically asymptomatic 5
• Early detection through regular screening prevents vision-threatening complications in 25-50% of cases 5

Special Populations: Injection Drug Use Context

Given the expanded question mentions possible injection drug use history:

• HIV serology is essential before initiating systemic immunosuppression 3
• Hepatitis B and C screening is required before starting immunomodulatory therapy 3
• Blood cultures and intraocular fluid sampling if endogenous endophthalmitis is suspected, particularly in patients with systemic sepsis or indwelling catheters 2
• Infectious causes must be excluded through sampling and culturing of intraocular fluids in immunosuppressed patients 2

Additional Rare Autoimmune Associations

• Tubulointerstitial nephritis and uveitis (TINU) syndrome: Check urinalysis, serum creatinine, and consider renal biopsy if acute kidney injury is present 6
• Autoimmune lymphoproliferative syndrome (ALPS): Consider in patients with recurrent uveitis and lymphoproliferation 7

Critical Pitfalls to Avoid

• Do not pursue extensive autoimmune panels without clinical orientation - investigations prescribed without anatomic or clinical guidance are usually unhelpful 1
• Always exclude infection before diagnosing autoimmune uveitis, especially in immunosuppressed patients or those with atypical presentations 2, 3
• Granulomatous uveitis with HLA-B27 positivity should raise concern for misdiagnosis or masquerade syndrome and requires immediate diagnostic reassessment 3