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120 Cards in this Set
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1. Symmetric Proximal Muscle Weakness
2. Elevated Muscle Enzymes (CPK, Aldolase, Transaminases, LDH) 3. Myopathic EMG Abnormalities 4. Typical changes on Muscle Biopsy 5. Typical Rash of Dermatomyosits |
Proposed Diagnostic Criteria for Polymyositis & Dermatomyositis*
PM: 4/5 criteria DM: rash + 3/4 criteria |
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1. Palpable Purpura
2. Age <20 Years at Disease Onset 3. Bowel Angina (Abdominal Pain After Meals or Bowel Ischemia Usually with Bloody Diarrhea) 4. Granulocytes in Walls of Arterioles or Venules on Biopsy * Must have 2 of 4 criteria. |
Henoch-Schonlein Purpura*
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Malar Rash
Discoid Rash Photosensitivity Oral Ulcers Arthritis Serositis Renal Disorder Neurologic Disorder Hematologic Disorder Immunologic Disorder Antinuclear Antibody |
SLE
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1. Spiking Fever for at Least 5 Days
2. Bilateral Conjunctival Congestion 3. Oropharyngeal Involvement: Diffuse Oropharyngeal Erythema, Strawberry Tongue, or Redness, Dryness and Fissures of the Lips 4. Polymorphous Erythematous Rash 5. Cervical Lymphadenopathy 6. One or More of the Following Signs: Indurative Edema of Hands and Feet, Erythema of Palms and Soles,Desquamation of Fingers and Toes About 2 Weeks After Onset Transverse Grooves in Nails 2 to 3 Months After Onset * Must have 5 of 6 criteria. |
Kawasaki Disease: Diagnostic Guidelines*
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Age > 50 Years at Disease Onset
New Headache Temporal Artery Abnormality (Tender or Decreased Pulse) Elevated Westergren ESR > 50 mm/Hr (high SED rate = high inflammation) Abnormal Artery Biopsy with Mononuclear Cell Infiltrate, Granulomatous Inflammation, Usually with Multinucleated Giant Cells) *Must Have 3/5 Criteria need biopsy for dx |
Giant Cell (Temporal) arteritis
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pain over proximal muscles
muscle weakness |
PMR: pain over proximal muscles
Polymyocitis: muscle weakness |
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Systemic Features:
Polymyalgia rheumatica Fever Anorexia Malaise Weight loss Elevated ESR Abnormal liver function Anemia Local Manifestations Temporal Headache Blindness Scalp Necrosis Jaw claudication Cranial and Peripheral neuropathies Neuropathies Rare organ involvement |
Giant Cell (Temporal) arteritis
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Weight Loss > 4 kg
Livedo Reticularis Testicular Pain or Tenderness Myalgias, Weakness, or Leg Tenderness Mononeuropathy or Polyneuropathy Diastolic BP > 90 mmHg Elevated BUN or Creatinine Hepatitis B Virus Arteriographic Abnormality Biopsy of Small or Medium Artery Containing PAN *Must have 3/10 Criteria |
PAN
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Asthma
Eosinophilia > 10% WBC Mononeuropathy or Polyneuropathy Transitory Pulmonary Infiltrates Paranasal Sinus Abnormality Biopsy with Extravascular Eosinophils *Must have 4/6 Criteria. (ANCA positive) |
Churg-Strauss Syndrome (Allergic Granulomatosis and Angiitis)
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Nasal or Oral Inflammation (Oral Ulcers or Bloody Nasal Drainage)
Abnormal Chest Radiograph (Nodules, Fixed Infiltrates, Cavities) Urinary Sediment (> 5 RBC/hpf or RBC Casts) Granulomatous Inflammation on Biopsy (In Wall of Artery or Arteriole, Perivascular, or Extravasular) *Must have 2/4 Criteria. (ANCA positive, pulm and renal dz, abn CXR, casts) saddle nose |
Wegener's Granulomatosis
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Microscopic Polyangiitis
Wegener’s granulomatosis Churg-Strauss syndrome |
ANCA – associated vasulitis (small-medium vessel)
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ANCA-positive (%) 80-90
Typical results* c-ANCA/proteinase 3 Upper respiratory tract Nasal septal perforation Saddle-nose deformity Subglottic stenosis Lung Nodules, infiltrates or cavitary lesions Kidney NCGN, occasional granulomatous features Distinguishing features Destructive upper airway disease, granulomatous inflammation |
Wegener's granulomatosis
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nasal polyps, allergic rhinitis, asthma, infiltrates, abundant eosinophils
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Churg Strauss
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Age > 16 Years at Disease Onset
Medication at Disease Onset Palpable Purpura Maculopapular Rash Biopsy Including Arteriole and Venule with Granulocytes in Perivascular or Extravascular Location *Must have 3/5 Criteria. |
Hypersensitivity Vasculitis*
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Patients Affected
At Least 50 Years Old Usually Caucasian Muscle Pain Persisting for at Least 1 Month Shoulders Pelvic Girdle Severe Morning Stiffness and Gelling No Muscle Atrophy or True Weakness Erythrocyte Sedimentation Rate > 40 mm/Hr In Many Patients > 100 mm/Hr Rapid Relief with Small Doses of Glucocorticoids (small dose >> rapid relief) |
Polymyalgia Rheumatica
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Prevalence and Epidemiology:
16 million are affected in the U.S. Incidence increases with age. Men equal to women. Clinical Profile Age > 40 or history of trauma Pain presents as initial symptom Shorter period of stiffness (15 minutes or less) Crepitus: crackling of the joints. Most commonly affected joints: Weight Bearing Joints PIP and DIP joints of the hand Asymmetrical joint involvement Swelling caused by synovitis or synovial fluid. Deformity can result from excessive osteophyte development around the joint Bouchard’s Node Herberden’s Node |
OA
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Produces physiologically important prostaglandins
Constitutively expressed Gastric mucosa; small and large bowel mucosa Kidney Platelets Vascular endothelium |
COX 1
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Produces prostaglandins that mediate inflammation and pain
Induced mainly at inflammation sites Induced by cytokines |
COX 2
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Celebrex (celecoxib)
Vioxx (rofecoxib) |
COX 2 inhibitors
Valdecoxib (Bextra) is 2nd generation cox 2 inhibitor |
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OA:
Dose* Up to 4 grams daily Hepatic toxicity associated with alcohol use Possible interaction with anticoagulants |
acetaminophen
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used for OA, neuralgia, trigeminal
Mechanism of Action Two complementary mechanisms of action: 1) Weak µ-opioid receptor agonism, but is too weak by itself to account for the total effect 2) Weak inhibition of norepinephrine and serotonin reuptake, but also too weak by itself to account for the total effect |
Ultram (Tramadol HCI)
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OA
A recent advance for the treatment of pain when physical therapy, exercise, and simple analgesics are not enough. a natural substance that helps cushion and lubricate joints such as the knee Avoids naproxen-like gastrointestinal side effects Patients can get many months of relief with just one course of treatment May cause pain, swelling, heat and/or redness at injection site - generally mild and temporary Mechanisms of action Viscosupplementation (leading effect, makes synovial fluid more viscous) Anti-inflammatory action Removal of oxygen free radicals Supressive effect on matrix metalloproteinases Structural disease-modifying effect ? |
Hyaluronate
Synvisc |
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Arthritis or Arthralgia 55%
Skin Involvement 20% Nephritis 5% Fever 5% Other 15% Organ Involvement Joints 90% Skin Rashes 70% Discoid Lesions 30% Alopecia 40% Pleuropericardium 60% Kidney 50% Raynaud’s 20% Mucous Membranes 15% CNS (Psychosis/Convulsions) 15% |
SLE
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Malar Rash Fixed Erythema, Flat or Raised, Sparing Nasolabial Folds
Discoid Rash Raised Patches, Adherent Keratotic Scaling, Follicular Plugging; Older Lesions May Cause Scarring Photosensitivity Skin Rash from Sunlight (the only subjective criteria)*** Oral or Nasopharyngeal Ulcers Usually painless** Arthritis Nonerosive, Inflammatory in Two or More Peripheral Joints Serositis Immunologic Disorder Antinuclear Antibody Test Pleuritis or Pericarditis (any serousal cavity) Antibodies to ds-DNA or Smith or False Positive Serologic Test for syphilis Positive |
SLE
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Renal Disorder Persistent proteinuria or cellular casts
Neurologic Disorder Seizures or Psychosis Hematologic Disorder Hemolytic Anemia, Leukopenia (<4,000 / mm3) Lymphopenia (<1,500 / mm3) Thrombocytopenia (<100,00 / mm3) |
SLE
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Livedo reticularis
Jacud's arthropathy |
SLE
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drug induced:
atenolol, captopril, statins |
SLE
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Venous Thrombosis
Arterial Thrombosis Recurrent Fetal Loss Thrombocytopenia Livedo Reticularis (associated w/ phospholipid antibodies) |
anti-phospholipid syndrome of SLE
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No past pregnancy morbidity (no tx or 81mg ASA)
One early first-trimester loss (low dose 81mg ASA) Multiple early losses or one late fetal loss (prophylactic heparin + 81mg ASA) Past venous or arterial thrombosis (therapeutic anticoag w/heparin w/ or w/out 81mg ASA) |
MANAGEMENT OF ANTIPHOSPHOLIPID ANTIBODIES IN PREGNANCY
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Visits every 1-3 months with vital signs, physical examination and laboratory tests
Aggressive proactive management of blood pressure, blood sugars, serum lipids, weight Yearly bone densitometry Annual electrocardiogram and chest X-rays Dietary counseling Prompt evaluation of all fevers Periodic treadmill or stress testing Screening for and prophylactic management of antiphospholipid Annual EKG: higher incidence of CAD*** |
SUPPORTIVE MEASURES FOR SEVERE LUPUS
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two most common anti-phospholipid antibody test used in SLE:
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IgG and IgM (anti-cardiopin antibodies)
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An Uncommon Idiopathic Disease
Peak Onset 20 - 50 Female: Male 3:1 Predisposing Factors Include: Genetic HLA - A1, B8, DR3, DR5 Environmental: Chemical Agents eg., Vinyl Chloride, Grape Seed Oil Drugs eg., Pentazocine, Bleomycin |
scleroderma
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AI and vascular dz features
Excessive synthesis of collagen by fibroblasts and increased production of matrix proteins. Endothelial cell injury with increased vascular permeability. Progressive vascular narrowing. Antibodies to the kinetochore portion of the centromere can be identified in most patients with limited cutaneous scleroderma. Antibodies to topoisomerase (SCL-70) develop in 25% of patients with diffuse scleroderma |
scleroderma
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Reversible Skin Color Change
White to Blue and Red Due to Vasospasm Induced by Cold or Emotion ________ in Musculoskeletal Disorders Scleroderma 90% Overlap or Mixed (undifferentiated) 85% SLE 25% DM or PM 20% RA 10% |
Raynaud's phenomenon
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calcinosis (can rupture) Also: renal failure and HTN
raynaud's esophageal dysmotility sclerodactylee telangictasias |
CREST (a form of systemic sclerosis ie scleroderma)
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benign form of scleroderma
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morphia
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puffy edema and induration of arms and legs, sparing hands and feet.
tx: steroids |
eosinophilic fasciitis
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excessive ingestion of L-Tryptophan; involves muscle and fascia with elevations of serum aldolase and severe myalgias; may see peripheral neuropathy, systemic vasculitis, pulmonary infiltrates, Guillain-Barré and rashes.
tx: get rid of supplement causing problem |
eosinophilic-myalgia syndrome
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Symmetrical Progressive Proximal Weakness
Muscle Biopsy Showing Inflammatory Changes Elevated Muscle Enzymes (eg. CPK) Electromyographic Abnormalities (eg. Polyphasic Potentials) Characteristic Dermatological Changes Also: aldolese |
Diagnostic Criteria of Dermatomyositis and Polymyositis
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two common drugs associated w/myopathy
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corticosteroids and statin drugs
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Clinical Features
(can overlap w/ RA and others) Sicca Complex Dry Eyes, Dry Mouth Rheumatoid Arthritis or Other CTD Salivary Gland Enlargement Purpura Nonthrombocytopenic, Hyperglobulinemic Vasculitic Renal Tubular Acidosis or Other Tubular Disorder Polymyopathy, Trigeminal Neuralgia Central Nervous system Disease Chronic Liver Disease Chronic Pulmonary Disease Lymphoma (40x higher risk of lymphomas) Immunoglobulin Disorder Cryoglobulinemia, Macroglobulinemia |
SJOGREN'S SYNDROME
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Diagnostic tests
Schirmer’s Test Rose Bengal Staining Slit Lamp Examination Parotid Salivary Flow Rate Measurement Scintigraphy Sialography Minor Salivary Gland Biopsy |
SJOGREN'S SYNDROME
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1. Serologic
Positive anti-RNP at a hemagglutination titer of 1:1600 or higher 2. Clinical Edema of the hands Synovitis Myositis Raynaud’s phenomenon Acrosclerosis Requirements for the diagnosis: Serologic criteria plus at least three clinical. (When edema, Raynaud’s phenomenon and acrosclerosis are combined, four clinical criteria are required.) |
CRITERIA FOR THE DIAGNOSIS OF MCTD
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Nonmodifiable:
Personal history of fracture as an adult History of fracture in first-degree relative Caucasian race Advanced age Female sex Dementia Poor health/fragility Potentially modifiable Oral steroid therapy for >3 months Current cigarette smoking Alcohol (>2 drinks per day) Low body weight (<127 lbs) Estrogen deficiency (<45 years) Low calcium intake (lifelong) Impaired vision Recurrent falls Inadequate physical activity Poor health/frailty |
osteoporosis
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VERTEBRAL FRACTURES AND LIFETIME RISK OF SUBSEQUENT FRACTURES
1 vertebral fracture at baseline > 2 or more vertebral fractures at baseline > 1 symptomatic vertebral fracture at baseline > |
1 vertebral fracture at baseline > 5 fold ↑ in vertebral fracture
2 or more vertebral fractures at baseline > 12 fold ↑ in vertebral fracture 1 symptomatic vertebral fracture at baseline > 2 fold ↑ in hip fracture |
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Normal
Osteopenia Osteoporosis Severe Osteoporosis |
Normal < 1 SD below the mean
Osteopenia < 1 SD to 2.5 SD Osteoporosis > 2.5 SD Severe Osteoporosis > 2.5 SD with fragility fractures |
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Z-Score
Males younger than age 50 Females prior to menopause Use Z score for analysis: Z score What is considered abnormally low for age? |
Z score 2.0 or below is considered abnormally low for age
Z score above 2.0 is now considered within normal limits for age |
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Bone Mass and Fracture Risk
Spine ↓ 1 SD Hip ↓ 1 SD |
Bone Mass Fracture Risk
Spine ↓ 1 SD ↑ 1.9 times Hip ↓ 1 SD ↑ 2.4 times |
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Osteoporosis: seen in malignant bone marrow ca, renal failure, lytic bone dz, anemai, Waldenstrom's macroglobinemia, MM
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Urine Bence-Jones protein
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bone formation and resorption markers. All formation are based on? and resorption are based on?
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Formation
Serum osteocalcin Serum bone alkaline phosphatase Serum procollagen I extension peptides Resorption Urinary N-telopeptide collagen crosslinks Urinary deoxypyridinoline Urinary hydroxyproline |
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Direct product of bone resorption
Found in urine as stable end-product of degradation Identify rapid bone density loss Monitor therapy Measure dose response Compliance |
Collagen Cross-Linked N-Telopeptides (NTx)
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Premenopausal Women aged 25 to 50
Pregnant and Nursing Women Postmenopausal women < 65 on ERT Postmenopausal women not on ERT All women over age 65 |
Premenopausal Women aged 25 to 50 1000mg
Pregnant and Nursing Women 1200 - 1500mg Postmenopausal women < 65 on ERT 1000mg Postmenopausal women not on ERT 1500mg All women over age 65 1500mg |
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Prevents Bone Loss (but not very good at osteoporosis prevention)
Bone and Cholesterol-Lowering Benefits Effect on Breast Incidence of breast pain and tenderness comparable to placebo Effect on breast cancer, no clinical trials; effects beyond 30 months unknown Effect on Endometrium No association with endometrial proliferation Effect on endometrial cancer; no increase in clinical trials; effect beyond 30 months unknown Increase incidence of endometrial disorders as compared to placebo |
Raloxifene (Evista)
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parathyroid hormone used for osteoporosis
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Forteo
Other uses for Forteo: PTH Treatment Multiple fractures Fracture on Antiresorptive Treatment Males Corticosteroid Induced Pre-treatment with Alendronate may impair bone density response seen with PTH |
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Qualified Beneficiaries
Estrogen-deficient women at clinical risk for osteoporosis Individuals with vertebral abnormalities Individuals receiving chronic glucocorticoid therapy Individuals with primary hyperparathyroidism Individuals being monitored to assess the response to or efficacy of any FDA approved osteoporosis drug therapy Frequency of testing every two years |
Bone Mass Measurement Act
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All women > 65 years of age (regardless of risk factors)
All postmenopausal women < 65 years of age who have at least one additional risk factor for osteoporosis (besides menopause) All postmenopausal women who present with fractures All women who are considering therapy for osteoporosis and whom BMD test results would influence decision All women who have been receiving hormone replacement therapy for a prolonged period. Recommended Treatment for: All women with a T-score > 2.0 All women with a T-score > 1.5 with one or more additional risk factors High-risk women (age >70 years with multiple risk factors) without BMD testing. |
National Osteoporosis Foundation Guidelines
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In this test, the patient lies supine; the affected leg is flexed, abducted, and externally rotated. Lower the leg toward the table. A positive test elicits anterior or posterior pain and indicates hip or sacroiliac joint involvement.
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Faber maneuver
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History of joint complaints lasting > six weeks.
Symptoms localized in joint 3 cardinal signs: limited ROM, pain, swelling |
arthritis
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Pain
Swelling Warmth Erythema Synovial Thickening (spongy feel) |
Is It Inflammatory Arthritis?
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Morning stiffness Focal, brief
Constitutional symptoms Absent Peak period of discomfort after prolonged use Locking or instability implies loose body, internal derangement, or weakness Symmetry (bilateral)Occasional Tenderness Unusual Inflammation (fluid, ten- derness, warmth, erythema, synovitis) Unusual Multisystem disease No Lab abnormalties No |
Noninflammatory disorders (e.g., OA)
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Morning stiffness significant, prolonged, > 1 hr
Constitutional symptoms Present Peak period of discomfort After prolonged inactivity Locking or instability Uncommon Symmetry (bilateral) Common Signs Tenderness Over entire exposed joint area Inflammation (fluid, ten- derness, warmth, erythema, synovitis) Common Multisystem disease Often Lab abnormalties Often |
Inflammatory disorders (e.g., RA, lupus)
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infectious arthritis: common, crystal induced arthritis: common, OA: common usually lower extremities, trauma: common, AVN: uncommon, tumors: uncommon, systemic dz: uncommon
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monoarthritis
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the CBC will often Show:
Normocytic, Normochromic Anemia Thrombocytosis (high platelet count |
RA
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Rheumatoid Factor Not Diagnostic Because:
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Positive 5% General Population
May or May Not be Positive in RA May be Negative Early, Positive Later Positive in Other Diseases CRP is more specific |
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acute phase reactant:
dz activity radiologic progression elevated in RA may be elevated in non-ra |
C reactive protein
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Non-acute phase reactant:
usually elevated in RA (>20mm/hr sig) increases w/age women higher than men |
ESR
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Present in 20 - 40% of Rheumatoid Arthritis Patients
Usually Present with SLE and Scleroderma Patients If negative: excludes active SLE |
antinuclear antibodies (ANA)
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d/o of coagulation: causes clots
Venous Thrombosis Arterial Thrombosis Recurrent Fetal Loss Thrombocytopenia Livedo Reticularis (cardio lipo antibodies??) |
Anti-Phospholipid Syndrome
APS |
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vascular d/o, usually affects women, lower extremeties, aggrevated by cold, associated w/anti-cardiolipin antibodies and anti-phospholipid syndrome (APS)
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livedo reticularis
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Antibodies to Neutrophils (ANCA)
Peri-nuclear (P-ANCA) - 80% seen in _____ Cytoplasmic (C-ANCA) - seen in Wegener’s, Other Systemic Vasculitides or Crescentic Glomerulonephritis |
Antibodies to Neutrophils (ANCA)
Peri-nuclear (P-ANCA) - 80% seen in Wegener’s granulomatosis Cytoplasmic (C-ANCA) - seen in Wegener’s, Other Systemic Vasculitides or Crescentic Glomerulonephritis |
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Causes:
Joint Sepsis Crystal Synovitis Rheumatoid Arthritis and Other Inflammatory Diseases |
pyarthrosis
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Some Causes:
Trauma Bleeding Disorders Villonodular Synovitis Pyrophosphate Arthropathy Charcot Joint (=neuroarthropathy) Resolving Infection Contamination During Aspiration |
hemarthrosis
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synovial:
clear, colorless viscous leucocytes <200, (<25% PMNs) |
normal
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synovial
clear, yellow viscous leukocytes 200-2,000 (<25% PMNs) |
noninflammatory
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synovial
cloud, yellow, watery, glucose may be low leukocytes: 2,000 - 100,000 (>50% PMNs) |
inflammatory
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synovial
purulent, glucose very low leukocytes: >80,000 (>75% PMNs) |
septic
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arthritis evaluation
hand in supinated oblique position |
Norgard
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Any age up to 45 - 65
Women: Men 3:1 Genetic predisposition likely Clinical Profile: Age can be younger than in Initial symptoms may resemble the flu Joint pain with swelling, heat, redness Pannus formation Excerbations and remissions common Symmetrical joint involvement General malaise Stiffness is prolonged |
RA
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what are the two central mediators in RA, involved in both inflammation and jt destructive processes
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interleukin 1
TNF alpha |
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in RA, these are considereed what?
TNF, IL-1, IL-6, IL-7, chemokines |
proinflammatory
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Four or more of the following criteria must be present:
Morning stiffness > 1 hour Arthritis of > 3 joint areas Arthritis of hand joints (MCPs, PIPs, wrists) Symmetric swelling (arthritis) Serum factor nodules Radiographic changes First four criteria must be present for 6 weeks or more. |
RA
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diagnostic for RA
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anti-CCP ab or RF positive
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what imaging tests are best for RA?
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MRI and ultrasound
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Complete ability to perform usual daily activities (eg self-care, vocational / avocational)
Ability to perform usual self-care and vocational activities; limited avocational activities. Ability to perform usual self-care activities; limited vocational / avocational activities Limited ability to perform usual self-care / vocational / avocational activities |
Criteria for Assessing Functional Status in Rheumatoid Arthritis
Class I Complete ability to perform usual daily activities (eg self-care, vocational / avocational) Class II Ability to perform usual self-care and vocational activities; limited avocational activities. Class III Ability to perform usual self-care activities; limited vocational / avocational activities Class IV Limited ability to perform usual self-care / vocational / avocational activities |
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clinical evaluation should include:
extra-articular features measure of inflammatory activity measure of destruction and deformity |
RA
Articular: measures of inflammatory activity Check for tenderness, stress pain, synovial effusion, grip strength and duration of morning stiffness Articular: measures of destruction and deformity Check for lax collaterals, subluxation, malalignment, metatarsal prolapse, hammer toes and bone-on-bone crepitus |
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A minimum of five of the following for at least 2 consecutive months:
1. Morning stiffness not to exceed 15 minutes 2. No fatigue 3. No joint pain 4. No joint tenderness or pain on motion 5. No soft tissue swelling in joints or tendon sheaths 6. ESR (Westergren’s method) less than 30mm/h (females) or 20mm/h (males) Exclusions prohibiting a designation of complete clinical remission: Clinical manifestations of active vasculitis, Pericarditis, Pleuitis, Myositis, And/or unexplained recent weight loss or fever secondary to RA |
CRITERIA FOR CLINICAL REMISSION OF RHEUMATOID ARTHRITIS
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A diagnosis requires the presence of all of the following:
Fever >39°C Arthralgia or arthritis Rheumatoid factor <1:80 Anti-nuclear antibody <1:100 In addition to any of the two following: White blood cell count > 15,000 cells/mm³ rash Pleuritis or pericarditis Hepatomegaly or splenomegaly or generalized lymphadenopathy (Also: ferritin levels) |
Adult Still's Dz
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Carries the Risk of:
Retinal Toxicity with Vision Loss Reversible Corneal Deposits Without Vision Loss Used Most Commonly In: Early Disease Mild to Moderate Disease Complete Eye Exam* Needed: Prior to Initiation of Therapy At Six-Month Intervals Thereafter *Including white and red dot visual field test. Retinal Toxicity Risk May be Reduced if Daily Dosage Does Not Exceed 200 mg. Other adverse reactions: Nausea, Cramping, Bloating Hyperpigmentations, Rash |
Hydroxychloroquine (Plaquenil)
for RA |
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Pros
Clinical Effectiveness Demonstrated in Short-term Use Mild Level of Toxicity Cons Effective for Mild-to-Moderate RA Contraindicated in Patients with Sulfa Intolerance or G6PD Deficiency Toxicities: Myelosuppression, Gastrointestinal, CNS Rate of AEs Dose-Dependent CBC Every 2 - 4 Weeks for 3 Months, then Every 12 Weeks |
Sulfasalazine
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Pros
Effective in Refractory RA Cons High Risk for Severe Leukopenia and/or Thrombocytopenia Other Toxicities: Hepatotoxicity, May Increase Cancer Risk, High Risk for Opportunistic Infections, Macrocytic Anemia, Severe Bone Marrow Depression Required Monitoring Every 1 - 2 Weeks with Dosage Change, Every 1 - 3 Months Thereafter |
Azathioprine
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SE:
Skin and mucous membranes Rash, mouth ulceration, pemphigus Gastrointestinal tract Loss of taste (early phase of therapy), nausea and vomiting Blood Thrombocytopenia and neutropenia, occasional marrow aplasia Renal Proteinuria and hematuria, glomerulonephritis, occasional nephrotic syndrome Muscle Myasthenia gravis and myositis Auto-immune Drug-induced SLE Lung Bronchiolitis obliterans (rare) |
D-penicillamine for RA
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most commonly prescribed DMARD, used in 60% of U.S. patients.
Mechanism of action unknown in RA, but may inhibit an enzyme in the folic acid pathway. More rapid onset of action than most traditional DMARDs within 3 to 6 weeks Initial dose 7.5 mg/wk; may be increase up to 25 mg/wk to improve response Potential for liver, hematologic and pulmonary toxicity Regular liver enzyme monitoring recommended every 4 to 8 weeks Contraindicated in women who are or may become pregnant due to teratogenic potential Gastrointestinal events may be seen in up to 60% of patients Folic acid recommended at 1 mg/day to improve tolerability |
methotrexate
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Pyrimidine Synthesis Inhibitor
Selective for Dihydroorotate Dehydrogenase Metabolized in Liver to Active Metabolite Well Absorbed Orally Required Loading Dose Prolonged Half-life (14 days) Teratogenic There is an antidote |
Leflunomide (Araba) for RA
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Adverse Reactions
Hypertension Acne Hirsutism, hyperadrenalism, Moon Facies, Growth Retardation (children), Irregular Menses Osteoporosis, Aseptic Necrosis Risk of Infection Gastric Ulcer Cataracts Psychosis |
Systemic Corticosteroids
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has been identified as a key role player in the pathogenesis of chronic inflammatory diseases, including AS, and appears to have a central role in the pathogenesis of joint destruction as illustrated.
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TNF
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Effects of ?
Stimulates release of prostaglandins and chemokines Induces tumor lysis (mouse fibrosarcoma) Mediates shock (endothelium) Stimulates T-cell proliferation Causes apoptosis Activates neutrophils Suppresses lipoprotein lipase |
TNF
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adverse effects
Serious infections and sepsis Mainly in patients with underlying illness or receiving immunosuppressive therapy CNS demyelinating disorders Use with caution or avoid use in patients with transverse myelitis, optic neuritis, multiple sclerosis Pancytopenia Causal relationship unclear Use with caution in patients with history of hematologic abnormalities Autoantibody formation Discontinue if lupus-like symptoms are observed Heart failure Carefully monitor if prescribed to patients with heart failure |
Etanercept (Enebrel)
anti-TNF for RA |
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anti-TNF drug for RA that is not yet approved for tx of RA in US
SE: include HF |
Inflixamab
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Contraindications:
Current or recurrent infections Tuberculosis Multiple sclerosis Lupus Malignancy Pregnant or lactating |
Contraindications for Anti-TNF Therapy
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Fusion protein
-First in the new class of "costimulation blockers" for treatment of RA -Prevents T-cell activation via binding CD80 and CD86 on antigen-presenting cells |
Abatacept
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safety issues associated w/?
Maligancy Lymphoma Lung Cancer Melanoma and nonmelanoma skin cancers History of malignancy Safety in pregnancy Cardiovascular effects Heart Failure Reduced cardiovascular risk of myocardial infarction and stroke |
Safety issues with biological response modifiers
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IL-1 blocking drug for RA
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Anakinra (Kineret)
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only sythetic collagen available for OA of the knee
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Synvisc
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Early disease
Rapid escalation of methotrexate dose + low-dose corticosteroid Aggressive step-up combination (add hydroxychloroquine and/or sulfasalazine) Switch to targeted cytokine inhibition + methotrexate |
CURRENT RECOMMENDATIONS FOR THE TREATMENT OF RA SYNOVITIS
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Etanercept (Enbrel)
Inflixamab (Remicade) (the most indications) Adalimumab (Humira) |
TNF blockers
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Pathogenesis
Direct Extension Bacteremia from Distant Infection Pathophysiology Cytokine Release Proteolytic Enzymes Formation of Antigen-antibody Complex Inhibition of Proteoglycan Synthesis Activation of Coagulation System |
INFECTIOUS ARTHRITIS
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Clinical Presentation
Usually Monoarticular, Most Commonly Knee Co-morbid Factors Childhood and Elderly Rheumatoid Arthritis Prosthetic Joint Drug Abusers Organism Most Commonly: Gram Positive Staph aureus Most Common anaerobe: B Fragilis Gonococoal |
INFECTIOUS ARTHRITIS
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associated with what dz?
diffuse gonoccocal infection Dactylitis of the ring finger as a result of tenosynovitis in a 24-year-old woman Disseminated gonococcal infection skin lesion. Hemorrhagic vesicle over a distal interphalangeal joint. Looks like area of necrosis |
infectious arthritis
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1. Erythema infectiosum in children (slap cheeck)
2. Adults may have self-limited rheumatoid-like arthritis with intermittent flares (can do lab test for virus) |
viral arthritis
Parvovirus B19 |
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1. Association with Reiter’s syndrome, Sjogren’s syndrome, psoriatic arthritis and pondyloarthropathy.
2. Described with low titer ANA, phospholipid antibodies 3. Wide spectrum of clinical manifestations; large joints more commonly involved. 4. Polyarteritis nodosa-like syndrome with vasculitis of medium- sized vessels and mononeuritis. 5. May see x-ray findings of inflammatory arthritis and/or spondyloarthropathy. 6. Carefully monitor immunosuppressive therapy? |
infectious arthritis: viral arthritis: HIV
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Original Geographic Clustering
Now Recognized as Chronic Multisystem Disease Caused by Spirochete (Borellia borgdorfii); Transmitted by Tick Known Geographic Distribution Today |
lyme dz
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Stage I - Early
Pathoneumonic: Erythema Chronica Migrans (central clearing: disappears when treated) (goes away even if not treated but can have complications) Flu-like Syndrome, Malaise, Fever, Myalgia, Arthralgia, Headache, Stiff Neck Stage II - Early Disseminated Multiple or Recurrent Erythema Migrans, Borrelia Lymphocytoma, Migratory Arthralgia/Arthritis, Meningoencephalitis, Peripheral Neuropathy (Bell’s Palsy), Carditis (Conduction Defects) Stage III - Late , Acrodermatitis Chronic Atrophicans, Intermittent/Chronic Oligoarthritis, Chronic Meningoencephalitis or Encephalitis, Sensorimotor Neuropathies |
lyme dz
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Early Migratory Arthralgia 20%
Midcourse Intermittent Oligoarthritis 60% Late Chronic Oligoarthritis 10% |
lyme dz
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Diagnosis:
Best made in Setting of Typical Signs and Symptoms, and Exposure History in Endemic Area Isolation of B. Burgdorferi Low Yield Procedure Indirect Immunofluorescence (IFA) and Elisa Assays may Confirm False Positives with IFA and Elisa (best by hx and physical vs blood test) |
lyme dz
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Early infection (local or disseminated)
Adults Doxycycline, 100 mg orally twice daily for 14-21 days Amoxicillin, 500 mg orally three times daily for 14-21 days or (alternatives in case of doxycycline or amoxicillin allergy) Cefuroxime axetil, 500 mg orally twice daily for 14-21 days Erythromycin, 250 mg orally 4 times a day for 14-21 days Children (ages 8 years or less) Amoxicillin, 250 mg orally 3 times a day for 50 mg/kg per day in 3 divided doses for 14-21 days or (alternatives in case of penicillin allergy) Erythromycin, 250 mg orally 3 times a day or 30 mg/kg per day in 3 divided doses for 14-21 days |
lyme dz
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Musculoskeletal Syndromes Associated with:
Arthralgia Infectious Arthritis Opportunistic Infections Pyogenic Infection Reiter’s Syndrome Psoriatic Arthritis Myositis Sjogren’s Syndrome Undifferentiated Spondyloarthropathy AIDS - Associated Arthritis Painful Articular Syndrome Avascular Necrosis of Bone |
HIV infection
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Inflammatory Bowel Disease
Sarcoidosis Fungal Infections (coccydiomycosis) Drug Reactions Streptococcal Pharyngitis Psittacosis Tuberculosis Yersiniosis Leptospirosis LGV |
ERYTHEMA NODOSUM:
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A. Occurs in southwestern U.S. Can present as erythema nodosum, arthritis and/or bilateral hilar adenopathy.
B. Most common joints: knees, wrists, hands, ankles, elbows and feet. C. Treatment – Amphotericin B, ketoconazole or fluconazole. Surgical treatment if unresponsive to medical management |
COCCIDIOIDOMYCOSIS
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A. Systemic granulomatous disease of unknown etiology. May mimic other rheumatic diseases.
B. Granulomas found in lung (86%), lymph nodes (86%), spleen (63%), heart (20%), kidney (19%), bone marrow (17%) and pancreas (6%). C.Clinical features. 1. 8 times higher incidence in blacks. 2. 90% have abnormal chest x-ray. 3. Constitutional signs and symptoms D.Rheumatologic manifestations 1. Arthritis in 10-15% 2. Arthritis as initial manifestations; additive; periarticular swelling; episodes of weeks to months 3. Chronic arthritis; 6 months or more after diagnosis; dactylitis, x-ray changes with destructive and/or cystic changes 4. Other manifestations.E. Extrathoracic 1. Peripheral lymphadenopathy. 2. Hepatomegaly/abnormal liver enzymes 3. neuro 4. Cardiopulmonary 5. Renal-membranous GN, calcinosis, renal insufficiency. 6. Leukopenia, hypercalcemia*, elevated ACE*. (not specific) |
SARCOIDOSIS
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postage stamp
hypercalcemia elevated ACE |
SARCOIDOSIS
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