lect 36 - musculoskeletal diseases II_SM.pdf

Spondyloarthropathy • Family of inflammatory rheumatic diseases that cause arthritis • They involve the “entheses” – where ligaments and tendons attach to bones • Includes: – Psoriatic arthritis – Ankylosing spondylitis (AS) Environmental trigger Susceptible host – Reactive arthritis – Enteropathi...

Spondyloarthropathy • Family of inflammatory rheumatic diseases that cause arthritis • They involve the “entheses” – where ligaments and tendons attach to bones • Includes: – Psoriatic arthritis – Ankylosing spondylitis (AS) Environmental trigger Susceptible host – Reactive arthritis – Enteropathic arthritis associated with IBD (e.g., Crohn’s disease, ulcerative colitis) • Manifestations can overlap. Shared tendency to develop inflammation and calcification of entheses and new bone formation • Other spondyloathropathies share association with HLA-B27, but lower incidence than with AS Disease Spondyloarthropathies and HLA-B27 Molecular Mimicry? Population or Disease Entity * * * HLA-B27 –Positive Healthy whites 8% Healthy African Americans 4% Ankylosing spondylitis (whites) 92% Ankylosing spondylitis (African Americans) 50% Reactive arthritis 60-80% Psoriasis associated with spondylitis 60% IBD associated with spondylitis 60% Isolated acute anterior uveitis 50% Undifferentiated spondyloarthropathy 20-25% Psoriatic arthritis 10-30% Psoriatic Arthritis The Start: Psoriasis • Silvery scale on extensor surfaces (esp. knees and elbows) • Very common – prevalence of 1-8.5% of adults Pathophysiology of Psoriatic Arthritis • Inflammatory arthritis – progressive disease with joint erosion • Seen in up to 30% of psoriasis patients (onset of psoriasis 1st) ‒ Median onset of psoriasis – 27-31 yoa ‒ Median onset of arthritis – 38-52 yoa ‒ 15% of patients have arthritis first, then psoriasis • Strong association w/ HLA-Cw6 – Early onset of psoriasis and more extensive/severe disease – Also, association of articular symptoms to HLA-B proteins (27, 38, 39) • Environmental trigger – Possible association w/ streptococcal infection • Cell-mediated response – CD4, CD8, macs, PMNs Signs and Symptoms of Psoriatic Arthritis Spine and Digits • Enthesitis – common presenting symptom – Most common at Achilles and plantar fascia insertion • Dactylitis – “sausage” shaped fingers or toes – Common presenting symptom • Tenosynovitis • Asymmetric oligo-arthritis • Spondylitis • Morning stiffness – usually lasting more than 30 minutes, improves with activity and worsens with immobility Psoriatic Arthritis: Patterns of Joint Involvement 1. 2. 3. 4. 5. Symmetric polyarthritis (45%) Asymmetric mono/oligo-arthritis (30%) Distal interphalangeal (DIP) joint involvement (5%) Axial spondylitis/sacroilitis (5%) Arthritis mutilans (<5%) Imaging in Psoriatic Arthritis (PsA) X-ray: Bony erosion and resorption together cause “pencil in cup” deformity, joint space narrowing, entheseal sites (bony spurs, periostitis) Extra-Articular Signs and Symptoms of PsA • Plaque psoriasis (psoriasis vulgaris) – most common • Nail changes – Nail pitting, onycholysis, nail bed hyperkeratosis, and splinter hemorrhages • Fatigue • Uveitis or iritis – rare Diagnosing Psoriatic Arthritis There is no specific lab test. • Usually RF-negative, but a few pts may be positive for RF, anti-CCP, or ANA • Nonspecific signs of inflammation – ESR and CRP • X-rays – “gold standard” to assess bony changes CASPAR = Classification of Psoriatic Arthritis Study Group Criteria • Skin Psoriasis ‒ Present – 2 points ‒ Previously present by history – 1 point ‒ Family history of psoriasis – 1 point • Nail lesions (onycholysis, pitting) – 1 point • Dactylitis (onycholysis, pitting) – 1 point • Negative rheumatoid factor (RF) – 1 point • Juxta-articular bone formation on radiographs – 1 point Treating Psoriatic Arthritis • DMARDs (methotrexate, cyclosporine, sulfasalazine, leflunomide) • Biologics also available – etanercept (Enbrel™), infliximab, adalimumab (Humira™), etc. Which One Is It? https://www.semanticscholar.org/paper/Psoriatic-arthritis%3A-state-of-the-art-review-Coates-Helliwell/bcefecc5023211ff3fa4345ddc99a33fb52b94bb Ankylosing Spondylitis The Basics of Ankylosing Spondylitis (AS) • Chronic systemic inflammatory disease of the axial skeleton with involvement of peripheral joints and non-articular structures • Mainly affects the sacroiliac joint and pelvis, causing eventual fusion of the spine • If the spine completely fuses, “bamboo spine” • Enthesis = the site of attachment of a muscle or ligament to bone https://images.ctfassets.net/oc83wx5cwffk/spu_wysiwyg_fid36479_asset/3c348576e94e34a032e5985fa7 9237e2/ankylosing_spondylitis11222989_M.jpg https://prod-imagesstatic.radiopaedia.org/images/56055054/ankylosing_spondylitis_jumbo.jpeg Epidemiology of AS • Prevalence in US ~0.5% (varies w/ prevalence of HLA-B27 gene) • Male:female = 3:1 • Onset – late teens to 40 years; long delay in diagnosis • Racial difference due to gene distribution ‒ 90% of white pts with AS have HLA-B27 ‒ <1% of African blacks and Japanese are HLA-B27+ • Image: Imagine Dragon’s Dan Reynolds. He was diagnosed when he was 20 years old. • https://www.practicalpainmanagement.com/patient/conditions/low-back-pain/imagine-dragons-dan-reynoldsbreaks-his-silence-about-ankylosing (Tells about his presentation) Pathophysiology of AS Enthesitis with chronic inflammation of vertebrae, esp. sacroiliac (SI) joint • TNF-α and IL-1 contribute to disease pathogenesis • More of a cell-mediated response (CD4 and CD8) than of auto-antibodies • Inflammation causes release of matrix metalloproteinases (MMPs) • MMPs then erode the fibrocartilage • As repair begins, scar tissue ossifies, calcifies, and fuses the joint. https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs00281-021-00838-z/MediaObjects/281_2021_838_Fig1_HTML.png Signs and Symptoms of AS • Early symptoms – Pain and stiffness, usually in the middle or lower back, mainly in SI joint – prevailing diagnostic feature o Inflammatory back pain is the most common symptom and the first manifestation in ~ 75% of patients o Morning stiffness – min 30 min. (as long as 3 hrs) o Worse at night o No improvement with rest o Chronic = > 3 mo – Usually no swelling, except at Achilles insertion – Extra-articular signs/symptoms: uveitis, IBD, psoriasis • Later symptoms – Fusion of vertebrae = bamboo spine – Lose normal posture Diagnosing Ankylosing Spondylitis • Diagnosis based on history + physical exam + X-rays • Difficult to diagnose • Usually, 8-11 yr lag time between onset of symptoms and diagnosis • Imaging – X-ray of pelvis or MRI if X-rays are non-diagnostic • Lab – no lab test is diagnostic – HLA-B27 may be helpful – ESR and/or CRP – general markers of inflammation The Picture of Ankylosing Spondylitis Grade 0 – normal Grade 4 –complete fusion Treatment of Ankylosing Spondylitis • Goal: maintain function, prevent complications, relieve symptoms • NSAIDs – first line • Analgesia – Opioid analgesics – minimize use, but may use as required – Local corticosteroid injections – may be helpful – Systemic corticosteroids – may control flares, but should use only short-term • TNF inhibitors such as etanercept, infliximab, golimumab, adalimumab • Joint replacement, especially if it affects knees or hips • Non-pharmaceutical – exercise, physical therapy, STOP SMOKING (see notes)