Spondyloarthropathies

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

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.

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%

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

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 50-80% • 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%

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

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

14. Ankylosing Spondylitis - Epidemiology • Strong HLA-B27 association in all populations • In Caucasians, AS occurs with a prevalence of 0.5-1.0% • 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

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.

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

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

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.

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

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.

29. Reactive Arthritis: Triggering Infections • Urogenital Tract • Chlamydia trachomatis • Ureaplasma urealyticum • Gastrointestinal Tract • Yersinia enterocolitica • Yersinia pseudotuberculosis • Salmonella • Shigella • Campylobacter • Respiratory Tract • Chlamydia pneumoniae

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.

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.

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 notmake 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