Medical Pathology: Arthropathies PDF

Medical Pathology: Arthropathies CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — Understand pathophysiology and clinical findings of non-inflammatory arthropathies. ¡ Osteoarthritis — Understand pathophysiolo...

Medical Pathology: Arthropathies CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — Understand pathophysiology and clinical findings of non-inflammatory arthropathies. ¡ Osteoarthritis — Understand pathophysiology and clinical findings of inflammatory arthropathies. ¡ Rheumatoid arthritis, JIA, Gout, Spondylarthropathies — Know principles of discussed lab tests and how to use them clinically to diagnose arthropathic conditions. NBEO Outline — Musculoskeletal System ¡ 1. Epidemiology ¡ 2. Symptoms and signs of the various arthritic syndromes (e.g., JRA, RA, ankylosing spondylitis) ¡ 3. Diagnostic testing and imaging ¡ 4. Pathophysiology and diagnosis Arthropathies — Defn: Diseases of the joints ¡ Non-inflammatory arthropathies (arthrosis) ÷ Osteoarthritis ¡ Inflammatory arthropathies (arthritis) ÷ Rheumatoid arthritis ÷ Juvenile idiopathic arthritis ÷ Gout ÷ Spondyloarthropathies Review: Anatomy/Physiology of Joints — 3 main types: ¡ ¡ ¡ Fixed/Fibrous: skull Cartilaginous: intervertebral discs Synovial*: knee, elbow — Articular cartilage ¡ Avascular connective tissue surrounding the ends of bones — Joint capsule ¡ Membranous sac that encloses the joint — Synovium ¡ ¡ Thin membrane inside the joint capsule Secretes synovial fluid — Synovial fluid ¡ ¡ Lubricates the joint Nourishes the cartilage — Ligaments ¡ ¡ Bone to bone Stabilize the joint — Tendons ¡ ¡ Muscles to bones Transmit force from muscles — Muscles ¡ Move the joint Arthritis — *Inflammation of one or more joints ¡ ¡ >50 million diagnoses in the US Very common disability ÷ >21 million adults (9% US population) — Common symptoms: ¡ ¡ ¡ ¡ ¡ Pain Stiffness Decreased range of motion Swelling Redness — Systemic associations possible: ¡ ¡ ¡ ¡ Autoimmune (ie. SLE) Infectious (ie. gonorrhea, chlamydia, shigella) Biochemical (ie. gout) Others possible… Osteoarthritis Osteoarthritis — Defn: *Mechanical breakdown of articular cartilage ¡ *Most common arthropathy ÷ 10-13% US population (~30 million) — Risk Factors: ¡ *Obesity (36.5% USA is obese) ÷ 69% knee replacements in USA 2’ obesity Autoimmune diseases ¡ Increased age; F>M ¡ Previous joint injury ¡ Repetitive motion — Signs and Symptoms: ¡ Stiffness after a period of immobility ¡ Joint swelling and/or joint pain ¡ Crunching feeling or the sound of bone rubbing on bone ¡ Osteoarthritis — Joints typically affected: ¡ ¡ ¡ ¡ — Lifetime Risk of OA ¡ — Knee = 46%; Hip = 25% Diagnosis ¡ — **Knees (37% >60 yo) *Hips *Hands Spine X-ray/CT/MRI Treatment ¡ ¡ ¡ ¡ ¡ ¡ Exercise (low impact) Weight loss Analgesics Anti-inflammatories Joint Replacement Surgery Physical therapy (PT) Rheumatoid Arthritis Rheumatoid Arthritis — *Autoimmune destruction of the joints ¡ Trigger à idiopathic ÷ Genetics? Infection? 1-2% of adult population ¡ F>M (3X) ¡ — Average onset = 20-30 yo ¡ Peaks between 30-55 yo ¡ Sn/Sx: mild to severe possible ¡ Periods of remission and exacerbation ¡ Symptoms lessen during pregnancy (70% cases improve) Rheumatoid Arthritis — Complications: ¡ Destroys and distorts joints over time ¡ Reduces mobility and QOL ¡ Reduces life expectancy Ulnar deviation Severe Rheumatoid Factor (RF) — RF = an IgM Anti-IgG autoantibody ¡ Forms immune complexes à deposit in joints ¡ Inflammatory cells accumulate at sites of deposition ¡ Chronic inflammation à angiogenesis ¡ “Pannus” covers the articular cartilage ¡ Causes bone destruction and joint deformity Labwork: Rheumatoid Arthritis Diagnosis — *Rheumatoid factor (RF) ¡ IgM àNonspecific marker for RA; also (+) in SLE, Sjogrens, TB, etc. ¡ 75% of RA patients ¡ High titers = more severe disease — *Anti-cyclic citrullinated peptide (CCP) antibody ¡ IgG à Positive in 64-89% of RA patients ¡ More sensitive and specific than RF ¡ Progression/prognosis worse if (+)CCP — Antinuclear antibody (ANA) ¡ IgG à 20% of RA patients ¡ Titer is lower than in SLE — HLA-DR1 and HLA-DR4 ¡ 60-70% in RA patients Rheumatoid Arthritis Treatment — Medication ¡ Disease modifying anti-rheumatic drugs (DMARDs) Methotrexate ÷ Hydroxychloroquine ÷ Gold salts ÷ ¡ Biologics ÷ ¡ Rituximab, Infliximab Anti-inflammatories ÷ Steroids, NSAIDs — Physical therapy — Exercise — Surgery — *Ocular Manifestations: ¡ Episcleritis, Scleritis, Iritis, PUK Ocular chrysiasis Juvenile Idiopathic Arthritis Juvenile Idiopathic Arthritis — Formerly known as “juvenile rheumatoid arthritis” (JRA) ¡ JRA ≠ Adult RA — *Most common childhood arthritis — Autoimmune disorder targeting synovium ¡ Chronic inflammation leads to joint damage ¡ Affects ~1 in 1000 children ¡ F>M ¡ *Onset before 16 yo — Signs and symptoms: ¡ Joint stiffness/pain ¡ Limited range of motion ¡ Warm, swollen, or red joints ¡ Child may stop using limb or may limp Juvenile Idiopathic Arthritis — Systemic symptoms ¡ Fever, usually high fevers every day ¡ Rash that comes and goes with the fever ¡ Pale skin ¡ Malaise ¡ Lymphadenopathy — Ocular manifestations ¡ **Anterior uveitis** (~12% of all JIA cases) It is recommended that all children with JIA be screened for iritis ÷ **Most common cause of uveitis in pediatric age group ÷ ¡ SE: Cataracts from steroids Juvenile Idiopathic Arthritis — Diagnosis ¡ History & examination ¡ Labwork: Same as adult RA ¡ HLA-B27 à predicts more severe disease if positive too — Treatment ¡ Same as adult RA — Prognosis is good with early Dx and Tx Gout Gout — Acute episodes of painful joint inflammation ¡ *Cause: Uric acid buildup in any joint; (deposits à tophi) ¡ Reduced kidney clearance > increased production ÷ 90% vs. 10% — 3 million cases in US ¡ M>F ¡ AA>Caucasian (2X) ¡ Onset 40-50 yo — Signs and symptoms ¡ Sudden onset of pain Usually the proximal joint of the great toe in 50% of cases ÷ Initial pain lasts 12-48 hours ÷ ¡ Edema and erythema Gout Excess uric acid Supersaturation Crystal formation Joint degradation — Dietary sources of purines ¡ Organ meats ¡ Shellfish/Seafood ¡ Alcohol ¡ Soda drinks Gout — Risk factors ¡ Age ¡ Sex ¡ Genetics ¡ Renal disease ¡ Diet ¡ Obesity ¡ Systemic disease ÷ HTN/DM/Hyperlipidemia — Diagnosis ¡ Serology (>7 mg/dL) ¡ Urinalysis ¡ Synovial fluid aspiration — Treatment (Goal: <6 mg/dL) ¡ Acute Anti-inflammatories ÷ Colchicine ÷ ¡ Prophylactic Allopurinol ÷ Probenecid ÷ ¡ Lifestyle modifications Proper hydration ÷ Decrease alcohol intake ÷ Weight loss ÷ Dietary changes ÷ Spondylarthropathies Spondylarthropathies — Types: 1. 2. 3. 4. 5. ¡ Ulcerative Colitis Crohn’s/Inflammatory Bowel Disease-associated SpA Reactive Arthritis Ankylosing Spondylitis Psoriatic Arthritis Acronym: “UCRAP” Spondylarthropathies — Defn: Diverse group of chronic inflammatory conditions ¡ *Affect axial and peripheral joints mainly ¡ “Seronegative” for RF and ANA — Common features: ¡ Inflammatory back pain ¡ Enthesitis ÷ ¡ Inflammation at sites where tendons, ligaments, and joint capsule fibers attach to bone Extra-articular manifestations Psoriasis ÷ Anterior uveitis/iritis ÷ Inflammatory bowel disease ÷ HLA-B27 Testing — Class I major histocompatibility complex molecule — Present in only 1.4-8.0% of the general population ¡ Whites>non-whites — **Strongly associated with all SpA*** ¡ ~70% of all individuals w/ SpA carry the HLA-B27 gene ¡ Inflammatory bowel disease ÷ ¡ ¡ ¡ (Ulcerative Colitis & Crohn’s) Reactive Arthritis Ankylosing spondylitis Psoriatic arthritis } “UCRAP” 1. Inflammatory Bowel Disease • See GI Tract 2 Lecture — Arthritis occurs in 25% of patients — 50–60% of patients with IBD and spondylitis will be HLA-B27 positive — *Acute anterior uveitis/iritis occurs: ¡ ¡ 5-10% of patients with Ulcerative Colitis 2.5% of patients with Crohn’s Disease — Other rare ocular findings seen with IBD include: ¡ Episcleritis ¡ Scleritis ¡ Optic neuritis ¡ Retinal vasculitis 2. Reactive Arthritis (Reiter’s Syndrome) — Inflammatory arthritis that is post genitourinary or gastrointestinal infection ¡ ¡ ¡ ¡ Annual prevalence of 1-7% Whites>non-whites Onset 20-50 yo Men>Women ÷ ÷ Equal for enteric 9X greater in men for STD — Causative agents ¡ ¡ ¡ ¡ ¡ *Chlamydia (36-61%) Salmonella (6-30%) Shigella Campylobacter Gonorrhea Mucopurulent conjunctivitis 1. ÷ Usually within several days to weeks — Type III hypersensitivity ¡ — Classic triad of symptoms: ÷ “Can’t see” Conjunctivitis and/or iritis usually Non-specific urethritis 2. ÷ ÷ “Can’t pee” Discharge and/or dysuria Arthropathy 3. ÷ ÷ “Can’t climb a tree” Involves the lower extremities — Triad is found in ~33% cases — Acute anterior uveitis occurs in about 5-10% of patients and sometimes becomes chronic. Reactive Arthritis — Diagnosis ¡ **HLA-B27 ÷ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ 65-95% positive Joint X-rays CBC CRP ESR RF ANA Serum creatinine Synovial analysis Culture — Treatment ¡ ¡ ¡ ¡ ¡ Spontaneous resolution Anti-inflammatories Antibacterials DMARDs Physical therapy — 80-85% of cases resolve w/ no long-term complications ¡ ~15-20% of cases can develop chronic arthritis 3. Ankylosing Spondylitis — “inflamed, fused spine” — Arthritis of the spinal column ¡ 0.25% prevalence ¡ Chronic and progressive ¡ M > F (3X) ¡ Whites>non-whites ¡ Onset usually 15-35 yo — Etiology is unknown ¡ Family history is a risk factor ¡ Possible environmental trigger? Infection? — Signs and symptoms ¡ *Chronic pain of the lower spine and buttocks ÷ ÷ ¡ ¡ Sacroillitis Spondylitis Morning stiffness Bamboo spine (fused) ÷ Inflammation à erodes cartilage à allows access to bone and causes bone growth/spurs à bone fusion over time — Treatment ¡ *Biologics/TNF inhibitors ¡ Analgesics ¡ Exercise ¡ Anti-inflammatories Anklosing Spondylitis — Diagnosis ¡ X-ray of lower spine ¡ Sacroiliac joint is often first affected in AS patients *(+)HLA-B27 ÷ 90+% of patients with AS are HLA-B27 positive — Ocular manifestations ¡ ÷ ¡ ¡ ¡ ¡ ¡ Complete blood count (CBC) C-reactive protein (CRP) Erythrocyte sedimentation rate (ESR) (-) Antinuclear antibody (ANA) (-) Rheumatoid factor (RF) *Anterior uveitis affects about 20-40% of patients Usually episodic, unilateral, acute anterior uveitis ÷ Bilateral at some time for 80% of cases ÷ ¡ Consider AS if patient has an acute, recurrent, unilateral anterior uveitis 4. Psoriatic Arthropathy — See lecture 29 – Dermatologic Diseases — MOA: same as psoriasis except in joints ¡ ¡ 15% of patients will develop arthritis 20-40% are HLA-B27 positive — Acute or chronic anterior uveitis may occur in conjunction with psoriatic arthritis ¡ ¡ Not associated with psoriasis without arthritis. 20% of patients will have iritis — Diagnosis is based on: ¡ ¡ ¡ Typical dermatological lesions Arthritis of fingers Nail changes Bottom Line: Inflamm. Arthropathies — Ocular Manifestations: ¡ ***Uveitis/Iritis*** ¡ *Epi/Scleritis* Quick Summary Slide Spondylarthropathy (+)HLA-B27 Iritis Development Total Combined ~70% 20-40% Crohn’s Disease 50-60% 2.5% Ulcerative Colitis 50-60% 5-10% Reactive Arthritis 60-90% 3-12% *Ankylosing Spondylitis 90-95% 20-40% Psoriatic Arthritis 20-40% 20% Bottom Line: In patients who have iritis and are HLA-B27 positive, there is an underlying spondylarthropathy in 84% of cases! Look further after HLA-B27 testing! Rosenbaum JT. Rheum Dis Clin North Am. 1992;18:143-51. Questions??? — Tower 932 — [email protected]