ANKYLOSING SPONDYLITIS

ANKYLOSING SPONDYLITIS - Jane S. Kim, MD
BASICS
DESCRIPTION
Ankylosing spondylitis (AS) is a chronic inflammatory seronegative arthritis affecting the axial skeleton with primary involvement of the sacroiliac joint.
• System(s) Affected: Musculoskeletal
• Synonym(s): Rheumatoid spondylitis; Marie-Strumpell disease
EPIDEMIOLOGY
• Predominant age: Onset usually in early 20s, rarely occurs after age >40 years of age
• Predominant sex: Male > Female (3:1)
Incidence
• In white males: 0.5-5 per 1,000
• Less common in women and African Americans
Prevalence
0.1-0.2% in United States
RISK FACTORS
• HLA-B27 (1% of HLA-B27-positive adults likely to have AS)
• Positive family history
- 10% risk of developing AS for HLA-B27-positive child of spondylitic parent
Genetics
Familial clustering and higher than expected frequency of HLA-B27 tissue antigen
PATHOPHYSIOLOGY
Inflammation at the insertion of tendons causes new bone formation (enthesitis).
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Uveitis (25-30%)
• Iritis
• Psoriasis
• Aortic insufficiency (2%)


DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Insidious onset
• Duration >3 months
• Morning stiffness
• Frequently awaken at night to "walk off" stiffness
• Improvement in stiffness with activity
• Increased symptoms with rest
• Hip, shoulder, or knee complaints
• Constitutional symptoms (fatigue, weight loss, low-grade fever)
Physical Exam
• Subgluteal or low back pain and/or stiffness
• Pleuritic chest pain often an early feature
• Diminished range of motion in the lumbar spine in all three planes of motion
• Loss of lumbar lordosis
• Thoracocervical kyphosis (rarely occurs before 10 years of symptoms)
• Aortic regurgitation murmur (1%)
• Acute anterior uveitis
• Osteoporosis
• Plantar fasciitis
• Peripheral arthritis (20-30%)
TESTS
• Synovial fluid: Mild leukocytosis, decreased viscosity
• EKG: Conduction defects
• Measurement of respiratory excursion of chest wall: 5 cm maximal respiratory excursion of chest wall measured at fourth intercostal space
• 2.5 cm is virtually diagnostic of ankylosing spondylitis
• Wright-Schober test for lumbar spine flexion is abnormal or 5 cm.
- Mark the patient's back over the L5 spinous process and 10 cm above this point, then have the patient bend forward.The distance between the 2 marks should increase by 5 cm or more in normal persons.
Lab
• The HLA-B27 tissue antigen is present in 90% of White AS patients; there is a 5-8% incidence in the general population.
• ESR and CRP are elevated in the majority of the cases but correlate poorly with disease activity and prognosis. Mild elevation in serum IgA, creatine kinase, alkaline phosphatase, and complement may be seen.
• Absent rheumatoid factor
• Mild normochromic anemia (15%)
Imaging
• Sacroiliac joint early: Sclerosis on both sides of joint not extending >1 cm from articular surface = sacroiliitis
• Sacroiliac joint late
- Ankylosis of sacroiliac joint
- Osteopenia
• Spine
- "Squaring" of vertebral bodies and ossification of annulus fibrosis giving appearance of "bamboo spine"
- Ankylosis of facet joints
• Peripheral joint
- Symmetric erosive changes in larger joints
- Pericapsular ossification, sclerosis, loss of joint space
• Preferred position for imaging the SI joints with plain films is oblique projection. MRI of the SI joints may show increased signal from the bone and bone marrow suggesting osteitis and edema.
Diagnostic Procedures/Surgery
• Physical examination
• Radiographs: Sacroiliac joint films, lumbar spine series
• DEXA bone scan (high incidence of osteoporosis)
• MRI may show early enthesitis.
Pathological Findings
• Erosive changes coupled with new bone formation at the attachment of the tendons and ligaments to the bone resulting in ossification of periarticular soft tissues
• Synovial changes are indistinguishable from rheumatoid arthritis.
• Erosion of articular cartilage is less severe than in rheumatoid arthritis.
DIFFERENTIAL DIAGNOSIS
• Reactive arthritis
• Psoriatic arthritis
• Diffuse idiopathic skeletal hypertrophy (DISH)
• Spondylitis associated with inflammatory bowel disease
• Rheumatoid arthritis
TREATMENT
GENERAL MEASURES
• Appropriate healthcare: Outpatient
• Posture training and range of motion exercises for spine are essential.
• Firm bed
• Sleep in supine position without a pillow
• Breathing exercises 2-3  a day
• Smoking cessation
Activity
• Encourage active lifestyle. Swimming, tai chi, and walking are recommended.
• Avoid trauma/contact sports.
• Avoid prolonged standing.
SPECIAL THERAPY
Physical Therapy
Exercises to improve posture and flexibility
MEDICATION (DRUGS)
First Line
• NSAIDs provide symptomatic relief, usually rapidly.
- A dramatic response to NSAIDs can be diagnostic of AS.
• Selection is empiric, but traditionally indomethacin 50 mg t.i.d. or q.i.d. has been used.
• Intra-articular steroid injections may provide relief though systemic corticosteroids typically do not.
• Osteoporosis prophylaxis and treatment
• Injection of a long-acting corticosteroid into the sacroiliac joints may be beneficial in very symptomatic patients. Avoid systemic corticosteroids.
• Precautions
- All patients on long-term NSAIDs should have their renal function monitored.
- NSAIDs may aggravate peptic ulcer disease or cause gastritis.
- NSAIDs should be used with caution in patients with a bleeding diathesis or patients requiring anticoagulants.
- Refer to the manufacturer's profile of each drug for significant possible interactions.
Second Line
• Used when patients fail NSAIDs or become intolerant of them
• Sulfasalazine and methotrexate caused clinical improvement.
• Etanercept (anti-tumor necrosis factor alpha agent) showed rapid, significant, and sustained improvement and is now FDA-approved for AS. (2)[A]
• Infliximab can be efficacious and is also FDA-approved for AS. (4)[A]
• Thalidomide shows promise. (3)[C]
• Pamidronate may also help function and decrease disease activity. (3)[C]
SURGERY
• Total hip replacement should be considered to restore upright posture and to control pain in severe cases.
• Vertebral osteotomy can improve posture for those patients with severe cervical flexion.
FOLLOW-UP
DISPOSITION
Issues for Referral
Rheumatologists will be experienced in diagnosing and treating AS.
PROGNOSIS
• Unpredictable course
• Prognosis good if mobility and upright posture maintained
• Usually progressive disability
• No difference in overall mortality
COMPLICATIONS
• Spine
- Spinal fusion causing kyphosis
- Cervical spine fracture (high mortality rate)
- C1-C2 subluxation
- Cauda equina syndrome (rare)
• Peripheral joint ankylosis
• Pulmonary
- Restrictive lung disease
- Upper lobe fibrosis (rare)
• Cardiac
- Conduction defects
- Aortic insufficiency
- Aortitis
- Pericarditis
• Uveitis and cataracts
• Renal
- IgA nephropathy
- Amyloidosis (rare)
• Cutaneous LCV (rare)
• Gastrointestinal: Illeal and colonic mucosal ulcerations, mostly asymptomatic
PATIENT MONITORING
Visits every 6-12 months to monitor posture and range of motion
REFERENCES
1. Bennett DL, Ohashi K, El-Khoury GY. Spondyloarthropathies: Ankylosing spondylitis and psoriatic arthritis. Radiol Clin North Am. 2004;42(1):121-134.
2. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. 2002;346:1349-1356.
3. Davis JC Jr, Huang F, Maksymowych W. New therapies for ankylosing spondylitis: Etanercept, thalidomide, and pamidronate. Rheum Dis Clin North Am. 2003;29:481-494.
4. De Keyser F, Baeten D, Van den Bosch F, Kruithof E, Mielants H, Veys EM. Infliximab in patients who have spondyloarpthropathy: Clinical efficacy, safety, and biological immunomodulation. Rheum Dis Clin North Am. 2003;29(3):463-479.
5. Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Phys. 2004;69(12):2853-2860.