# Anterior Uveitis: HLA-B27 Disease, Sarcoidosis, and Herpetic Uveitis

## Introduction

**Anterior uveitis** is the most common form of uveitis, accounting for 50-60% of all cases. While many cases are idiopathic, three important etiologic categories -- **HLA-B27-associated disease**, **sarcoidosis**, and **herpetic uveitis** -- are frequently encountered and require distinct diagnostic and therapeutic approaches.

## HLA-B27-Associated Anterior Uveitis

### Epidemiology

Most common identifiable cause of acute anterior uveitis. HLA-B27 prevalence: 6-8% of general population; present in 50% of acute anterior uveitis patients. Male predominance; peak age 20-40 years. **Associated spondyloarthropathies**: ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, inflammatory bowel disease (IBD)-related arthritis.

### Clinical Features

**Acute onset**, unilateral (may alternate sides between episodes), **recurrent**. Marked anterior chamber reaction with **fibrin** formation. **Hypopyon** -- may be present; non-infectious, sterile. Fine to medium keratic precipitates (non-granulomatous) **Posterior synechiae** -- common; may form rapidly. Rarely associated with intermediate or posterior uveitis.

Typically self-limited episodes lasting 6-12 weeks.

### Systemic Associations

**Ankylosing spondylitis** -- inflammatory low back pain, sacroiliitis; most common systemic association. **Reactive arthritis** (formerly Reiter syndrome) -- urethritis, conjunctivitis, arthritis; post-infectious. **Psoriatic arthritis** -- skin and nail changes. **IBD-associated arthritis** -- Crohn disease or ulcerative colitis.

### Workup

**HLA-B27 testing** -- confirmatory; not diagnostic alone. **Sacroiliac joint X-ray or MRI** -- if back pain present. **ESR/CRP** -- systemic inflammation markers. Rheumatology referral for suspected spondyloarthropathy.

### Treatment

**Topical corticosteroids** -- prednisolone acetate 1% hourly initially, with rapid taper. **Cycloplegic/mydriatic agents** -- cyclopentolate 1% or atropine 1% to prevent/break synechiae. **Periocular or systemic corticosteroids** -- for severe or refractory cases. **TNF-alpha inhibitors** (adalimumab, infliximab) -- for frequent recurrences; reduce flare rate significantly.

![Slit-lamp photograph showing fibrin membrane and hypopyon in HLA-B27 acute anterior uveitis](/images/ophthalmology/hla-b27-hypopyon-fibrin.jpg)

## Anterior Uveitis Differential Comparison

| Feature | HLA-B27 | Sarcoidosis | Herpetic (HSV/VZV) |
|---------|---------|-------------|---------------------|
| Onset | Acute | Acute or chronic | Acute |
| Laterality | Unilateral (alternating) | Bilateral | Unilateral |
| Pattern | Recurrent, self-limited (6-12 wk) | Chronic or recurrent | Recurrent |
| KP type | Fine-medium (non-granulomatous) | Mutton-fat (granulomatous) | Stellate or fine |
| Key signs | Fibrin, hypopyon, posterior synechiae | Iris nodules (Koeppe/Busacca), snowballs | Sector iris atrophy, elevated IOP |
| IOP | Normal or low | Variable | Often elevated (trabeculitis) |
| Systemic associations | AS, reactive arthritis, psoriasis, IBD | Pulmonary, skin, CNS, parotid | Dermatologic (vesicles) |
| Key test | HLA-B27, SI joint imaging | ACE, lysozyme, chest CT, biopsy | Clinical; viral PCR of aqueous if atypical |
| Treatment | Topical steroids + cycloplegia | Topical/systemic steroids; IMT if chronic | Antivirals + topical steroids (with cover) |

## Sarcoid Uveitis

### Epidemiology

Sarcoidosis causes uveitis in 25-50% of affected patients. Higher prevalence in African Americans, Northern Europeans, Japanese. Anterior uveitis is the most common ocular manifestation. Bimodal age distribution: 25-35 years and 45-65 years.

### Clinical Features

**Granulomatous anterior uveitis** -- hallmark presentation. **Mutton-fat keratic precipitates** -- large, greasy, on inferior corneal endothelium. **Iris nodules** -- Koeppe (pupillary margin) and Busacca (iris stroma) **Tent-shaped peripheral anterior synechiae (PAS)**. **Chronic course** with insidious onset. **Vitreous snowballs** (string-of-pearls pattern)

Posterior segment: periphlebitis ("candle-wax drippings"), choroidal granulomas, optic disc granuloma, CME.

### Diagnostic Criteria (International Workshop on Ocular Sarcoidosis -- IWOS)

Seven intraocular signs suggestive of sarcoidosis. Laboratory and imaging: elevated ACE, elevated lysozyme, bilateral hilar lymphadenopathy on chest imaging, abnormal liver enzymes, positive gallium scan or PET. **Definite**: biopsy-proven non-caseating granulomas + compatible uveitis. **Presumed**: no biopsy but bilateral hilar lymphadenopathy + compatible uveitis. **Probable**: no biopsy, no hilar adenopathy, but 3+ supportive lab/imaging findings.

### Treatment

Topical, periocular, or systemic corticosteroids depending on severity. **Steroid-sparing immunosuppression**: methotrexate (first-line), mycophenolate, azathioprine. **Adalimumab** -- for refractory cases; FDA-approved for non-infectious intermediate, posterior, and panuveitis. Pulmonology co-management for systemic disease.

## Herpetic Anterior Uveitis

### Etiology

**HSV-1** and **HSV-2** -- most common viral cause of anterior uveitis. **VZV** (herpes zoster ophthalmicus) -- reactivation of latent virus in trigeminal ganglion. **CMV anterior uveitis** -- increasingly recognized, especially in immunocompetent Asian populations.

### Clinical Features -- HSV/VZV

**Unilateral**, acute or chronic/recurrent. **Elevated IOP** -- due to trabeculitis; key distinguishing feature. **Sector iris atrophy** -- ischemic, from vasculitis of iris vessels. **Fine to medium KP** -- may be stellate or diffuse; can be granulomatous. **Reduced corneal sensation** -- neurotrophic keratopathy. **Concurrent or prior keratitis** (dendritic or stromal)

VZV: dermatomal vesicular rash (V1 distribution); Hutchinson sign (nasal tip involvement)

### Clinical Features -- CMV

**Posner-Schlossman syndrome** (glaucomatocyclitic crisis) -- recurrent mild anterior uveitis with markedly elevated IOP (40-60 mmHg), few cells, coin-shaped KP. **Fuchs-like presentation** -- diffuse small KP, iris atrophy. Diagnosed by anterior chamber tap with PCR for CMV DNA.

### Workup

Clinical diagnosis in most cases. **Anterior chamber paracentesis with PCR** -- when diagnosis uncertain; HSV, VZV, CMV. **Goldmann-Witmer coefficient** -- ratio of intraocular to serum antibody production.

### Treatment

**HSV/VZV**: oral antivirals (valacyclovir 500-1000 mg TID or acyclovir 400-800 mg 5x/day) + topical corticosteroids + IOP-lowering agents. **Long-term antiviral prophylaxis** -- valacyclovir 500 mg daily to reduce recurrences. **CMV**: oral valganciclovir (900 mg BID induction, then 450 mg BID maintenance) or topical ganciclovir 0.15% gel. IOP management: aqueous suppressants preferred; avoid prostaglandin analogs (may exacerbate inflammation)

![Slit-lamp photograph showing mutton-fat keratic precipitates and Busacca nodule in sarcoid anterior uveitis](/images/ophthalmology/sarcoid-mutton-fat-kp-busacca.jpg)

![Photograph of herpes zoster ophthalmicus with V1 dermatomal vesicular rash and periorbital edema](/images/ophthalmology/hzo-dermatomal-rash.jpg)

## Key Clinical Pearls

HLA-B27 uveitis is characteristically acute, unilateral, recurrent, and fibrinous; always ask about back pain. Granulomatous KP with iris nodules should prompt evaluation for sarcoidosis, TB, and syphilis. Elevated IOP with anterior uveitis is the hallmark of herpetic uveitis (trabeculitis) Sector iris atrophy points strongly toward HSV or VZV etiology. CMV anterior uveitis is underdiagnosed; consider in recurrent hypertensive uveitis with coin-shaped KP.

## References

1. Rosenbaum JT. Characterization of uveitis associated with spondyloarthritis. J Rheumatol. 1989;16(6):792-796.
2. Herbort CP, et al. International criteria for the diagnosis of ocular sarcoidosis (IWOS). Ocul Immunol Inflamm. 2009;17(3):160-169.
3. Chee SP, Jap A. Cytomegalovirus anterior uveitis: outcome of treatment. Br J Ophthalmol. 2010;94(12):1648-1652.
4. American Academy of Ophthalmology. Intraocular Inflammation and Uveitis. BCSC Section 9. 2023-2024.