ANKYLOSING SPONDYLITIS BASICS DESCRIPTION A chronic, usually progressive, condition in which inflammatory changes and new bone formation

occurs at the attachment of tendons and ligaments to bone (enthesopathy) Sacroiliac joint involvement is the hallmark of ankylosing spondylitis (AS) with variable degrees of spinal involvement. However, 20-30% of patients also have larger peripheral joint involvement System(s) affected: Musculoskeletal Genetics: Familial clustering and higher than expected frequency of HLA-B27 tissue antigen. Frequency of HLA-B27 in North American Caucasians = 7%. Frequency of HLAB27 in African Americans = 1-2%. Incidence/Prevalence in USA: 0.5-5 per 1000 in white males Less common in women and Blacks Predominant age: Usually symptoms begin in early twenties Onset of symptoms - rarely occurs after age 40 Predominant sex: Male > Female (3:1) SIGNS & SYMPTOMS Subgluteal or low back pain and/or stiffness Insidious onset Duration greater than 3 months Morning stiffness Frequently awaken at night to walk off stiffness Improvement in stiffness with activity Increased symptoms with rest Pleuritic chest pain is often an early feature Hip, shoulder, or knee complaints Diminished range of motion in the lumbar spine in all three planes of motion Loss of lumbar lordosis Thoracocervical kyphosis (rarely occurs before ten years of symptoms) Aortic root dilatation (1%) Aortic regurgitation murmur (1%) Acute anterior uveitis (2530%) Osteoporosis Constitutional symptoms (fatigue, weight loss, lowgrade fever) Plantar fasciitis CAUSES Unknown RISK FACTORS HLA-B27 (1-7% 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

DIAGNOSIS LABORATORY HLA-B27 tissue antigen is present in 90% of white AS patients compared to 5-8% incidence in general population Erythrocyte sedimentation rate (ESR) and CRP are frequently elevated 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%) Drugs that may alter lab results: N/A Disorders that may alter lab results: N/A PATHOLOGICAL FINDINGS Erosive changes coupled with new bone formation at attachment of tendons and ligaments to 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. SPECIAL TESTS Synovial fluid - mild leukocytosis, decreased viscosity EKG - conduction defects Measurement of respiratory excursion of chest wall - less than 5 cm maximal respiratory excursion of chest wall measured at fourth intercostal space. Less than 2.5 cm is virtually diagnostic of ankylosing spondylitis. Wright-Schober test for lumbar spine flexion is abnormal IMAGING Sacroiliac joint early - sclerosis on both sides of joint not extending more than 1 cm from articular surface 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 Physical examination Radiographs - sacroiliac joint films, lumbar spine series DEXA bone scan (high incidence of osteoporosis) TREATMENT APPROPRIATE HEALTH CARE Outpatient GENERAL MEASURES Posture training and range of motion exercises for spine are essential Firm bed Sleep in prone position or supine without a pillow Breathing exercises 2-3 times/day Swimming Physical therapy Stop smoking, if a smoker Avoidance of trauma/contact sports Avoidance of prolonged standing SURGICAL MEASURES Total hip replacement should be considered to restore upright posture and to control pain. Wedge osteotomy is indicted in those patients who develop severe flexion deformities. ACTIVITY Encourage active lifestyle DIET No special diet

MEDICATIONS DRUG(S) OF CHOICE Nonsteroidal anti-inflammatory drugs provide symptomatic relief Selection is empiric, but traditionally indomethacin 50 mg tid or qid has been used Osteoporosis prophylaxis and treatment Injection of a long-acting corticosteroid into the sacroiliac joints may be beneficial in very symptomatic patients. Avoid systemic corticosteroids. Contraindications: See Precautions Precautions: All patients on long term NSAIDs should have renal function monitored NSAIDs may aggravate peptic ulcer disease or cause gastritis Dont use NSAIDs for patients with a bleeding diathesis or patients requiring anticoagulants Significant possible interactions: Refer to manufacturers profile of each drug ALTERNATIVE DRUGS Etanercept (anti-tumor necrosis factor alpha agent) showed rapid, significant and sustained improvement Thalidomide shows promise Infliximab may be efficacious Sulfasalazine and methotrexate may be helpful in some patients. FOLLOWUP PATIENT MONITORING Visits every six to twelve months to monitor posture and range of motion PREVENTION/AVOIDANCE N/A POSSIBLE COMPLICATIONS Spine: Pseudarthrosis, cervical spine fracture (high mortality rate), C1-C2 subluxation, spondylodiscitis, cauda equina syndrome (rare) Peripheral joint ankylosis Pulmonary: Restrictive lung disease, diaphragmatic breathing, upper lobe fibrosis (rare) Cardiac: Conduction defects, aortic insufficiency (2%), aortitis, pericarditis Uveitis and cataracts Renal: IgA nephropathy, amyloidosis (rare) Cutaneous LCV (rare) Gastrointestinal: illeal and colonic mucosal ulcerations, mostly asymptomatic EXPECTED COURSE/PROGNOSIS Unpredictable course Prognosis good if mobility and upright posture maintained. Usually progressive disability. No difference in overall mortality REFERENCES van der Linden S, van der Heijde D. Ankylosing spondylitis. Clinical features. Rheum Dis Clin North Am 1998;24(4):663-76, vii Klippel J, ed. Primer on the Rheumatic Diseases. 12th Ed. Atlanta, Arthritis Foundation, 2001 Ruddy S, Kelley S. Textbook of Rheumatology. 6th ed. Philadelphia: WB Saunders Co; 2001 Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002;346(18):1349-56 Davis JC Jr, Huang F, Maksymowych W. New therapies for ankylosing spondylitis: etanercept, thalidomide, and pamidronate. Rheum Dis Clin North Am 2003;29(3):481-94