1. Uveitis in the Spondyloarthropathies
Alireza Peyman, MD

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

3. What are sero-negative Spondyloarthropathies?

4. 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

5. 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

6. 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)

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

8. 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

9. 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.

10. 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

11. Ankylosing Spondylitis

16. Ocular manifestations in ANKYLOSING SPONDYLITIS

17. 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.

18. 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.

20. Reactive arthritis (REITER'S SYNDROME)

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

22. 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.

23. 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

24. 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

25. KB: keratoderma
blenorrhagicum

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

28. 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.

29. 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.

30. 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.

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

34. 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%

35. 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%

39. Pencil and Cup Deformity

40. EYE in PSORIATIC ARTHRITIS

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

42. 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.

43. ARTHRITIS WITH INFLAMMATORY BOWEL DISEASE

44. 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

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

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

47. 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.

48. 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.

49. Thank you for your attention!