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A. Types of Disordersnavigator

  1. Ankylosing Spondylitis
  2. Psoriatic Arthritis
  3. Enteropathic (IBD Associated) Arthritis (see below)
  4. Reactive Arthritis and Reiter's Syndrome
  5. Undifferentiated Spondyloarthropathy
  6. Common Findings
    1. Inflammatory back pain - sacroiliitis ± additional axial inflammation
    2. Asymmetric peripheral oligoarthritis
    3. Enthesitis
    4. Specific organ involvement (uveitis, others)
    5. Genetic linkage through major histocompatility complex (MHC) class I molecule HLA-B27

B. Disease Relationshipsnavigator

  1. Majority of patients are male
  2. Strong Family History
  3. HLA-B27 association with all of the spondyloarthropathies
    1. Ankylosing Spondylitis ~90%
    2. Reactive Arthritis ~60%
    3. Juvenile Spondyloarthropathy ~70%
    4. Enteropathic Spondyloarthropathy ~55%
    5. Psoriatic Arthritis ~45%
    6. Undifferentiated Spondyloarthropathy ~70%
    7. Acute anterior uveitis (acute iritis) ~50%
    8. Aortic incompetence with heart block ~80%
  4. ANA (antinuclear antibody) and RF (rheumatoid factor) usually negative
  5. The arthritis in all of these syndromes is usually asymmetrical

C. Undifferentiated Spondyloarthropathynavigator

  1. Variety of isolated clinical syndromes
  2. Most commonly HLA-B27 associated seronegative oligo- or polyarthritis
  3. Mainly affects lower extremities
  4. No clear infectious precipitation or underling inflammatory disorder
  5. Common Symptoms
    1. Dactylitis: "sausage digits"
    2. Enthesitis - especially of heel (Achilles tendonitis, plantar fasciitis)
  6. Other Associations with HLA-B27
    1. Acute anterior uveitis (iritis)
    2. Aortic incompetence with heart block
  7. Spondyloarthropathy may occur prior to, during, or after onset of other symptoms
  8. Sulfasalazine did not have activity in this condition [3]

ANKYLOSING SPONDYLITIS [2]

A. Characteristicsnavigator
  1. ~70% of patients are male
  2. HLA-B27 Association
    1. Overall, ~90% of patients are HLA-B27 positive
    2. ~8% of caucasians are also HLA-B27 positive (without disease)
    3. Overall ~87X risk of disease in Caucasians with HLA-B27
    4. There are serologically related MHC proteins with similar peptide binding regions
    5. If these are included in the frequency of MCH-related disease, it approaches 100%
  3. Onset usually in childhood or early adulthood
    1. May present as pauciarticular JRA in boys
    2. Generally present around age 26 years
  4. Significant incidence of asymptomatic GI inflammation
    1. Ileal inflammation in ~20% of patients with spondyloarthropathy (no GI symptoms)
    2. No association of gut lesions with HLA-B27 or use of NSAIDs
    3. Crohn's Disease - found in ~19% patients with chronic spondyloarthropathy
  5. Cardiac Manifestations
    1. Aortic Insufficiency - most common
    2. Conduction disturbances - mainly atrioventricular node leading to heart block
    3. Myocarditis - may lead to left ventricular dysfunction

B. Role of HLA-B27navigator

  1. HLA-B27 Serologic Family
    1. Comprises a family of 25 proteins (subtypes of HLA-B27)
    2. These are designated HLA-B*2701 through HLA-B*2725
    3. HLA-B*2705 is most common subtype
  2. Strong correlation with caucasian patients with HLA-B27 and development of AS
    1. However, ~8% of caucasians express HLA-B27
    2. Only ~10% of these persons will develop AS or related disorder
    3. Majority of subtypes of HLA-B27 linked with increased AS risk
  3. HLA-B*2706 in southeast asia and -B*2709 in Sardinia appear not associated with AS
  4. Expression of HLA-B27 in transgenic rats leads to AS-like illness
  5. Linkage in families with AS shows strong correlation between AS and HLA-B27
    1. Risk of spondyloarthropathy in relative of HLA-B27+ AS patient is ~30%
    2. This is 3X expected rate which is ~10%

C. Symptomsnavigator

  1. Inflammatory back pain due to sacroilitis, inflammation of other axial skeletal areas
  2. Pain and stiffness more common in AM and after rest
  3. Pain and stiffness somewhat relieved by activity
  4. Peripheral oligoarthritis, assymetric
  5. Enthesitis - pain, tenderness on tendon insertions
  6. Anterior uveitis
  7. Juvenile Disease
    1. Often presents as tenosynovitis
    2. Uveitis is not uncommon but is often asymptomatic
    3. Most common in boys <8 years old
    4. May be classified as pauciarticular juvenile chronic arthritis (JCA)

D. Physical Examinationnavigator

  1. 4-Point (Occiput to Wall) Test
    1. Patient stands against wall
    2. Normally, occiput, shoulders, iliac crests and feet can touch wall
    3. One or more of these do not touch in AS
  2. Wright-Schober Test
    1. Mark LS junction in standing position
    2. Measure 10cm above that
    3. Have patient flex at the waist
    4. Normal increase in measurement is 5cm (total 15cm) between above patients
  3. Chest Expansion
    1. Normal is 2-3cm, though most can expand >6cm
    2. Expansion <2cm is moderate to severe AS
  4. SI Joint Exam
    1. Flex one knee
    2. Extend other leg - pain in SI joint consistent with sacroiliitis
  5. Cardiac Disease [4]
    1. Appears to correlate with presence of HLA-B27
    2. Aortic regurgitation due to aortic dilation
    3. Increased incidence of heart block and obliterative endarteritis
    4. Aggressive therapy, valve replacement, pacemakers, may be required
  6. Careful eye examination for evidence of uveitis (typically anterior)

E. Radiographic Changes [5] navigator

  1. Plain radiographs were previously standard of diagnosis
    1. Squaring of vertebrae in LS Region
    2. Sacroiliitis
    3. Syndesmophytes - intervertebral bony "bridging" (ossification of annulus fibrosus)
    4. Later stage - complete ossification of spinal ligaments leading to fused ("bamboo") spine
  2. Early changes are best viewed with magnetic resonance imaging of sacroiliac joints
  3. Sacroilliitis
    1. Sclerosis of periarticular (SI) bone
    2. Obliteration of joint space
  4. May have peripheral changes, nonerossive polyarthritis
  5. Bone mineral density (BMD) is often reduced

F. Treatment See Card "Rheumatologic Therapeutics"navigator

  1. NSAIDs See Card "Prostaglandin Pharmacology"
    1. Indomethacin good efficacy
    2. High dose ibuprofen also moderately effective
  2. Blockade of Tumor Necrosis Factor alpha (TNFa) [6]
    1. TNFa plays a key role in joint destruction
    2. Infliximab improves symptoms, reduces progression, and induces disease regression in >50% of patients with active AS [7]
    3. Etanercept 25mg sc twice weekly induces responses in 80% of patients including reduction of pain and stiffness, and improved functioning both axial and peripheral [8]
    4. TNFa blocade is most effective treatment to date; also has disease modifying activity
    5. TNFa blockade should be offered to any patient with significant symptoms after NSAIDs ± sulfasalazine [3]
  3. Sulfasalazine (Azulfidine®) [3]
    1. Begin 500mg po bid x 1 week; then dose is increased to 1000mg po tid
    2. Olsalazine may also be used; dose initiation is the same with increase to 3gm / day
    3. Modest benefit over placebo, mainly on easing spinal stiffness, reducing ESR [10,11]
    4. Sulfasalazine does not appear to alter progression of disease
    5. Well tolerated; major side effects are diarrhea and nausea (~20% overall)
    6. G6PD deficient patients should not receive sulfasalazine due to high risk of hemolysis
  4. Methotrexate (MTX) [3]
    1. Doses of 20mg q week (SC or IM) oir higher likely required for any activity in AS
    2. Some modest reduction in peripheral but not axial disease symptoms
    3. Unclear if MTX changes progression of disease
    4. TNFa blockers are generally preferred
  5. Physical therapy is a critical component
  6. Pacemaker may be required in patients with severe cardiac conduction disease [4]

IBD ASSOCIATED (ENTEROPATHIC) ARTHRITIS [1]

A. Characteristics navigator
  1. ~20% of IBD (Crohn Disease and Ulcerative Colitis)
  2. May affect primarily Peripheral joints and Axial (Spondylitis) joints, or both

B. Axial formnavigator

  1. Associated with HLA-B27 in ~55% of cases
  2. Chronic and progressive
  3. Does not respond well to IBD therapy

C. Peripheral Formnavigator

  1. Ankles, Knees, Elbows
  2. Pauci-articular arthritis, related to activity of IBD and responds to therapy

D. IBD Arthropathy Associationsnavigator

  1. Erythema nodosum
  2. Pyoderma Gangrenosum
  3. Mucosal Ulcers

E. Treatmentnavigator

  1. Axial disease does not respond well to therapy
  2. Sulfasalazine has good activity in IBD-associated arthritis, particularly peripheral form
  3. Methotrexate may be the agent of choice in chronic joint disease
  4. Axial and peripheral arthropathy also improved after anti-TNFa antibody (infliximab) in 4 patients with severe Crohn's Disease [9]

References navigator

  1. Khan MA. 2002. Ann Intern Med. 136(12):896 abstract
  2. Braun J and Sieper J. 2007. Lancet. 369(9570):1379 abstract
  3. Braun J, Zochling J, Baraliakos X, et al. 2006. Ann Rheum Dis. 65(9):1147 abstract
  4. Bergfeldt L. 1997. Ann Intern Med. 127(8):621 abstract
  5. Lee YS, Schlotzhauer T, Ott SM, et al. 1997. Am J Med. 103(3):233 abstract
  6. Davidson A and Diamond B. 2001. NEJM. 345(5):340 abstract
  7. Braun J, Brandt J, Listing J, et al. 2002. Lancet. 359(9313):1187 abstract
  8. Gorman JD, Sack KE, Davis JC Jr. 2002. NEJM. 346(18):1349 abstract
  9. Van den Bosch F, Kruithof E, De Vos M, et al. 2000. Lancet. 356(9244):1821 abstract
  10. Chen J and Liu C. 2006. J Rheumatol. 33(4):722 abstract
  11. Clegg DO, Reda DJ, Weisman MH, et al. 1996. Arthritis Rheum. 39(12):2004 abstract
  12. Clegg DO, Reda DJ, Weisman MH, et al. 1996. Arthritis Rheum. 39(12):2021 abstract