Uveitis in the Spondyloarthropathies Alireza Peyman, MD

Systemic association with Uveitis Spondyloarthropathies Sarcoidosis JRA IBD Behcet MS Infections HSV, Syphilis, Toxo, TB, Lyme Medications Rifabutin

What are sero-negative Spondyloarthropathies?

What does the term “seronegative” mean? a) Patients do not form antibodies b) Patients are negative for HLA-B27 c) Patients are negative for RF d) Patients are negative for ANA

Spondyloarthropathies Seronegative Spondyloarthropathy: a misnomer !! thought to be variant of RA, hence “seronegative” The spondyloarthropathies comprise a group of inflammatory arthropathies that that share a number of distinctive clinical, radiographic and genetic features. Included among this group are: Ankylosing spondylitis Reiter's syndrome (reactive arthritis) Psoriatic arthritis Enteropathic arthritis “Seronegative” spondyloarthropathies - a misnomer (implies negative tests for ANA and rheumatoid factor) Many patients will not fully manifest or meet criteria for one of the well characterized disorders above. Moreover, some patients will demonstrate overlapping features of 2 or more of these diagnoses. Hence the need for the term spondyloarthropathy. “Lumping” these disorders together allows one to seen their common genetic influences, clincal and pathologic features and predictable responses to therapies. The spondyloarthropathies share a propensity for: Inflammatory axial arthritis (sacroiliitis and spondylitis) Peripheral arthritis (often asymmetric and oligoarticular) Enthesitis: inflammation at tendinous/ligamentous insertions HLA-B27: a class I major histocompatibility complex (MHC) antigen

Definition: A group of inflammatory arthropathies that share distinctive clinical, radiographic and genetic features. These diagnoses include: Ankylosing spondylitis Reactive arthritis (Reiter's syndrome) Psoriatic arthritis Enteropathic arthritis (Crohns, Ulcerative colitis)

Family of Spondyloarthropathies IBD Associated Arthritis Reactive Arthritis Juvenile Spondylitis AS Psoriatic Arthritis Undifferentiated Spondylo- arthropathy SAPHO Acute Ant. Uveitis

Spondyloarthopathies (Criteria) Key Features: Inflammatory axial arthritis (sacroiliitis and spondylitis) Peripheral arthritis (often asymmetric and oligoarticular) Enthesitis HLA-B27 positivity XRay evidence of erosions + hyperostosis (reactive bone) Extra-axial, Extra-articular Features

Associated Extraarticular Features Periarticular: Enthesitis, tendinitis, dactylitis (sausage-digit) Ocular: Uveitis, Conjunctivitis Gastrointestinal: Painless oral ulcerations, asymptomatic gut inflammation, symptomatic colitis Genitourinary: urethritis, vaginitis, balanitis Cardiac: Aortitis, valvular insufficiency, heart block Cutaneous: keratoderma blennorrhagicum, psoriasis or nail lesions (onycholysis, dystrophy, pitting). These disorders can manifest extra-articular features that suggest a particular spondyloarthropathy. Extra-articular manifestations may involve periarticular structures (enthesitis), eyes (uveitis), gastrointestinal tract (oral ulcerations, asymptomatic gut inflammation), genitourinary tract (urethritis), heart (aortitis, heart block), skin (keratoderma blennorrhagicum) or nails (onycholysis). Occasionally patients with overlapping features of more than one condition or with HLA-B27(+) unclassifiable disease may be encountered. Thus, approaching these conditions as a group of related disorders is important in understanding their pathologic consequences and in diagnosing them accurately.

HLA-B27 Class I MHC, important in antigen presentation CD8 T cells Associated with the spondyloarthropathies HLA-B27 is a normal gene found in 8% of Caucasians 3-4% of African-Americans, 1% of Orientals. Risk developing AS in ANY HLA-B27(+) person is only 1-2%. Over 95% of patients with ankylosing spondylitis are B27+ there is 20-30% risk to 1st degree relatives of AS patients B27 increases risk of SPONDYLITIS and UVEITIS

Ankylosing Spondylitis

Ocular manifestations in ANKYLOSING SPONDYLITIS

ANKYLOSING SPONDYLITIS Non-granulomatous, recurrent, acute, anterior uveitis. Generally, one eye is affected at a time, although both eyes may suffer attacks. Occasionally anterior chamber inflammation may be severe enough to produce hypopyon, fibrin deposition, and posterior synechiae.

An estimated 25% to 40% of patients with AS suffer an attack of uveitis at some time during the course of their disease. Studies of patients with acute anterior uveitis have reported that AS is present as the underlying systemic disease in 18% to 34% of these patients.

Reactive arthritis (REITER'S SYNDROME)

Reactive arthritis have been associated with all the following except: a) Chlamydia b) Ureaplasma c) Campylobacter d) Gonorrhea

REACTIVE ARTHRITIS Acute inflammatory arthritis occuring 1-3 weeks after infectious event (GU, GI, idiopathic) TRIAD: arthritis + urethritis (vaginitis) + conjunctivitis (classic triad found in < one-third of pts) Usually asymmetric oligoarticular + extraarticular Sxs Arthritis recurrent in 15-30%, more in chlamydial arthritis pts.

HLA-B27+ in 75-80% Post-venereal onset: more common Sex 5:1 M:F Post-dysenteric: less common, equal M=F Course: self limiting (< 6 mos), chronic, intermittent Complications: Acute anterior uveitis 5%, carditis, fasciitis

Infectious Triggers for Reactive Arthritis COMMON PATHOGENS Enteric Infections Shigella flexneri, serotype 2a, 1b Salmonella typhimurium, S. enteritidis Yersinia enterocololitica Campylobacter jejuni Urogenital Infections Chlamydia trachomatis, C. pneumoniae Ureaplasma Urealyticum

KB: keratoderma blenorrhagicum

Reactive Arthritis: Treatment Antibotic TX (doxycycline, ciprofloxacin) x3 mos indicated Abx do not affect outcome of Shigella, Salmonella infection

EYE in REITER'S SYNDROME Conjunctivitis was one of the original triad described by Reiter and is one of the hallmarks of the disease. Conjunctivitis tends to be a feature of early disease, particularly of the initial attack, and may be missed if patients are seen only during subsequent attacks. The more serious ocular manifestation is recurrent, acute, nongranulomatous anterior uveitis.

Anterior uveitis occurs in approximately 5% to 20% of patients with the initial attack but may occur in as many as 50% of patients with Reiter's syndrome over long-term follow-up.

Rarely other forms of posterior ocular involvement such as multifocal choroiditis have been reported in Reiter's syndrome. Rarely, patients may develop a keratitis with punctate epithelial lesions, progressing to a central loss of the corneal epithelium and subepithelial infiltrates.

What is the diagnosis? Bad manicure Rheumatoid arthritis Psoriatic arthritis Erosive OA

PSORIATIC ARTHRITIS Chronic inflammatory arthropathy in setting of psoriasis Etiology and genotype unclear Nail changes: pitting, dystrophy, onycholysis Course: chronic, destructive arthritis in 30-50%

Classification of Psoriatic Arthritis Type Key Clinical Features Incidence Asymmetric polyarthritis or oligoarthritis Morning stiffness, DIP and PIP involvement, nail disease,  4 joints involved 40% Symmetric polyarthritis Symmetric polyarthritis, RA-like distribution, but RF negative 25% Spondylitis Inflammatory low back pain, sacroilitis, axial involvement, 50% HLA-B27+ 20% Distal interphalangeal joint disease Nail changes, often bilateral joint involvement 15% Arthritis mutilans Destructive form of arthritis, telescoping digits, joint lysis, typically in phalanges and metacarpals <5%

Pencil and Cup Deformity

EYE in PSORIATIC ARTHRITIS

PSORIATIC ARTHRITIS Conjunctivitis occurs in approximately 20% to 33% of patients with psoriatic arthritis, iritis in 4% to 7% scleral disease in 2%.

Patients with psoriatic spondylitis typically develop a nongranulomatous, recurrent, acute anterior uveitis, as is the case with other HLA-B27–associated arthropathies, but chronic uveitis also may occur. Brown's syndrome also has been reported in patients with psoriatic arthropathy.

ARTHRITIS WITH INFLAMMATORY BOWEL DISEASE

ENTEROPATHIC ARTHRITIS 5-20% of IBD patients (Crohns disease or Ulcerative colitis) will develop inflammatory arthritis Risk increases with extent of colonic dz and presence of other extraintestinal manifestations: abscesses, E. Nodosum, uveitis, pyoderma gangrenosum Gut disease may be asymptomatic for years

Subsets: Asymmetric oligoarthritis (intermittent or chronic) Seronegative RA-like polyarthritis 20% of IBD pts Spondylitis 10-15% (may be misdiagnosed as AS) Peripheral arthritis parallels the gut! NOT THE SPINE!

IBD associated eye disease Ocular inflammation typically occurs in approximately 2% to 6% of patients. The ocular manifestations include anterior uveitis, scleritis, and keratitis.

Anterior uveitis is the most common ocular manifestation. More often it presents as a nongranulomatous, recurrent, acute anterior uveitis. Chronic and bilateral uveitis also occurs occasionally and may be seen more frequently in women with IBD.

All types of scleritis have been associated with IBD including anterior scleritis, necrotizing scleritis, and posterior scleritis. The scleral inflammation may parallel the activity of the underlying bowel disease Rarely, keratitis and Brown's syndrome may be seen in association with IBD.

Thank you for your attention!