1. Spondyloarthropathies
Brian E. Daikh, MD
7/21/09

2. Case:
Hx:
20 y.o. male with months of left knee swelling.
occasional mouth sores
1 episode of bloody diarrhea with ibuprofen
4 years of back stiffness
A brother has psoriasis
Exam:
Left knee warm with a moderate effusion
Spinal flexion limited
Question: What is the DDx and what further information is needed to determine a diagnosis in this patient?

3. Spondyloarthropathy: Definitions
A group of inflammatory arthridites Characterized by:
Synovitis
Enthesitis – inflam. Where tendon connects to bone
Spinal and Peripheral Joint Involvement
Genetic Predisposition
Probable Infectious Cause
Categories
Ankylosing Spondylitis
Reactive Arthritis
Psoriatic Arthritis
Enteropathic Arthritis – Crohn’s disease, Ulcerative Colitis
Undifferentiated
Don’t see these characteristics in Rheumatoid arth.

4. Spondyloarthropathy: Clinical and Laboratory Features
Sacroileitis or spondylitis (inflam of ligaments that connect to vert bodies)
Peripheral arthritis:
Typically asymmetric and involves the lower limb;
Upper limb involvement often associated with Psoriatic Arthritis
Enthesopathy -inflammation at the site of tendinous or ligamentous insertion
Extra-articular manifestations occur in the minority
By definition, patients are RF factor negative
HLA-B27 is present in many individuals, depending on the type of arthritis.
RF (rheumatoid factor)

5. ACR Diagnostic Criteria for Spondyloarthropathy
Inflammatory Spinal Pain or Joint Synovitis (Asymmetric or predominantly lower limbs)
AND 1 of the following:
Positive family history
Psoriasis
IBD
Urethritis or Cervicitis (nongonococcal), or acute diarrhea within 1 month
Buttock pain
Enthesopathy
Sacroileitis
Sensitivity 78.4% and specificity 89.6%
Morning stiffness in pelvic or back that gets better c physical activity

6. Differences between RA and Spondyloarthropathy
RA Spondy
Peripheral Arthritis polyarticular pauciarticular
Sacroileitis x
Spondylitis x
Enthesitis x
Subcutaneous Nudules x
Rheumatoid Factor x
Symmetry x
Pauciarticular - < 5 joints

7. Spondylarthropathies: nonvertebral manifestations
Asymmetric peripheral arthritis
Sausage digits
Enthesopathy
Achilles tenosynovitis
Plantar fasciitis
Costochondritis
Acute anterior uveitis/iridocyclitis
Mucocutaneous lesions
Nail involvement
Fatigue, weight loss
Amyloidosis
Apical pulmonary fibrosis
Immunoglobulin A nephropathy
Cardiac involvement

8. HLA-B27 disease associations
Ankylosing spondylitis > 90% (white males)
with uveitis or aortitis ~100%
Reactive arthritis %
with sacroiliitis or uveitis 90%
Juvenile spondylarthropathy 80%
Inflammatory bowel disease
Peripheral Not increased
Axial
Crohn’s disease 50%
Ulcerative colitis 70%
Psoriasis
Peripheral Not increased
Axial 50%
Having gene is a risk factor, but is a poor screening test.
There is a genetic risk, but doesn’t mean pt will ever get disease

9. HLA-B27
A member of the MHC Class I gene family
Important in the presentation of processed antigen to T-cells
Present in 9-11% of the caucasion population.
A poor screening test; if absent, it is unlikely the patient has ankylosing spondylitis, but if present, it does not mean the patient has disease.

10. Pathogenic Role of HLA-B27
The mechanism is not well defined.
Arthritogenic Peptide Theory: HLA-B27 may bind unique peptides of self or bacterial origin.
Molecular Mimicry Theory: Antibodies directed against foreign antigens cross-react with HLA-B27.
Aberrant Processing Theory: Abnormal folding of protein or expression of heavy chain dimers on the cell surface may lead to abnormal antigen presentation.

11. Enthesitis Swollen, erythemetous, tender
Source of inflam is where ligament/tendon attaches to bone
- recruits osteoblasts
- builds bridge across bone and “fuses” bone (ostification of ligaments)
- occurs throughout skeleton

12. Ankylosing Spondylitis

13. Ankylosing Spondylitis: Definition and Clinical Features
A chronic inflammatory arthritis that mainly affects the axial skeleton
Typical presentation is with low back pain of insidious onset
Arthritis of the hips and shoulders and enthesopathies are common
Extra-articular manifestations include: uveitis and rarely aortic valve disease and cauda equina syndrome
Spine and eye inflamm

14. Ankylosing Spondylitis - Epidemiology
Strong HLA-B27 association in all populations
In Caucasians, AS occurs with a prevalence of %
M:F 5:1
Incidence and prevalence may be underestimated due to variance in clinical presentation

15. Characteristics of Back Pain
Onset
Insidious
Often before age 40
Duration greater than 3 months
Associated with prominent morning stiffness
Improves with activity
Not pain, just stiffness

16. Ankylosing Spondylitis-Initial Management
History and physical exam
Appropriate history of morning stiffness, measurement of spinal mobility, examination of peripheral joints, eyes, mouth, skin.
Laboratory evaluation
CBC, CRP, HLA-B27?
X-rays
Lumbar spine and sacroiliac joints. C-spine if appropriate
Other possible modalities-not standard of care at this time.
MRI of the lumbar spine and SI joints if plain x-rays are normal.
May ankylos (fuse) spine if not taken care of
Syndesmophytes – fusion of cervical vertebrae/calcification of ligaments

17. AS: Management
Early diagnosis, patient education, and physical therapy are essential
Goals of PT are to restore and maintain posture and movement to as near to normal as possible
Self-management with exercise must be lifelong
NSAIDS relieve pain and stiffness, but are not disease-modifying
Sulfasalazine and Methotrexate may be effective (no controlled clinical trials)
Anti-TNFα agents are very effective in controlled trials. These are the only FDA approved therapies.

18. Psoriatic Arthritis

19. Psoriatic Arthritis - Definition
An inflammatory arthritis associated with psoriasis
May occasionally be present in the absence of clinically evident psoriasis

21. Isolated to spine without peripheral
AM – lengths change on fingers/ collapse down due to lack of skeletal integrity

22. Psoriatic Arthritis: Imaging
Common involvement of wrists, hands, feet, and shoulders.
In contrast to RA, osteopenia is not observed and DIP joint involvement is common.
Classic “pencil-in-cup” deformity
May have erosion adjacent to ankylosis or new bone formation
Periostitis
Tend to preserve bone density – (Osteopenia)
Pencil in cup = PA and nothing else! EXAM pathognomonic

23. Psoriatic arthritis-initial evaluation
History and physical exam
Close attention to the subtle findings of psoriasis, e.g. scalp involvement, nail pitting. Complete joint exam, including spinal mobility.
Laboratory evaluation
CBC, chemistries, CRP, RF, anti-CCP antibody (these are to exclude RA, really)
Baseline x-rays if appropriate
If the disease is of fairly early onset, baseline x-rays may be normal.
Look closely at skin.
Serology to exclude RA – may look really similar but these not typically seen in PA

24. Psoriatic Arthritis - Treatment
NSAIDS – mild disease, symptom relief
Intra-articular corticosteroids
DMARDS
Plaquenil – mild disease
Sulfasalazine – mild disease
MTX – moderate-severe disease
Anti-TNFα agents (These are the only drug approved by the FDA for the treatment of PsA!) – used in methotrexate nonresponders.

25. Reactive Arthritis

26. Reactive Arthritis: Definitions
Sterile joint inflammation that develops after a previous infection
The disease is systemic and not limited to the joints
Triggering infections most commonly originate in the throat, urogenital organs, or GI tract
May go to skin eye etc

27. Epidemiology of Reactive Arthritis
Most commonly affects young adults
M = F
Annual incidence 30-40/100,000
Worldwide distribution
Genetic association – HLA-B27
Frequently associated with infections

28. Reactive Arthritis: Clinical Features
Arthritis, enthesitis, tendonitis, tenosynovitis, periostitis, and muscle pain
Skin and mucous membrane lesions are frequent – oral ulcers and keratoderma blenorrhagicum
Eye inflammation (uveitis and conjunctivitis)
Visceral involvement (nephritis and carditis) is rare
Severity ranges from mild arthralgias to disabling disease
Spontaneous recovery is common and the prognosis is, in general, good
Recurrences are not uncommon
Susceptibility to the disease is strongly linked to HLA-B27 antigen positivity.
Can be all over the place

29. Reactive Arthritis: Triggering Infections
Urogenital Tract
Chlamydia trachomatis
Ureaplasma urealyticum
Gastrointestinal Tract
Yersinia enterocolitica
Yersinia pseudotuberculosis
Salmonella
Shigella
Campylobacter
Respiratory Tract
Chlamydia pneumoniae
Swollen joints present after active infection. May still find org. by doing cultures.

30. Reactive arthritis-initial evaluation
History and physical exam
Appropriate questioning for prodromal illness
Laboratory evaluation
CBC, chemistries, CRP, urethral or cervical swabs, stool culture, throat culture.
Pt will tell story. Very indicative. Make sure to ask about prodrome of illness.
May still identify org. so do cultures. Tx of infection will not tx arthritis

31. Reactive arthritis-clinical course
The clinical course is extremely variable.
The majority of patients have a relatively short, self-limited course. These patients are often treated successfully with NSAIDs, corticosteroids, and sometimes a short courses of DMARD’s.
Alternative courses include a waxing and waning course over a period of months or years more chronic, persistent inflammatory arthritis. These patients require treatment with DMARD’s.

32. Reactive Arthritis: Treatment
Antibiotics – probably not helpful
NSAIDS – symptomatic relief
Sulfasalazine – may be disease modifying, peripheral joints > axial skeleton
Methotrexate – May be disease modifying
Anti-TNFα Agents – may be very effective

33. Conclusions
The Spondyloarthropathies are a diverse group of inflammatory arthropathies that share the characteristics of arthritis and enthesitis.
HLA-B27 likely plays a pathogenic role in many of these conditions.
Extraarticular manifestations are uncommon, but may be severe.
3. Eye inflammation, skin, stomach etc.

34. Spondyloarthropathies – Clinical Pearls
All of these conditions are diagnosed primarily based on clinical features.
Extra-articular manifestations (skin, eye, GI) may provide important clues.
X-rays (sacroileitis, spondylitis, erosions) may also provide clues to the Dx.
Lab tests will not make the Dx

35. Spondyloarthropathies – Clinical Pearls
Mild disease (low grade swelling, normal acute phase labs – NSAID, Plaquenil, Sulfasalazine
Mild-Moderate disease – Sulfasalazine or Methotrexate – except spine – consider TNF blocker.
Moderate – Severe disease – begin with Methotrexate
Plaquenil and Sulfasalazine will not affect the skin in Psoriatic Arthritis