Eliza Hoskins

BASICS

DESCRIPTION

• Non-granulomatous anterior uveitis (NGAU) is a broad classification for various inflammatory conditions localized to the iris (iritis), ciliary body (cyclitis), or both (iridocyclitis) that typically present with pain, redness, and photophobia.

– Etiologies can be infectious or immune-mediated

– Systemic involvement or isolated to the eye

– NGAU is characterized by small punctate or stellate keratic precipitates (KP) versus granulomatous anterior uveitis with large greasy mutton fat KP with iris nodules or choroidal granulomas.

EPIDEMIOLOGY

Incidence

• 8–17 cases per 100,000 population (1,2)

• HLA-B27 more common in Caucasian males

• Behçet’s disease is more common in Asian and Middle- Eastern males

• Juvenile idiopathic arthritis (JIA) more common in females.

RISK FACTORS

• Trauma

• Genetic predisposition (HLA-B27, HLA-B51)

• Smoking (3)

Genetics

• HLA-B27 (ankylosing spondylitis (AS)), reactive arthritis (formerly Reiter’s syndrome), inflammatory bowel disease (IBD), psoriatic arthropathy

• HLA-B51 (Behçet’s disease)

GENERAL PREVENTION

No prevention of idiopathic NGAU.

ETIOLOGY

• Idiopathic (50%)

• 30% AS patients have NGAU

COMMONLY ASSOCIATED CONDITIONS

See Review of Systems (ROS).

DIAGNOSIS

HISTORY

Targeted history onset, duration, location, quality of symptoms, and associated conditions. Clinical course (acute, chronic, or recurrent) laterality and previous treatments/trauma.

• Standardization of uveitis nomenclature (SUN) (4)

– Acute: Sudden onset with limited duration.

– Recurrent: Repeat episodes separated by periods of inactivity without treatment >3 months in duration

– Chronic: Persistent uveitis with relapse <3 months after discontinuing treatment

• Past medical, social, and family history

– Infectious disease exposure

– Autoimmune/Rheumatologic disease

– STDs/IVDU

– Medications: Rifabutin, Cidofovir, Prostaglandins

– Pets: Cats-Toxoplasmosis, puppies-Toxocariasis

– Family history: HLA-B27

• Review of systems (ROS):

– Constitutional: Fever, night sweats, chills (Infectious-endogenous endophthalmitis, tuberculosis), weight loss (malignancy)

– Skin/mucocutaneous: Erythema nodosum (IBD, Behçet’s, sarcoid) erythema chronicum migrans (Lyme), polyarteritis nodosa (PAN), aphthous/oral ulcers (Behçet’s, herpetic), scaling lesions (psoriasis, reactive arthritis), vitiligo, (Vogt Koyanagi Harada (VKH))

– Musculoskeletal: Sacroiliitis (ankylosing spondylitis, reactive arthritis, IBD); Monoarticular/pauciarticular arthritis (JIA), fasciitis/tendonitis (reactive arthritis)

– Respiratory: Asthma, wheezing, shortness of breath, cough (sarcoid, TB, coccidioidomycosis), sinus, and pulmonary disease (Wegener’s granulomatosis)

– Cardiovascular: Pericarditis (reactive arthritis, Lyme), thrombophlebitis (Behçet’s), AV block (Lyme)

– Gastrointestinal: Diarrhea (IBD, reactive arthritis)

– Genitourinary: Urethritis/circinate balanitis (reactive arthritis, syphilis), epididymitis (reactive arthritis, Behçet’s), genital sores/ulcers (syphilis, reactive arthritis, HSV, Behçet), urinary incontinence (Multiple sclerosis (MS)), elevated creatinine, abnormal urinalysis (Tubulointerstitial nephritis and uveitis syndrome (TINU))

– Hematological: anemia/elevated ESR (TINU)

– Neurologic: Meningitis (Behçet’s, Lyme, sarcoid, VKH), cranial nerve palsies (sarcoid, lyme, lymphoma, MS)

PHYSICAL EXAM

• External: Skin, joints, oral cavity, lymph nodes, neurologic, genitourinary

• Pupils: Irregular/secluded pupil (posterior synechiae), miotic and/or accommodate but don’t react to light (syphilis-Argyll Robertson pupil)

• Intraocular pressure:

– Acute increased IOP: Herpetic (trabeculitis), Fuchs’ heterochromic iridocyclitis, Glaucomatocyclitic crisis

• Gonioscopy: Peripheral anterior synechiae (PAS), KP, abnormal angle vessels-”Amsler sign” (Fuchs’)

• Eyelids/lashes: Vesicles (HSV), vitiligo (VKH), poliosis (white eyelashes) (VKH)

• Conjunctiva/Sclera: Circumferential ciliary flush, granulomas (sarcoid, TB), papillo-follicular conjunctivitis (reactive arthritis or Reiter’s Syndrome) conjunctival dendrites (herpetic), episcleritis/scleritis (IBD, RA, SLE, Wegener’s)

• Cornea: Decreased corneal sensation (herpetic), diffuse-stellate KP (Fuchs’, herpetic), band keratopathy (JIA, chronic uveitis), stromal edema (herpetic), peripheral ulcerative keratitis (Rheumatoid arthritis (RA), IBD, systemic lupus erythematosus (SLE), Wegener’s, PAN)

• Iris/anterior chamber/angle: Posterior synechiae, pupillary membranes, iris nodules (sarcoid- Koeppe-pupillary margin, Busacca-throughout iris), transilluminatory defects (TID’s)/atrophic iris (herpetic, UGH), heterochromia (Fuchs’), hypopyon (HLA-B27, Behçet’s, Retinoblastoma (Rb), infectious), hyphema (Herpetic, Fuchs’, juvenile xanthogranuloma (JXG), Rb, neovascularization of the iris/angle, leukemia)

• Anterior chamber reaction: Grading cell/flare: SUN (1 x1 mm² slit beam) (4)

– Grade 0 (<1 cells)/complete absence

– Grade 0.5+ (1 – 5 cells)/n/a

– Grade 1+ (6–15 cells)/Faint

– Grade 2+ (16–25 cells)/Moderate (iris & lens clear)

– Grade 3+ (26–50 cells)/Marked (iris & lens hazy)

– Grade 4+ (>50 cells)/Intense (fibrin, plastic aqueous

• Lens/anterior vitreous: Lenticular precipitates, posterior subcapsular cataracts (chronic inflammation and topical/oral steroids), haptic induced TID’s (UGH), retained lens fragment, cyclitic membrane

• Dilated fundus examination: Vitreitis, snowballs, snowbanking (MS), cystoid macular edema (CME), vasculitis (Behçet’s), Toxoplasmosis scars, retinal necrosis/whitening (herpetic, acute retinal necrosis (ARN)), choroidal infiltrates (sarcoid, Birdshot, VKH, Dalen-Fuchs’ nodules), intraocular foreign body

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

Workup indicated if bilateral, severe, recurrent/nonresponsive to treatment or guided by History/ROS:

• RPR, FTA-ABS, CXR, ACE, HLA-B27, PPD (or quantiferon if vaccinated), Lyme Ab

– Target labs according to ROS and anatomic location of inflammation (anterior, intermediate, posterior, panuveitis)

– Consider ANA, rheumatoid factor if JIA is suspected: Girls: ANA +, RF- and pauciarticular; Boys: HLA-B27+, ANA-, RF-

– Consider ANCAs, ESR, CRP if associated scleritis and/or peripheral ulcerative keratitis Wegener’s/polyarteritis nodosa (PAN), rash (PAN), pulmonary/sinus disease (Wegener’s)

– Consider urinalysis for β₂ microglobulin level, renal biopsy if suspect TINU

Follow-Up & Special Considerations

• Glaucoma

– Angle closure glaucoma (PAS)

– Pupillary Block glaucoma (Secluded pupil)

– Elevated IOP: Steroid induced glaucoma

• Posterior subcapsular cataract

• Cystoid macular edema (CME)

Imaging

• CXR (Sarcoid, TB)

– Consider CT-chest, pulmonary function tests

• X-ray-sacroiliac joints (HLA-B27, ankylosing spondylitis)

• B scan if there is no view to posterior pole

• Fluorescein angiogram (CME, vasculitis, retinal/choroidal infiltrates)

• OCT for CME monitoring

Diagnostic Procedures/Other

• Anterior chamber/vitreous tap: PCR: herpetic or toxoplasmosis-correlate with serology, Cytology: lymphoma or leukemia

• Conjunctival biopsy (caseating vs. non-caseating granulomas)

Pathological Findings

• Small/medium KP: Neutrophils and lymphocytes

• Large (mutton fat) KP: Macrophages granulomatous

– Note: Granulomatous disease can present with small/medium KP.

DIFFERENTIAL DIAGNOSIS

• HLA-B27

– Ankylosing spondylitis

– Psoriatic arthropathy

– Inflammatory bowel disease (IBD)

– Postinfectious, or reactive arthritis (formerly Reiter’s syndrome)

• Juvenile idiopathic (rheumatoid) arthritis (JIA)

• Herpetic disease

– Herpes Simplex virus

– Varicella Zoster virus

– Cytomegalovirus

• Glaucomatocyclitic crisis (Posner-Schlossman syndrome)

• Fuchs’ heterochromic iridocyclitis

• Behçet’s disease

• Tubulointerstitial nephritis and uveitis syndrome (TINU)

• Traumatic iritis

• Lens-associated uveitis

– Phacolytic

• IOL-associated uveitis: Uveitis, glaucoma, hyphema (UGH)

• Drug induced uveitis

• Lymphoma

• Idiopathic uveitis

NOTE: Syphilis, sarcoidosis, tuberculosis (TB), VKH, and Lyme disease are in the differential diagnosis, but are classified as granulomatous.

TREATMENT

MEDICATION

First Line

• Topical steroids

– Prednisolone acetate 1% q 1–2 hour during first week and slowly taper over 4–6 weeks.

– Difluprednate 0.05% (Durezol) q.i.d = Prednisolone acetate 1% q2h

• Topical cycloplegics (ciliary spasm, prevention of posterior synechiae)

– Homatropine 5% b.i.d–t.i.d

• Sub-tenons steroid injection for chronic uveitis and/or CME. Consider short-acting prep such as dexamethasone phosphate if steroid response is a concern.

• Oral antiviral if herpetic disease suspected

Second Line

• Oral prednisone (1 mg/kg/d) (max 60–80 mg) do not continue at high dose >1 month. If there is no response after 2–4 weeks or fails a slow taper, steroid sparing immunosuppressive should be considered.

• Calcium 1500 mg and Vitamin D 800 IU (bone density prophylaxis)

• H₂ Blockers (GI prophylaxis)

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