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Rheumatology Review. SLE. Multisystem inflammatory autoimmune disorder: Antibody and immune complex deposition Females >> Males , African-American , young to middle age Symptoms/Signs Constitutional: H/A, fatigue, fever, weight loss, arthralgias MS: arthralgias, myalgia, arthritis

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Rheumatology Review


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slide2
SLE
  • Multisystem inflammatory autoimmune disorder: Antibody and immune complex deposition
  • Females >> Males, African-American, young to middle age
  • Symptoms/Signs
    • Constitutional: H/A, fatigue, fever, weight loss, arthralgias
    • MS: arthralgias, myalgia, arthritis
    • Derm/mucosal: patchy alopecia, malar rash, discoid lesions, livedo reticularis, vasculitic purpura, Raynaud phenomenon, photosensitivity, soft palate/oral ulcers
    • Renal: Glomerulonephritis, nephrotic/nephritic syndromes, ARF/CRF
    • Psychiatric/Neuro: H/A, depression, seizures, psychosis, TIA/CVA, peripheral and cranial neuropathy
    • Cardiac: pericarditis/pericardial effusion, Serositis, Libman-Sacks endocarditis  Mitral Regurgitation, CAD/infarction, coronary thrombosis
    • Pulmonary: pleural effusion, Serositis, pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, infarction
    • GI: autoimmune hepatitis (jaundice), mesenteric vasculitis  bowel infarction, hepatosplenomegaly
slide3
SLE
  • Hematologic: anemia (Fe-deficient vs Anemia of chronic disease vs. Autoimmune hemolytic), pancytopenia (esp. lymphopenia), hypocomplementemia
  • Ocular: Keratoconjunctivitis Sicca, retinal hemorrhages, cotton wool spots, uveitis
  • Other: Antiphospholipid antibodies
    • Lupus Anticoagulant: prolongation of aPTT (clotting and recurrent miscarriage)
    • Anticardiolipin (ACL) antibodies
  • Antiphospholipid antibody syndrome
    • Recurrent vessel occlusion (Hypercoagulable state), fetal loss, thrombocytopenia, livedo recticularis + Antiphospholipid antibodies, but without features of SLE
diagnostic criteria american rheumatology association
Diagnostic Criteria: American Rheumatology Association
  • Any 4 of the Following:
    • Malar Rash
    • Discoid rash
    • Photosensitivity
    • Oral Ulcers
    • Arthritis involving more than 2 joints (Polyarthritis)
    • Serositis (Pleuritis, Pericarditis, Peritonitis)
    • Antinuclear Antibody titer positive
    • Renal disease (proteinuria)
    • Neurologic disorder (Seizures, Psychosis)
    • Anemia, Neutropenia or Thrombocytopenia
    • Anti-dsDNA, Anti-Sm positive, Syphilis False Positive
diagnosis sle antibodies
Diagnosis: SLE Antibodies
  • Antinuclear (ANA): highly sensitive only
  • Smith Antibody (Anti-Smith or Anti-Sm)
    • Low sensitivity, high specificity
  • Double Stranded DNA Antibody (Anti-dsDNA)
    • Low sensitivity, high specificity
    • Correlates with disease activity and lupus nephritis
  • Histone Antibody (Anti-histone)
    • Associated with drug induced lupus (Procainamide, Isoniazid, Hydralazine)
sle other antibodies other diagnostics
SLE: Other + Antibodies, Other Diagnostics
  • Anti-ribosomal P (sPecific, Psychosis)
  • Anti-Ro (Anti-SSA)
  • Anti-La (Anti-SSB)
  • Anti-RNP
  • Coombs test–positive
  • Inflammatory markers: ESR, CRP
sle treatment
SLE: Treatment
  • Supportive/emotional support
  • Rest, NSAIDS: arthralgias
  • Corticosteroids: visceral complications
  • AntiMALARials: rash, arthralgias
  • Anticoagulation: Antiphospholipid antibody syndrome
  • Immunosuppressants: recalcitrant to steroids
slide8
RA
  • A chronic systemic inflammatory disease with synovial membrane affliction. Characterized by inflammation of ligaments and proliferation/thickening of synovium, leading to destruction of various tissues such as cartilage, bone, tendons, the joint capsule, ligaments, and blood vessels. The key component of immune complex formation occurs due to crosslinkage of rheumatoid factor (IgM) against IgG.
  • Joint changes: chronic synovitis with pannus formation  erosion of cartilage, ligaments, tendons, bone
slide9
RA
  • Females > males, Middle aged
  • Symptoms/Signs
    • MS: symmetric joint manifestations
      • Swelling, warmth, tenderness, pain, morning stiffness > 1 hour (↓ during day)
      • PIP, MCP joints, wrists; elbows, knees, ankles, MTP
        • Spares: DIPs, T-spine, LS-spine
      • Mononeuropathies: median nerve entrapment
      • Cervical spine: atlantoaxial subluxation
ra extra articular signs
RA: Extra-Articular Signs
  • SQ Rheumatoid nodules
    • Of bony prominences, bursae, tendon sheaths
  • Constitutional: malaise, weight loss, low-grade fever, anorexia
  • Vasculitis: palmar erythema, digital hemorrhagic infarction, palpable purpura
  • Anemia of Chronic Disease (normochromic/cytic)
  • Cardiac: pericarditis/pericardial effusion, block
  • Pulmonary: effusion, pleuritis, interstitial fibrosis, nodules (Caplan syndrome), and bronchiolitis obliterans-organizing pneumonia (BOOP)
  • Ocular: Keratoconjunctivitis Sicca, Scleritis, Episcleritis, Keratitis, Scleromalacia
ra diagnosis
RA: Diagnosis
  • Rheumatoid Factor
    • Sensitive, not specific
    • Present in 75% of those with disease
    • Correlates with disease severity and prognosis
  • + ANA
  • Elevations in IgG and IgM
  • Normochromic/cytic anemia
  • Leukocytosis or leukopenia
  • ESR, CRP ↑
  • Radiological changes (X-Ray)
    • Early: soft tissue swelling, juxta-articular demineralization
    • Late: uniform joint space narrowing, bony erosions, subluxation
ra treatment
RA: Treatment
  • Supportive
  • Rest, emotional support
  • Physical therapy
  • Joint rest
  • NSAIDS
  • DMARDS: methotrexate, antimalarials, steroids, sulfasalazine, leflunomide, azathioprine, cyclosporin A, minocycline, gold salts, penicillamine
  • TNF blockers: etanercept, infliximab, and adalimumab
  • Interleukin receptor blockers: anakinra
juvenile ra still s disease
Juvenile RA (Still’s Disease)
  • Chronic synovial inflammation in children < 16 yrs old for at least 6 weeks; symmetric joint disease
  • 3 Subtypes
    • Pauciarticular (Most common, females > males, age < 8)
      • Affects 4 or fewer joints, associated w/ Uveitis
    • Polyarticular: bimodal age distribution (1-6 or 11-16 years), > 5 joints
    • Systemic: hepatomegaly and splenomegaly, lymphadenopathy, high daily relapsing/spiking fever, recurrent evanescent “salmon-pink” rash; pericarditis, heart failure
jra diagnostics
JRA: Diagnostics
  • ESR
  • ANA
  • RF
  • Radiological
  • Echo
jra treatment
JRA: Treatment
  • NSAIDS
  • Methotrexate
  • Ophthalmology consult
  • Physical therapy, splinting, orthotics
rheumatic fever
Rheumatic Fever
  • Develops in children and adolescents following pharyngitis with group A beta-hemolytic Streptococcus (Streptococcus pyogenes)
  • Diagnosis: Jones Criteria
    • Two Major Criteria or,
    • One Major and 2 Minor Criteria + Documented GABHS
      • Major
        • Carditis (ie, endocarditis  mitral stenosis, pericarditis)
        • Polyarthritis (transient, migratory)
        • Sydenham's Chorea
        • Erythema marginatum
        • Subcutaneous Nodules
rheumatic fever1
Rheumatic Fever
  • Minor Criteria
    • Arthralgias
    • Fever
    • Elevated Sedimentation Rate (ESR)
    • Elevated C-Reactive Protein
    • Prolonged PR interval on Electrocardiogram
  • Documented GABHS infection
    • Throat culture, Rapid Strep antigen test, antistreptolysin O (ASO)
rheumatic fever2
Rheumatic Fever

Treatment and Prevention:

  • Appropriate antibiotics

Complications

  • Mitral insufficiency and stenosis
  • Endocarditis
  • Heart failure
  • Dysrrhythmia
systemic sclerosis
Systemic Sclerosis
  • Chronic condition of skin and internal organ fibrosis; results from inflammation and progressive tissue fibrosis and occlusion of the microvasculature by excessive production and deposition of types I and III collagens
  • 2 Subtypes
    • Limited (80%)
      • CREST syndrome, limited to face and hands
      • Calcinosis, Raynaud phenomenon, esophageal hypomotility (GERD  Barrett esophagitis), Sclerodactyly, Telangiectases
    • Diffuse
      • Sclerosis of trunk and proximal extremities
systemic sclerosis1
Systemic Sclerosis
  • Musculoskeletal
    • arthralgia, myalgia, ↓range of motion, symptoms of carpal tunnel syndrome, muscle weakness
  • Respiratory
    • dyspnea, chest pain, pulmonary artery hypertension, dry persistent cough due to restrictive lung disease
  • Cardiovascular
    • pericardial effusion/pericarditis, CHF, myocardial fibrosis, RVF
  • Renal system
    • Hypertension, renal crisis, CRI
  • Vascular system
    • Raynaud phenomenon, fingertip ulcers, cutaneous & mucosal telangiectasis
  • Skin
    • Pruritus, tightness and induration, hyper/hypopigmentation
systemic sclerosis2
Systemic Sclerosis
  • GI
    • GER caused by lower esophageal sphincter (LES) incompetence and decreased or absent peristalsis in the lower 2/3 of the esophagus hoarseness, aspiration pneumonia, and dysphagia. Also dyspepsia, bloating, early satiety, alternating constipation/diarrhea  malabsorption, impaired sphincter function
  • ENT
    • Sicca syndrome
  • Constitutional
    • Fever, malaise, weight loss
  • Neurological
  • - H/A, CVA
systemic sclerosis3
Systemic Sclerosis
  • Raynaud phenomenon
    • pallor, cyanosis, and/or rubor on the hands bilaterally in response to cold or emotional stress
    • Treatment
      • Mainstay: Calcium channel blockers
      • Others: topical nitroglycerin
systemic sclerosis diagnostics
Systemic Sclerosis: Diagnostics
  • Antinuclear antibodies
  • Topoisomerase I antibodies (Scl-70)
  • Anticentromere antibodies
  • Radiological
  • CBC and BMP
  • UA
  • PFT
systemic sclerosis treatment
Systemic Sclerosis: Treatment
  • GERD: H2 blockers, PPIs
  • GI hypomotility: prokinetic agents (cisapride)
  • Renal crisis prevention: ACE inhibitors
  • Pulmonary interstitial fibrosis: cyclophosphamide
  • GI malabsorption: tetracycline
fibromyalgia
Fibromyalgia
  • A common (3-5% prevalence), painful, female predominant rheumatic syndrome, without definite causation. Links to depression, viral infection, and abnormal sensory perception exist
  • Pain Pattern: bilateral, chronic, aching pain and tenderness, with stiffness, that is periarticluar, above and below the waist, > 3 months.
    • Concentration of pain and stiffness around the neck, shoulders, lower back, and hips
fibromyalgia1
Fibromyalgia
  • Other Hx: sleep disruption, fatigue, depression, anxiety, mood changes, diminished concentration, digital numbness/tingling, altered temperature sensation, headaches, constipation/diarrhea, urinary frequency
  • Fever, weight loss, and weakness are not findings
  • Physical: Unremarkable except for multiple tender points in specific locations, > 11 tender points per patient
fibromyalgia diagnostics
Fibromyalgia: Diagnostics
  • Negative work up
  • R/o serious illnesses: a diagnosis of exclusion

DDX

  • Chronic Fatigue Syndrome: Common in females/adolescents, characterized by persistent or relapsingfatigue/lassitude (not MS pain) over > 6 months. Must also have 4 of the following:
    • Constitutional: Sore Throat, low grade fever
    • Painful cervical or axillary lymph nodes
    • Forgetfulness or memory impairment
    • Myalgias or muscle discomfortMigratory, non-inflammatory arthralgia
    • New, Generalized Headaches
    • Sleep disturbance (not refreshing)
    • Generalized Fatigue after Exercise over 24 hours
fibromyalgia treatment
Fibromyalgia: Treatment
  • Antidepressants
    • TCAs and SSRIs
  • Muscle relaxants
    • Flexeril
  • Exercise program
  • Physical therapy
  • Stress management, support groups
  • NSAIDS, opiates, and steroids are ineffective!
  • “It’s not in your head”
vasculitis syndromes
Vasculitis Syndromes
  • A group of disorders characterized by inflammation and necrosis of blood vessels. The purported cause is an autoimmune reponse to: infection,and reactions to drugs and vaccines
  • Are classified based on vessel size affliction and/or body system predilection
  • Symptoms arise from direct damage to the blood vessels or from indirect damage to tissues (such as nerves or organs) whose blood supply has been disrupted.
small vessel vasculitis
Small Vessel Vasculitis
  • Microscopic polyarteritis, microscopic polyangiitis (MPA)
  • Manifestations:
    • Palpable purpura
    • Hematuria (glomerulonephritis)
    • Hemoptysis
    • Arthralgias and Myalgias
    • Neuropathy: mononeuritis multiplex
    • Constitutional
polymyalgia rheumatica
Polymyalgia Rheumatica
  • Pain and stiffness in the shoulder and pelvic girdles + constitutional. Also: neck, arm, thigh pain; associated w/ temporal arteritis.
  • No weakness!
  • Labs:  ESR, normocytic/chromic anemia
polymyositis dermatomyositis
Polymyositis/Dermatomyositis
  • Idiopathic inflammatory myopathy
  • Characterized by progressive proximal lower and upper extremity muscular weakness
  • Addition of: dusky red malar rash, heliotrope periorbital edematous rash, “shawl sign,” or dorsal PIP/MCP scaly patches (Gottron’s sign) = dermatomyositis
  • Labs:  creatine kinase, aldolase, ANA
gouty arthritis
Gouty Arthritis
  • Arthritis resulting from the deposition of sodium urate crystals in one or more joints. Due to: overproduction of uric acid and/or the underexcretion of uric acid
  • Presentation: sudden onset of intense monoarticular joint pain (m/c 1st MTP – podagra). Joints are tender, swollen, warm, with overlying erythema.
    • Fever, and tophi (w/ chronic dz)
gout diagnosis
Gout: Diagnosis
  •  uric acid, ESR, WBC
  • X-Ray
  • Joint fluid aspirate
    • Needle-like sodium urate crystals, negatively birefringent
gout treatment
Gout: Treatment
  • Acute Attack
    • Indomethacin
    • Colchicine
    • COX-2 inhibitor
    • Corticosteroids
  • Maintenance
    • Overproducer: allopurinol
    • Under-excreter: probenecid
pseudogout
Pseudogout
  • Deposition of Calcium Pyrophosphate Dihydrate Crystals; associated with chondrocalcinosis of affected joints
  • Knee is the most commonly affected joint
  • Joint aspirate
    • CPPD crystals, rhomboid-shaped, positively birefringent
  • Tx
    • Underlying chondrocalcinosis
    • NSAIDS, joint aspiration, steriods, COX-2 Inhibitors
septic arthritis
Septic Arthritis
  • Must always consider in DDX of gout/pseudogout
  • Nongonococcal (M/C: S. aureus) vs. N. gonorrhoeae
  • Sudden, acute pain, swelling, hot joint.

+ fever/chills

    • Usually knee; also hip, wrist, shoulder, ankle, elbow
  • Labs: Synovial fluid aspirate
    • Turbid: Non-GC Bacteria; clear to opaque: GC, TB
    • Gram stain & culture
    • Synovial fluid WBCs > 50,000 cells/µL (  PMNs)
  • Blood cultures
seronegative spondyloarthropathy
Seronegative Spondyloarthropathy
  • Absence of serum autoantibodies (i.e., RF)
  • HLA-B27 association
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Inflammatory Bowel Disease with Spondyloarthropathy
  • Reactive Arthritis (e.g. Reiter's Syndrome)
ankylosing spondylitis
Ankylosing Spondylitis
  • Inflammatory axial joint disease; “Sacroiliitis”
  • Affects young males
  • Characterized by chronic lower back pain + radiation to thighs/gluteus, ascending, with stiffness and  ROM. Also: peripheral oligoarticular arthritis
  • Other:
    • Anterior Uveitis
    • Microscopic Colitis
    • Restricted lung disease (fibrosis), AV block, AI
  • DX
    • X-ray: Bamboo spine, erosions, sclerosis
    •  ESR, + HLA-B27
reiter s syndrome
Reiter’s Syndrome
  • “Reactive arthritis”: follows dysenteric infection (shigella, salmonella, yersinia, campylobacter), STD (chlamydia, ureaplasma), or HIV
  • Aseptic oligoarticular arthritis is asymmetric and affects knees & ankles. Also: sacroiliitis or ankylosing spondylitis
  • + constitutional: fever, weight loss
  • Dermatological/mucosal
    • Oral ulcers and stomatitis, keratoderma blennorrhagica, circinate balanitis
reiter s syndrome1
Reiter’s Syndrome
  • Clinical tetrad: urethritis, conjunctivitis (or uveitis), mucocutaneous lesions, and aseptic arthritis
  • Labs:
    • normocytic normochromic anemia
    • ↑ ESR, + HLA-B27
  • Tx:
    • NSAIDS
    • Tetracyclines
    • Sulfasalazine