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Reactive and Undifferentiated Spondyloarthropathies… Ankylosing Spondylitis Ewa Olech, MD University of Nevada School of Medicine Division of Rheumatology Objectives Review epidemiology and genetic risks of SpA Examine pathophysiology and the underlying disease process Review clinical features, manifestations and comorbidities of SpA Discuss treatment options and management strategies The Spectrum of Spondyloarthritis Characteristics of the Spondyloarthritis Sacroiliac & spinal joint involvement Peripheral arthritis Enthesopathy Common spectrum of extra-articular features (especially mucocutaneous, ocular) Negative rheumatoid factor Familial clustering Association with HLA-B27 Potential infectious trigger HLA-B27 and the Seronegative Spondyloarthritides HLA-B27 Disorder frequency (%) Ankylosing spondylitis 95% Reactive arthritis 70% Psoriatic arthritis 25% Psoriatic spondylitis 60% Enteropathic arthritis 7% Enteropathic Spondylitis 70% Juvenile Spondyloarthropathy 70% Undifferentiated Spondyloarthropathy 70% Acute Anterior Uveitis 50% Most Common Seronegative Spondyloarthropathies 1. Ankylosing Spondylitis (AS) 2. Reactive Arthritis (ReA) 3. Enteropathic Arthritis (associated with IBD) 4. Psoriatic Arthritis (PsA) Pattern of Peripheral Synovitis in the Spondyloarthropathies Condition Pattern of Involvement Ankylosing • Asymmetric large-joint oligoarthritis, primarily lower Spondylitis extremities Reactive • Asymmetric large-joint oligoarthritis, primarily lower Arthritis extremities Enteropathic • Asymmetric large-joint oligoarthritis, primarily lower Arthritis extremities Psoriatic • Oligoarticular disease: Asymmetric large-joint Arthritis oligoarthritis, primarily lower extremities • Polyarticular disease: Symmetric polyarthritis involving large and small joints resembling RA • DIP joint disease: Associated with nail involvement • Arthritis mutilans: Severely destructive arthritis involving the hands with shortening of the digits Epidemiology of AS The incidence of AS underestimated1 Between 350,000 - 1 million Americans2,3 0.1% to 0.9% of the population worldwide4,5 Age of onset typically between 15 - 35 years1,2,3 2-3 times more frequent in men than in women6 The mean delay in the diagnosis: 5-11 years 1The Spondylitis Association of America. Available at: www.spondylitis.org. Accessed December 2,2004. 2Davis J. Semin Arthritis Rheum. 2004;34:668– 677. 3Newman PA, et al. Rheum Dis Clin Am. 2003;29(3):561– 571. 4Lawrence RC, et al. Arthritis Rheum. 1998;41(5):778– 99. 5Sieper J, et al. Ann Rheum Dis. 2002;61(suppl 3);iii8 –18. 6Khan MA. Ann Intern Med. 2002;136:896– 907. Enthesitis is the Hallmark of AS Enthesitis may affect: Capsules and intracapsular ligaments of large synovial (diarthrodial) joints and apophyseal joints Ligamentous structures of cartilaginous joints intervertebral discs manubriosternal joints symphysis pubis Ligamentous attachments spinous processes of the vertebrae illiac crests trochanters patellae calcanei clavicle Vernon -Roberts B. Spondyloarthropathies: AS -pathology. In: Hochberg M, et al., eds. Rheumatology 3rd ed. Edinburgh, Scotland: Mosby;2003:1205. Available at: www.rheumtext.com. Accessed December 6,2004. Enthesitis in Spondyloarthritis Enthesitis (Heel) MRI of Achilles Tendinitis Diffuse bone marrow edema of the calcaneous Swelling of the Achilles Tendon Fluid collection in retrocalcaneous bursa Inflammatory Enthesitis Subchondral bone inflammation and resorption Periosteal new bone formation McGonagle D. Arthritis Rheum. 1999. 42:1080-1086. Enthesitis Enthesitis of the Spine Occurs at capsular and ligamentous attachments Involvement of bony attachment of Anterior Longitudinal Ligament Ankylosing spondylitis: thoracic and lumbar vertebrae "squaring," osteopenia, and ossification Ankylosing spondylitis: lumbar vertebrae, bamboo spine Cervical Spine Normal Sacroiliitis Ankylosing spondylitis: advanced sacroiliitis Ankylosing spondylitis: advanced sacroiliitis (radiograph) AS: Sacroiliitis by MRI Thick Arrows: Subchondral marrow Thin Arrow: inflammation shown by Joint cavity increased MRI signal Maksymowych WP. Can Fam Physician. 2004;50:257 –262. Available at: http://www.cfpc.ca/cfp/2004/Feb/vol50 -feb- cme -3.asp. Accessed November 3,2004. Inflammatory versus Mechanical Low Back pain Inflammatory pain Mechanical pain Age at onset <40 yr Any age (usually later) Type of onset Insidious Acute Symptom duration >3 mo <4 wk Morning stiffness >30 min <30 min Nocturnal pain Common Absent Effect of exercise Improvement Exacerbation Sacroiliac joint Frequent Absent tenderness Back mobility Loss in all planes Abnormal flexion Chest expansion Often decreased Normal Neurologic deficits Unusual Possible Clinical Features • Chronic inflammatory low back pain and stiffness1 – Buttock pain – Symptoms worsen after prolonged periods of inactivity ('gel phenomenon') – Symptoms improved with exercise / hot shower – Some patients may wake-up at night to exercise or move about for a few minutes before returning to bed • Peripheral joint involvement2 – Synovitis – Dactylitis – Enthesitis 1Khan MA In: Hochberg M, et al., eds. Rheumatology 3rd ed. Edinburgh, Scotland: Mosby;2003:1161– 1170. 2Keat A. In: Klippel JH, ed. Primer On The Rheumatic Diseases. Clinical Features • Limitation of spinal mobility and chest expansion • Characteristic radiographic findings late in disease • Constitutional symptoms may occur in early stages – anorexia – malaise – weight loss – low-grade fever – fatigue • Extraarticular manifestations Khan MA. Spondyloarthropathies: clinical features of AS. In: Hochberg M, et al., eds. Rheumatology 3rd ed.. Extraarticular Manifestations of AS Eyes (Acute Anterior Uveitis) Lungs (Restrictive Lung Disease, Apical Fibrocystic Disease) Heart (Aortic Insufficiency, Heart Block) Kidneys (Amyloidosis) Gut Skin (Inflammatory Bowel Disease, (Psoriasis & Nail Changes) Microscopic Inflammatory Lesion) Osteoporosis Dactylitis Khan MA. Ann Intern Med. 2002;136:896 –907. Acute Anterior Uveitis Most common extraarticular complication (approximately 1/3 of patients with AS) Unilateral, asynchronous with arthritis flares Pain, redness, lacrimation, photophobia, blurred vision Untreated can lead to vision loss Anterior Uveitis Pt with AS, red, sore, gritty eyes, blurred vision should get an urgent ophthalmologic examination Patient Case 26 yrs old Caucasian male C/o inflammatory back pain since 20 y/o Recently bilateral heel pain Constitutional sx: fatigue, low grade fever, weight loss Labs: HLA B27 – positive Elevated CRP Sacroiliitis – bilateral grade 3 changes AS: Modified New York Criteria 1. Low back pain >3 months • Improved with exercise Definite AS equals: • Not relieved by rest at least 1 criteria 2. Limited lumbar motion 3. Reduced chest expansion PLUS 4. Bilateral grade ≥2 sacroiliitis on x-ray Either 4 or 5 5. Unilateral grade 3 to 4 on sacroiliitis on x-ray van der Linden S, et al. Arthritis Rheum. 1984;27:361 –368. Ankylosing spondylitis: postural changes Ankylosing spondylitis: ankylosis, lumbar spine Schoeber’s Wall to Occiput Chest Expansion Progression of Deformities TREATMENT OF ANKYLOSING SPONDYLITIS Treatment Exercise NSAIDS Traditional DMARDs – peripheral arthritis Biologics Surgery 42 Structures of TNF Inhibitors Etanercept Infliximab Adalimumab (Humira®), Certolizumab pegol (Enbrel®)1 (Remicade®)2 Golimumab (Simponi®) (CIMZIA®)5 1 Fab′ Receptor Fab′ IgG1 IgG1 Fc Fc Fc- PEG free Recombinant Recombinant Recombinant Recombinant receptor/Fc fusion human/mouse human IgG1 humanized PEGylated protein chimeric IgG1 IgG1 Fab’ fragment Monoclonal antibody 42 Approved anti-TNF agents for Ankylosing Spondylitis Therapeutic Trade Mechanism of Usual Maintenance Route Agent Name Action Dose Infliximab Remicade TNF-α 5–10 mg q 4 - 8 wks IV inhibitor Etanercept Enbrel TNF-α 50 mg weekly SQ inhibitor Adalimumab Humira TNF-α 40 mg q 2 wks SQ inhibitor Golimumab Simponi TNF-α 50 mg q 4 wks SQ inhibitor Certolizumab Cimzia TNF-α 200 mg q 2 wks or SQ Pegol inhibitor 400 mg q 4 wks THANK YOU .
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