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Seronegative Spondyloarthropathie s Internal Medicine/Pediatrics Noon conference series June 1, 2006 Back to basics The skeleton Axial skeleton Skull Vertebral column Vertebrae Sacrum Coccyx Ribs Sternum Appendicular skeleton Girdles Extremities Back to basics Articulations Diarthrosis (moveable) Synarthrosis (immoveable) Majority of articulations Contiguous bones are covered by cartilage, connected by ligaments, and have an interposing synovial sac Contiguous bones are in direct contact without cartilage, syovium, or ligaments Amphiarthrosis (sort of moveable) Characteristics of both diarthrosis and synarthrosis Contiguous surfaces are either: Connected by fibrocartiganeous disks (vertebral joint) Covered by fibrocartilage and partial synovium, and attached by external ligaments (sacroiliac joint) Back to basics Enthesis Enthesis is the site of bony attachment of Tendon Ligament Cartilage Joint capsule Fascia Seronegative spondyloarthropathies Comprise these conditions… Ankylosing spondylitis (the prototype) Psoriatic arthritis Reactive arthritis Formerly called Reiter’s syndrome) Enteropathic arthritis Undifferentiated spondyloarthropathy Mnemonic is PURE-A (sort of like purée) Why are these diseases classified together? Well, because they share these characteristics… HLA-B27 association Enthesitis (both juxtaärticular and extraärticular) Axial skeleton arthritis (generally secondary to juxtaärticular enthesitis) Peripheral arthritis (generally a synovitis) Spondylitis (inflammation of vertebral bodies) Sacroiliitis (inflammation of sacroiliac joint) Asymmetric (cf rheumatoid arthritis) Extraärticular manifestations (besides enthesitis) Seronegativity Rheumatoid factor and ANA negative Why are these diseases classified together? HLA-B27 association Ankylosing spondylitis: 95% Ethnically matched controls: 8% Reactive arthritis: 70% Enteropathic arthritis: 50% Psoriatic arthritis: 35% Why are these diseases classified together? Enthesitis Inflammation of an enthesis Principal pathogenetic mechanism in spondyloarthropathy Pathogenesis CD8 T cells infiltrate entheses Activated macrophages release cytokines (eg TNF) Fibroblasts synthesize new collagen (cf rhematoid arthritis!!) New bone formation results Clinical Axial skeleton arthritis (see later) Enthesopathy at other sites Calcaneal spurs at plantar fascia insertion Spurs at Achilles tendon insertion Manifests as extraärticular or juxtaärticular bony tenderness Why are these diseases classified together? Axial skeleton arthritis Arises from enthesitis Includes spondylitis and sacroiliitis Spondylitis CD8 T cells invade the junction of the annulus fibrosis and the vertebral body (an enthesis) Annulus fibrosis is replaced by bone (syndesmophytosis) Vertebral bodies assume a square shape, and ultimately a bamboo spine Sacroiliitis CD8 T cells invades the subchondral area at the junction of the bones and the cartilage (an enthesis) Cartilage on iliac side is replaced by bone, obliterating the jont space and hardening the joint Ankylosing spondylitis Inflammatory back pain Inflammatory back pain requires 4 of these 5 criteria (serves as a screening tool for AS) Young onset ( 40 years) Morning stiffness ( 30 minutes) Chronic ( 3 months) Activity improves the pain (rest does not) Insidious (not acute) (mnemonic is YMCA-I) Diffuse lumbar or gluteal, not focal or radicular Cf focal pain of disk herniation Ankylosing spondylitis Other clinical (besides back pain) Restriction of lumbar movement Anterior uveitis (iritis or iridocyclitis) (25%) Shober’s test – mark the patient’s back at the level of the posterior iliac spine. Place one finger 5 cm below this mark and a 2nd finger 10 cm above this mark. Patient is instructed to touch his toes. If the distance between finegrs increases < 5 cm, lumbar flexion is limited. Acute eye pain Increased lacrimation Photophobia Blurred vision Aortitis with fibrosis Aortic insufficiency Third degree heart block (5%) Ankylosing spondylitis Radiographic evaluation Sacroiliac joints Grade 0 Normal Grade 1 Suspicious changes Grade 2 Minimal abnormality – small localized areas with erosion or sclerosis without alterations in joint width Grade 3 Unequivocal abnormality – moderate or advanced sacroiliitis with 1 of the following: erosions, sclerosis, widening, narrowing, or partial ankylosis Grade 4 Severe abnormality – total ankylosis Ossification of SI joint space Bamboo spine Ankylosing spondylitis Modified New York Diagnostic Criteria Low back pain 3 months improved by exercise and not relieved by rest Limitation of lumbar spine in sagittal and frontal planes Chest expansion reduction relative to normal values corrected for age and sex (costovertebral ankylosis, 25%) Radiographic criteria of sacroiliitis Bilateral grade 2-4 OR Unilateral grade 3-4 Ankylosing spondylitis is defined by the presence of either radiographic criterion PLUS any clinical criterion Reactive arthritis Interesting historical backdrop In 1916, Hans Reiter reported Reiter’s syndrome: a triad of nongonococcal urethritis, conjunctivitis, and arthritis that occurred in a young German officer following an episode of bloody dysentery Subseqently, more cases were reported following enteric infections OR venereally acquired genitourinary infections. In 1967, the term reactive arthritis was applied to similar cases following Yersinia gastroenteritis The two terms should be considered synonomous The term reactive arthritis is increasingly preferred Reactive arthritis Pathogenesis Clinical syndrome triggered by specific etiologic agents in a genetically susceptible host Follows 1-4 weeks after a Urogenital infection (affects principally men) Usually C. trachomatis Enteric infection (affects both genddrs equally) Salmonella Shigella Campylobacter Yersinia Reactive arthritis Clinical Peripheral arthritis Asymmetric additive oligoarthritis (usually) Synovitis Warm Edematous Tender Pain with active or passive movement Usually lower extremity joints (knee, ankle, subtalar) Conjunctivitis Reactive arthritis Clinical Nongonococcal urethritis Occurs in postenteric or postvenereal disease When present, is usally the first symptom In men Mild dysuria Mucopurulent urethral discharge May present as prostatitis or epididymitis In women When it occurs in postvenereal disease, C. trachomatis is often the etiology Dysuria Purulent vaginitis or cervicitis with vaginal discharge Asymptomatic urethritis often features sterile pyuria Reactive arthritis Clinical (continued) Keratoderma blenorrhagica A papulosquamous skin rash Comprises vesicles that become hyperkeratotic, forming crusts before disappearing Palms/soles Penis (causing circinate balanitis Oral ulcers (ususally shallow and painless) Inflammatory back pain (50% of patients) Enthesitis (40%) Dactylitis (40%) Anterior uveitis (20% of patients) Reactive arthritis Keratoderma blenorrhagica Reactive arthritis Evaluation Synovial fluid analysis Pleocytosis (5 000 to 50 000 WBC/mcL) with polymorphonuclear cell predominance Protein levels Glucose normal Cf reduced glucose level in true septic arthritis Gram stain and culture are sterile Urethral or cervical smears in patients with clinical urethritis C. trachomatis N. gonorrhoeae Enteropathic Arthritis Clinical Affects 10-20% of patients with inflammatory bowel disease (IBD) Peripheral arthritis affects 10-20% of IBD patients Generally affects knees, ankles, and feet Always indicates active IBD Radiographic axial arthritis affects 10% of IBD patients Frequently asymptomatic Independent of bowel inflammation Why are these diseases classified together? Treatment Nonsteroidal antiinflammatory agents Disease modifying anti-rheumatic drugs (DMARDs) Methotrexate: inhibits recruitment of CD4 and CD8 T cells Tumor necrosis factor antagonists Indamethacin Infliximab: a monoclonal antibody that binds to TNF and inhibits binding of TNF to its receptor Etanercept: similar emchanism to infliximab For axial arthritis, exercises to maintain posture and flexibility