Rheumatology Flashcards

Question

What are the differences between seropositive vs seronegative rheumatic disease? Demographics, peripheral arthritis, pelvic/axial disease, enthesitis, extra-articular.

Answer 1

progressive deterioration of cartilage and bone due to failed repair of joint damage caused by stresses on the joint

Answer 2

* primary (idiopathic) * most common, unknown etiology * secondary * post-traumatic or mechanical * post-inflammatory (e.g. RA) or post-infectious * heritable skeletal disorders (e.g. scoliosis) * endocrine disorders (e.g. acromegaly, hyperparathyroidism, hypothyroidism) * metabolic disorders (e.g. gout, pseudogout, hemochromatosis, Wilson’s disease, ochronosis) * neuropathic (e.g. Charcot joints) * atypical joint trauma due to peripheral neuropathy (e.g. DM, syphilis) * AVN * other (e.g. congenital malformation)

Answer 3

* deterioration of articular cartilage due to local biomechanical factors, which leads to joint trauma and release of proteolytic and collagenolytic enzymes * OA develops when cartilage catabolism \> synthesis * loss of proteoglycans and water exposes underlying bone * abnormal local bone metabolism further damages joint * altered joint function and damage * synovitis is secondary to cartilage damage; therefore, may see small effusions in OA

Answer 4

* most common arthropathy * increased prevalence with increasing age (35% of 30 yr olds, 85% of 80 yr olds)

Answer 5

* genetic predisposition * advanced age * obesity (for knee OA) * female * trauma

Answer 6

* blood work * normal FBC and ESR, CRP * negative RF and ANA * radiology: 4 hallmark findings * synovial fluid: non-inflammatory

Answer 7

1. Joint space narrowing 2. Subchondral sclerosis 3. Subchondral cysts 4. Osteophytes

Answer 8

* presently no treatment alters the natural history of OA * non-pharmacological therapy * weight loss (minimum 5-10 lb loss) if overweight * physiotherapy: heat/cold, low impact exercise programs * occupational therapy: aids, splints, cane, walker, bracing * pharmacological therapy * oral: acetaminophen/NSAIDs, glucosamine ± chondroitin (nutraceuticals not proven) * joint injections: corticosteroid, hyaluronic acid (questionable benefit) topical: capsaicin, NSAIDs * surgical treatment * joint debridement, osteotomy, total and/or partial joint replacement, fusion

Answer 9

* chronic, symmetric, erosive synovitis of peripheral joints (e.g. wrists, MCPs, MTPs) * characterized by a number of extra-articular features

Answer 10

* autoimmune disorder, unknown etiology * hallmark of RA is hypertrophy of the synovial membrane * activated rheumatoid synovium (pannus) grows into and over the articular surface; inflammatory mediators lead to release of metalloproteinases and collagenases resulting in destruction of articular cartilage and subchondral bone * two theories attempt to explain chronic remissions and exacerbations seen in RA * sequestered Ag * during inflammation, immune complexes (ICs) are deposited at avascular cartilage-bone junction → immune complexes are released as further cartilage breaks down → triggers inflammatory cascade * molecular mimicry * cartilage damage → altered cartilage resembles undefined offending agent → triggers inflammatory cascade

Answer 11

* prevalence 1% of adult population * F:M = 3:1 * age of onset 20-40 yr * genetic predisposition: HLA-DR4/DR1 association (93% of patients have either HLA type)

Answer 12

* variable course of exacerbations and remissions * morning stiffness \>1 h, improves with use, increases with rest * may have joint pain with activity * symmetric joint involvement * joint swelling, tender joints * constitutional symptoms: profound fatigue; rarely myalgia or weight loss * extra-articular features (EAF) * limitation of function and decrease in global functional status * complications of chronic synovitis * signs of mechanical joint damage: loss of motion, instability, deformity, crepitus, joint deformities * swan neck deformity, boutonnière deformity * ulnar deviation of MCP, radial deviation of wrist joint * hammer toe, mallet toe, claw toe * flexion contractures * atlanto-axial and subaxial subluxation * C-spine instability * neurological impingement (long tract signs) * difficult/dangerous intubation: risk of worsening subluxation and damage to spinal cord * limited shoulder mobility, spontaneous tears of the rotator cuff leading to chronic spasm * tenosynovitis → may cause rupture of tendons * carpal tunnel syndrome * ruptured Baker’s cyst (outpouching of synovium behind the knee); presentation similar to acute DVT

Answer 13

* Srögren's Syndrome (common): keratoconjunctivitis, sicca and xerostomia (dry eyes and mouth) * Caplan’s syndrome (rare): multiple pulmonary nodules and pneumoconiosis * Felty’s syndrome (rare): arthritis, splenomegaly, neutropenia

Answer 14

* blood work * RF sensitivity ~80% but non-specific; may not be present at onset of symptoms * anti-CCP: sensitivity ~80% but more specific; may precede onset of symptoms * increased disease activity is associated with decreased Hb (anemia of chronic disease), increased platelets, ESR, CRP, and RF * imaging * x-rays may be entirely normal at onset * first change is periarticular osteopenia, followed by erosions * U/S, MRI may be used to image hands to detect early synovitis and erosions

Answer 15

* young age of onset * high RF titer * elevated ESR * activity of \>20 joints * presence of extra-articular features

Answer 16

* goals of therapy: remission or lowest possible disease activity * control disease activity * relieve pain and stiffness * Maintain function and lifestyle * prevent or control joint damage * key is early diagnosis and early intervention with DMARDs * “window of opportunity” = early treatment within first 3 mo of disease may allow better control/remission

Answer 17

* Education * Behavioural * exercise program (isometrics and active, gentle ROM exercise during flares, aquatic/aerobic/strengthening exercise between flares), assistive devices as needed * job modification may be necessary

Answer 18

* DMARDs and Biologics * DMARDs: standard of care and should be started as soon as possible * treatments guided by disease severity and prognostic features * MTX is the gold standard and is first-line unless contraindicated * delayed onset of action (may take 8-12 wk) * potential toxicities: GI, hematologic, hepatic (liver enzymes), pulmonary, teratogenic * if inadequate response (3-6 mo) → combine or switch * add-ons include: hydroxychloroquine, sulfasalazine, leflunomide * biologics: indicated if inadequate response to DMARDs * can be combined with DMARD therapy * agents include infliximab, etanercept, adalimumab, abatacept, rituximab, tocilizumab * reassess every 3-6 mo and monitor disease severity * Reducing Inflammation and Pain * NSAIDs * individualize according to efficacy and tolerability * contraindicated or cautioned in some patients (e.g. PUD, ischemic cardiac disease, pregnancy); add acetaminophen ± opioid prn for synergistic pain control * corticosteroids * local * IA injections to control symptoms in a specific joint * systemic (prednisone) * low dose (5-10 mg/d) useful for short-term to improve symptoms if NSAIDs ineffective, to bridge gap until DMARD takes effect * for severe RA, low dose prednisone can be added to DMARDs * do baseline DEXA bone density scan and consider bone supportive pharmacologic therapy if using corticosteroids \>3 mo at \>7.5 mg/d * cautions/contraindications: active infection, TB, osteoporosis, HTN, gastric ulcer, DM

Answer 19

* Weight gain * Osteoporosis * AVN * Cataracts, glaucoma * PUD * Susceptibility to infection * Easy bruising * Acne * HTN * Hyperlipidemia * Hypokalemia, hyperglycemia * Mood swings

Answer 20

* indicated for structural joint damage * surgical options include: synovectomy, joint replacement, joint fusion, reconstruction/tendon repair

Answer 21

* **M**alar rash * **D**iscoid rash * **S**erositis * **O**ral ulcers * **A**NA * **P**hotosensitivity * **B**lood * **R**enal * **A**rthritis * **I**mmune * **N**eurologic

Answer 22

* chronic inflammatory multi-system disease of unknown etiology * characterized by production of autoantibodies and diverse clinical manifestations

Answer 23

* production of autoantibodies causing multi-organ inflammation * multi-factorial aetiology * genetics * common association with HLA-B8/DR3; _~10% have positive FHx * oestrogen * pre-pubertal and post-menopausal women have similar incidence to men * men with SLE have higher concentration of oestrogenic metabolites * infection * viral (non-specific stimulant of immune response) * drug-induced * anti-hypertensives (hydralazine), anti-convulsants (phenytoin), anti-arrhythmics (procainamide), isoniazid, biologics, OCPs * anti-histone Ab are commonly seen in drug-induced SLE * symptoms resolve with discontinuation of offending drug

Answer 24

* Viral: * Influenza * HIV * CMV * Hepatitis A/B/C/D/E * Chicken pox * Bacterial: * Pneumonia * Syphilis * TB * Malignancy: * Leukemias/lymphoma * Hodgkins/non-Hodgkins lymphoma * Drugs: * Substance withdrawal * IgA nephropathy * Autoimmune * Reiters syndrome * Temporal arteritis

Answer 25

* prevalence: 0.05% overall * F:M = 10:1 * age of onset in reproductive yr (13-40) * more common and severe in African Americans and Asians * bimodal mortality pattern * early (within 2 yr) * active SLE, active nephritis, infection secondary to steroid use * late (\>10 yr) * inactive SLE, inactive nephritis, atherosclerosis likely due to chronic inflammation

Answer 26

* blood work: **ANA** (sensitivity 98%, but poor specificity → used as a screening test, **ANA** titres are not useful to follow disease course) * **anti-dsDNA** and **anti-Sm** are specific (95-99%) * **anti-dsDNA** titer and **serum complement (C3, C4)** are useful to monitor treatment response in patients who are clinically and serologically concordant * **anti-dsDNA** increases and **C3 and C4** decrease with disease activity * **antiphospholipid Ab (anti-cardiolipin Ab and SLE anticoagulant**), may cause increased risk of clotting and increased aPTT

Answer 27

* Vasospastic disorder characteristically causing discoloration of fingers and toes (white → blue → red) * Classic triggers: cold and emotional stress

Answer 28

* treat early and avoid long-term steroid use, if unavoidable * if high doses of steroids necessary for long-term control, add steroid-sparing agents and taper when possible * treatment is tailored to organ system involved and severity of disease * all medications used to treat SLE require periodic monitoring for potential toxicity

Answer 29

* dermatologic * sunscreen, avoid UV light and estrogens * topical steroids, hydroxychloroquine * musculoskeletal * NSAIDs ± gastroprotective agent for arthritis (also beneficial for pleuritis and pericarditis) * hydroxychloroquine improves long-term control and prevents flares * bisphosphonates, calcium, vitamin D to combat osteoporosis * organ-threatening disease * high-dose oral prednisone or IV methylprednisolone in severe disease * steroid-sparing agents: azathioprine, MTX, mycophenolate * IV cyclophosphamide for serious organ involvement (e.g. cerebritis or SLE nephritis)

Answer 30

* Calcinosis: calcium deposits on skin * Raynaud’s phenomenon * Esophageal dysfunction: acid reflux * Sclerodactyly: tightening of skin on digits * Telangiectasia: superficial dilated blood vessels

Answer 31

* derangement in purine metabolism resulting in hyperuricemia; monosodium urate crystal deposits in tissues (tophi) and synovium (microtophi)

Answer 32

* sources of uric acid: diet and endogenous * synthesis * hypoxanthine → xanthine → uric acid both steps catalyzed by xanthine oxidase

Answer 33

* primary or genetic * mostly due to idiopathic renal underexcretion (90%) * also idiopathic overproduction or abnormal enzyme production/function * secondary * dietary excess (particularly high consumption of beer, seafood, and meat) * underexcretion (\>90%): renal failure, drugs, systemic conditions * overproduction (\<10%): increased nucleic acid turnover states (e.g. malignancy, post-chemotherapy) * sudden changes (increasing or decreasing) in uric acid concentration are more important than absolute values * acute gout can occur with normal serum uric acid * changes in pH, temperature, or initiation of antihyperuricemics may precipitate an acute gouty attack * common precipitants: alcohol, dietary excess, dehydration, drugs (e.g. thiazide and loop diuretics), trauma, illness, surgery, starting xanthine oxidase inhibitor therapy * other associated conditions: HTN, obesity, DM, starvation

Answer 34

* single episode progressing to recurrent episodes of acute inflammatory arthritis * acute gouty arthritis * severe pain, redness, joint swelling, usually involving lower extremities * joint mobility may be limited * attack will subside spontaneously within several days to weeks; may recur * tophi * urate deposits on cartilage, tendons, bursae, soft tissues, and synovial membranes * common sites: first MTP, ear helix, olecranon bursae, tendon insertions (common in Achilles tendon) * kidney * gouty nephropathy * uric acid calculi

Answer 35

* joint aspirate: \>90% of joint aspirates show crystals of monosodium urate (negatively birefringent, needle-shaped) * x-rays may show tophi as soft tissue swelling, punched-out lesions – erosion with “overhanging” edge

Answer 36

* NSAIDs: high dose, then taper as symptoms improve * corticosteroids: IA, oral, or intra-muscular (if renal, cardiovascular, or GI disease and/or if NSAIDs contraindicated or failed) * colchicine within first 12 h but effectiveness limited by narrow therapeutic range * allopurinol can worsen an acute attack (do not start during acute flare)

Answer 37

* conservative * avoid foods with high purine content (e.g. visceral meats, sardines, shellfish, beans, peas) * avoid drugs with hyperuricemic effects (e.g. pyrazinamide, ethambutol, thiazide, alcohol) * medical * antihyperuricemic drugs (allopurinol and febuxostat): decrease uric acid production by inhibiting xanthine oxidase * uricosuric drugs (probenecid, sulfinpyrazone): use if failure on or intolerant to allopurinol; do not use in renal failure * prophylaxis prior to starting antihyperuricemic drugs (colchicine/low-dose NSAID) * in renal disease secondary to hyperuricemia, use low-dose allopurinol and monitor Cr * indications for treatment with antihyperuricemic medications include: * recurrent attacks, tophi, bone erosions, urate kidney stones * perhaps in renal dysfunction with very high urate load (controversial)

Answer 38

* Skin rash - maculopapular * Allopurinol hypersenitivity syndrome: fatal, erythematous desquamating rash, fever, hepatitis, eosinophilia, and worsening renal function.

Answer 39

* multi-system vasculopathy manifested by recurrent thromboembolic events, spontaneous abortions, and thrombocytopenia * often presents with migraine-type headaches * circulating antiphospholipid autoantibodies interfere with coagulation cascade * primary APLA: occurs in the absence of other disease * secondary APLA: occurs in the setting of a connective tissue disease (including SLE), malignancy, drugs (hydralazine, procainamide, phenytoin, interferon, quinidine), and infections (HIV, TB, hepatitis C, infectious mononucleosis) * catastrophic APLA: development within 1 wk of small vessel thrombotic occlusion in ≥3 organ systems with positive antiphospholipid Ab (high mortality)

Answer 40

* Thromboembolic events: Artherial and venous thrombosis are usually mutually exclusive. * Renal vein thrombosis * Glomerular thrombosis * MI * TIAs * Spontaneous abortions * Thrombocytopenia, haemolytic anaemia, neutropenia * Dermatologic * livedo reticularis * Raynaud's phenomenon * pupura * leg ulcers * gangrene * Migrane headaches * Addison's disease * Epilepsy

Answer 41

* thrombosis * lifelong anti-coagulation with warfarin * target INR 2.0-3.0 for first venous event, \>3.0 for recurrent and/or arterial event * recurrent fetal loss * heparin/low molecular weight heparin ± Aspirin® during pregnancy * catastrophic APLA * high-dose steroids, anti-coagulation, cyclophosphamide, plasmapheresis

Answer 42

* systemic inflammatory condition (ANA and RF negative) with fevers and characteristic rash, numerous systemic symptoms, and may have severe arthritis

Answer 43

* idiopathic; infectious triggers likely – various viruses and bacteria have been implicated * stress increases risk

Answer 44

* Fever * Arthralgias/Arthritis * Rash

Answer 45

* classic triad of symptoms * high-spiking fevers (95.7% of patients, typically T = 102.2ºF/39°C, \<4 h duration, quotidian pattern) * characteristic “salmon rash” (~72% of patients, on proximal limbs + trunk) * arthralgia/arthritis (64-100%) * sore throat, myalgias and serositis may also occur * arthritis is symmetric, typically affects large joints, i.e. wrists, knees and ankles, may involve PIP and DIPs, elbow, MTPs * liver abnormalities ± hepatomegaly (50-75% patients) * splenomegaly (44%)

Answer 46

* ANA and RF negative * markedly elevated ESR, CRP, ferritin (typically \>1000 ng/mL, \>2200 pmol/L) total ferritin \>5x ULN = 80% sensitive, 41% specific * anemia, thrombocytosis, leukocytosis may occur * transaminases, LDH may be elevated

Answer 47

* refer to rheumatologist for treatment with biologics (anti-IL1 and anti-IL6 agents) * begin management with low-dose glucocorticoids ± MTX

Answer 48

* Joint space narrowing * periarticular osteoporosis * Erosions * Periarticular soft tissue swellinig * Later joint destruction or subluxation

Answer 49

* Recurrent oral and genital ulcers * Uveitis * Seronegative arthritis * Central nervous system symptoms * Fever * Thrombophlebitis * Erythema nodosum * Abdominal symptoms, and * Vasculitis.