Arthritis Flashcards
Oligoarthritis vs. Polyarthritis
Oligo - under 5 joints
Poly - 5+ joints
Typical Characteristics of RA
- symmetrical
- deformation (subluxation), damage, and erosion of joints
- worse in the morning with prolonged stiffness (30m+)
- involves any synovial joint (even neck) EXCEPT NOT DIPs
- soft tissue swelling, ulnar deviation of fingers, swan neck, boutonniere, poor grip strength
- more common (and often more severe) in indigenous
Typical Characteristics of Lupus (SLE)
- symmetrical polyarthritis
- Worse in the AM, prolonged morning stiffness (30m+)
- does NOT involve the DIPs
- does NOT result in erosions or sclerosis
- Skin rash (butterfly rash), photosensitivity, alopecia, mouth ulcers, Raynaud’s, Sjorgen’s
- 90% are female, genetic component
Typical Characteristics of Psoriatic Arthritis
- what are two subtypes of PsA?
- asymmetric
- oligoarthritis
- worse in the AM, prolonged morning stiffness (30m+)
- commonly involves the DIPs
- both erosion and sclerosis present
- psoriasis common on scalp, ears, extensor surfaces of elbows/knees, gluteal surface, onycholysis, nail pitting
- sausage digits, dactylitis
- more often skin precedes the joints
- often assx with metabolic syndrome, CV, depression, pancreatic cancer, lymphoma
- equally common in men and women
- Psoriatic Spondylitis - ank spond in the presence of psoriasis
- Arthritis Mutilans - rare, melting of joints
Sero (+) vs. (-) RA
- either RA factor and/or CCP (+) or (-)
- Sero (+) has a worse prognosis/ joint disease/ increased chance of extra-articular features
- smokers are likely to have both CCP and RA (+)
Time Course of RA
- Only 50% of patients are sero (+) in the beginning, but 85% of patients will be sero (+) after 1 year
What is RA factor?
- IgM Ab against the Fc component of IgG (pentavalent and can form large complexes)
- Non-specific and can be (+) in other conditions (i.e. 35% of lupus will be RA positive)
What is anti-Cyclic Citrullinated Peptide (anti-CCP or ACPA) ?
- auto Abs that target peptides with cirtulline
- often present early/ before RA factor
- (+) in 60% of patients (not as sensitive) but highly specific
Pathophysiology of RA
- what is a pannus?
- synovitis, synovial hypertrophy with pannus formation
- pannus is many cell layers thick, neovascularization, macrophages and lymphocytes (invasive tumor in situ that erodes bone)
- RA is a disease of subtraction (does not have sclerosis and osteophytes like OA does)
- genetic (HLADR1), exogenous triggers such as virus, bacteria (p.gingivalis), smoking induced CCPs, molecular mimicry
- macrophage presents Ag to TCR which requires co-stimulatory molecules (abatacept can block)
- activated T cells release cytokines (TNFa, IL-6)
- T cells tell B cells and plasma cells to make auto Abs (RA factor, which forms ICs and activates complement and chemotaxis by PMNs)
- Adhesion molecules important for aggression and adhering of cells
- Innate immunity also activated (TLRs and NB)
- Osteoclasts activated which results in erosion of bone and cartilage, osteopenia of subchondral bone
Pharmacologic Treatment of RA
- Different classes of drugs used
- Mild vs active?
- most important drugs early on are DMARDs
- if mild –> plaquenil (hydroxychloroquine - will need eye exams), sometimes SZS and MTX
- if very active –> combo of plaquenil, MTX, and SZS (and treat right away!!!)
*DMARDs and biologics only drugs that prevent progression and damage
- cortisone injections/ prednisone only used as a bridge while starting DMARDs (can cause osteoporosis and avascular necrosis)
- NSAIDs often used
- Biologics –> i.e. TNFa inhibitors (adalinumab), B lymphocyte inhibitors (Rituximab), co-stimulatory molecule inhibitors (abatacept), IL-6 inhibitor (toclizumab)
- EXPENSIVE and not first line, have to fail DMARDs first
*non-pharm: exercise, diet (high protein), lower BMI, NO SMOKING, omega 3s
Extra-Articular Features of RA
- What is Sjorgen’s?
- Sjorgen’s - keratoconjunctivitis sicca (dry eyes), dry mouth, parotid gland enlargement, cavities
- rheumatoid nodules in lungs, heart, LNs, spleen, bone, skin, nerves
- atlanto-axial subluxation (can lead to quadriplegia)
What should you always do before ordering ANA?
- do a rheumatological ROS otherwise your ordering a sensitive but very non-specific test
- ANA can be positive in both RA and lupus (but much more commonly + for lupus)
- Do not order just for back pain or fatigue/rash/ hair loss
Examples of Sero (-) arthritis
- Psoriatic arthritis (which i’m thinking is actually a subtype of…)
- Ankylosing Spondylitis (and its 4 subtypes)
What should mono arthritis make you suspicious of?
- infection
- tap joint for synovial fluid
Synovial Fluid Analysis
- characteristics of OA/RA and infection/ Gout, lupus, and PsA
- numbering system
OA –> thick/viscous, clear, low WBC, mainly mononuclear cells
RA/infection –> watery, turbid, high WBC, mainly polynuclear cells
Gout/Lupus/PsA –> Similar to RA (gout specifically will have negatively birefringent crystals, yellow parallel and blue perpendicular)
0 - Normal, very low WBCs and mononuclear
1 - OA, viscous, clear, low WBCs (monos)
2 - Inflammatory, thin, watery, opaque, high WBCs (polys)
3 - Septic, (+) culture, very high WBCs (polys)
4 - Hemorrhagic, RBCs, no clotting
Typical Characteristics of Ankylosing Spondylitis (Spondyloarthritis)
- Symmetric
- Worse in the AM, prolonged morning stiffness (30m+)
- Erosion, but no sclerosis
- usually chronic LBP/ buttock pain in young patients (20-40), more common in men/ Haida natives
- HLAB27 Genotype in 80%
- lower limb oligoarthritis, sacroilitis
- affects the axial spine with lesions often at the enthuses where ligaments and tendons insert, may be syndesmophytes (bone bridging)
- can lead to MI/stroke/spine fractures
4 Types of Ankylosing Spondylitis (Spondyloarthropathies)
- Idiopathic (primary)
- Reactive arthritis (Reiter’s) - Triad of conjunctivitis, urethritis or dysentery, arthritis
- Psoriatic Spondylitis
- Spondylitis of IBD
*always ask about psoriasis, conjunctivitis, iritis, sx of IBD, sexual hx, diarrhea, dysentery, travel, etc.
*screen if one of these (including HLAB27 (+) and sx under 40/45 that have lasted at least 3 months)
What are features of inflammatory back pain? What should this make you suspicious of? Treatment?
- 4 of: insidious onset, onset under 40 years lasting over 3 months, worse/nil with inactivity, better with exercise, pain at night that improves with getting up
- prolonged AM stiffness, alternate butt pain, improved with NSAIDs
- should be concerning for Spondyloarthropathies
- postural exercises are best, also NSAIDs and TNF inhibitors
- anti-TNF for axial
- SSZ/MTX for peripheral
Common lab tests in rheumatology and when to order
- Which unique tests are only done once vs. retested?
- CBC
- ESR, CRP (overly sensitive and non-specific)
- Cr and urinalysis (follow especially if SLE/vasculitis)
- CK as baseline in setting of muscle weakness/ statins
- RA factor and CCP if likely inflammatory arthritis
- ANA if likely lupus (very sensitive, poor PPV)
- 1/640 is higher titre than 1/80
DON’T CHANGE OVER TIME
- if ANA is positive and suspicious –> ENA
- ENA is either SSA (Ro) or SSB (La) which can occur in lupus or Sjorgen’s
- this Ab crosses the placenta –> risk for congenital heart block (all fertile pts with lupus should do ENA)
FOLLOW
- if ANA is positive can also do DNA Ab (more specific, but only + in 50% of cases)
- can also order C3/4, which often decrease in lupus
Treatment of Lupus
- plaquenil (hydroxychloroquine) for everyone –> helps skin/joints/hair/organs
- prednisone, AZA, MTX, cyclosporine, tacrolimus, NSAIDs, cyclophosphamide (can cause early gonadal failure), biologics
- SPF 50+, no smoking, immunization, bone protection, treat comorbidities
Artherosclerosis and Arthritis
- both RA and lupus can increase mortality from atherosclerotic and endothelial cell damage in coronary vessels
- risk increases with use of prednisone
Gout
- dx
- assx features
- increased risk
- tx
- monosodium urate/ uric acid crystals
- dx by microscope (yellow parallel, negatively birefringent crystals, blue perpendicular)
- acute pain, red hot joint
- often part of metabolic syndrome (BMI, DM, HTN, dyslipidemia), renal insufficiency
- increased risk with diuretics (HCTZ) and low dose ASA as they interfere with uric acid excretion, also meat and beer
- do NOT treat if asymptomatic hyperuricemia
- NSAID (indocid) or Colchicine or Prednisone/Corticosteroid IV
- do NOT start allopurinol right away as this will prolong acute attack via mobilization gout
- only treat if 3+ attacks, and use colchicine/NSAID until uric acid is normal
Temporal/ Giant Cell Arteritis
- tx
- CANNOT miss this –> blindness
- new onset of headaches over 50, jaw claudication pain, scalp tenderness
- assx with polymyalgia rheumatica
- Tx - high dose prednisone, test ESR/CRP, temporal artery biopsy (but always treat first!!!)
Typical characteristics of OA
- can be symmetric or asymmetric
- no prolonged morning stiffness
- worse in the PM
- can involve DIPs
- no erosion but yes sclerosis
Signs of RA on Xray?
- generalized, concentric, uniform joint space loss
- valgus deformity
Diagnosis of Spondyloarthritis?
- XR (sometimes CT, MRI) of SI joints
- sacroilitis on imaging AND at least 1 SpA feature OR
- HLAB27 and at least 2 other SpA features
*may take years for changes to develop, some may never develop
*classification gold standard is a rheumatologists opinion - clinical sx –> STRONG - IBD, psoriasis, uveitis, peripheral arthritis
- SPARCC Enthesitis Index –> look at 16 sites, score 0-16
Treatment of Spondyloarthropathies?
- exercise and physiological (especially core strengthening), weight loss, education
- NSAIDs, biologics (TNFis, IL-17Ais, JAKis), potentially surgery
- NO: steroids, DMARDs
Psoriatic Arthritis Criteria
3 or more of:
- psoriasis (current or personal/family hx)
- nail signs
- (-) for RA factor
- dactylitis (current or personal/family hx)
- Xray evidence of new articular bone
Treatment of Psoriatic Arthritis
- non-pharm
- pharm - mild vs severe
- exercise, assistive devices, relaxing, fatigue management, diet/weight, rarely surgery
- mild –> NSAIDs, steroid injections (DMARDs if more than 3 months)
- mod/severe –> DMARD (except plaquenil (and oral steroids) not recommended), biologics (must try 2 DMARDs)
*goal is to have max of one tender/swollen joint
Pathophysiology of Lupus
- autoimmune, auto Ab production against cell nuclei (may be stimulated by UV light)
- formation of immune complexes, defective phagocytosis, increase innate and adaptive imunity
Lupus Criteria
At least 4 of (must be 1 clinical, 1 immune) and ANA > 1:80:
- Clinical –> acute or chronic cutaneous, oral/nasal ulcers, pericarditis, non-scarring alopecia, arthritis, serositis, proteinuria, neurologic, hemolytic anemia, leukopenia, thrombocytopenia
- Immune –> ANA, anti-DNA, anti-smith, antiphospholipid Abs, low C3/C4/CH50, direct Coombs test
- is a clinical diagnosis
Signs and Symptoms of Lupus by system
- Mucocutaneous - malar/annular/ discoid rash, nasolabial sparing, photosensitivity, buccal/palate/tongue/nose ulcers, non-scarring alopecia
- MSK - worse in AM, stiffness for more than 30m+, improves with activity and NSAIDs, joint swelling
- Renal - lupus nephritis, biopsy if rising serum Cr, proteinuria over 500mg, active sediment w RBC casts
- CV - peri/endo/myocarditis, vasculitis, thromboembolisms, Raynaud’s (pallor –> cyanosis –> erythroderma)
- Pulmonary - pleuritis, pleural effusions, ILD, pneumonitis, pull HTN, shrinking lung syndrome
- Neuropsych - stroke, seziures, headaches, neuropathy, psychosis, depression, transverse myelitis, mood change
- GI/hepatic - common adverse med reactions
- Hematologic - anemia, leukopenia, thrombocytopenia
- Other
- antiphospholipid Ab syndrome (hypercoaguable state leading to VTE, pregnancy losses, pre-eclampsia, stroke, MI, will have lupus anticoagulant Ab and anticardiolipin Ab)
- shingles, atherosclerosis, avascular necrosis, osteoporosis, cataracts, bladder/cervical cancer, premature gonadal failure
Different derm types of lupus
- subacute cutaneous (80% SSA/SSB +, very photosensitive)
- discoid (red raised with keratitis scaling, follicular plugging, erythema, atrophy, scarring, telangiectasias)
- bullous/ mucosal/ maculopapular/ photosensitive/ etc.
Different classifications of Lupus nephritis
- III - focal –> hema/proteinuria, nephrotic, under 50% glomeruli
- IV - diffuse –> most severe, same as III but over 50% glomeruli, HTN, low complement
- V - membranous –> hema/proteinuria, nephrotic, may present with no other signs
Tests for Lupus
- CBC, Cr, AST/ALT, TSH, CK, Ca/SPEP, CRP, urinalysis, ACR, HEP/HIV
- specific –> ANA, ENA, C3/4 (will be low), dsDNA (will be high), RA factor, anti-CCP, ANCA, anti-phospholipid Abs
Drug Induced Lupus
- equal in men and women
- sx will stop once drug stopped
- fever, rash, arthritis, serositis, my/arthralgias
- rarely: nephritis, CNS, heme
- C3/4 and dsDNA will be normal but may be ANA+ and anti-histone+
- causes: isoniazid, diltiazem, anti-TNF, procainamide, chlorpromazine, hydralazine, minocycline
Neonatal Lupus
- tx
- transplacental passage on anti-SSA/SSB Abs
- congenital heart block (any degree), bradycardia, hydrops
- rash present at or near birth, photosensitivity, scalp and periorbital area, should resolve by 6-8 weeks
- do a fetal echo, treat with dexamethasone
Fibromyalgia
- tx
- achey pain all over, non-articular but at least 11/18 painful/tender joints in all quadrants
- benign, normal labs, no inflammation - believed to be a increase in centralized pain response, soft tissue disorder
- usually sleep and mood disorders, anxiety
- more common in women
- education and reassurance, aerobic exercise, CBT, psychotherapy
- nighttime tricyclics (ami/noritryptiline), NSAIDs, tramadol (?), melatonin, pregabalin/gabapentin, duloxetine
Polymyalgia Rheumatica
- inflammation, muscle pain, stiffness/ aching in shoulder/ pelvic girdle
- 50-55 y, increased ESR/CRP
- responds in 72h to low dose prednisone
- only test for CRP/ESR
*can be assx with giant cell/temporal arteritis
Plaquenil (Hydroxychloroquine)
- an anti-malarial
- often used if mild RA or lupus is suspected
- oral
- S/E - rash, diarrhea, annual eye exam for depositions
Sulfasalazine
- sulfa and ASA together
- oral, daily
- may be used along with MTX and plaquenil
- useful if PsA/SpA/IBD arthritis
- cannot give if sulpha allergy, have to follow blood work
Methotrexate
- often used alone in moderate/ severe RA
- oral/IM/SC once a week
- highly teratogenic (even in males), have to watch liver enzymes, always put patients on folic acid
- cannot take sulfa ABX, limit EtOH, may cause pneumonitis
Leflunomide (Arava)
- S/E
- very teratogenic
- GI upset, diarrhea, need to follow liver enzymes
- in system for 2 years so need cholestyramine washout
Tests before taking biologics, when not to use
- Hep B/C/HIV/TB
- CXR for TB (treat 1st if positive)
- hold before elective surgery and during infections/ bad colds
Articular vs non-articular pain
Articular - throughout ROM, in all planes of movement, swelling in joint
Non-articular - only with certain movement, may be unrelated to joint movement, swelling is not in the joint but may be around
Inflammatory vs non-inflammatory pain
Inflammatory - worse with rest, better with movement, AM stiffness for more than 30 minutes
Non-inflammatory - worse with movement, no pain/ improvement with rest, AM stiffness under 30 minutes
Sensitivity
Specificity
PPV
NPV
Sensitivity - ability to identify those with disease
Specificity - ability to identify those without disease
PPV - proportion of + results that are actually +
- true positives/ everyone with the disease
NPV - proportion of - results that are actually -
- true negatives/ everyone without the disease
*PPV increases with increased prevalence
*PPV = true positives/ all positive results
Auto Ab Testing
- take patients serum and expose to target Ag, variable region will bind to Ag (thus leaving fixed portion exposed)
- 2nd Ab targeted to Fc of Ab with enzyme/fluorescent tag
- most common are ELISA, IIF, MPBI
Inflammatory Markers
- CRP - acute phase reactant, non-specific opsonin for bacteria
- ESR (erythrocyte sedimentation rate) - measures rate of fall of erythrocytes (mm of clear plasma in tube after 1 hour). Moderate increase indicates inflammation/ anemia/ infection/ pregnancy/ aging, high increase indicates severe infection
ANA
- anti-nuclear Ab
- auto Ab that targets nuclear Ags
- test if SLE suspected (very sensitive, poor specificity)
anti-dsDNA Ab
- auto Ab that target dsDNA
- supports SLE, may correlate with disease activity and flares but not diagnostic
ENA
- extractable nuclear Ag Ab
- auto Ab that targets Ags present in nucleus (i.e. smith Ag, SSA/SSB Ag, histone Ag)
- helps classify CT disorders
Confirmatory Tests for SLE
- anti-dsDNA Ab (specific, cannot exclude if -)
- anti-smith Ab (specific, cannot exclude if -)
- SSA (Ro) Ab (neonatal lupus - rash and heart block)
Small Vessel Vasculitis
- disease targeting small vessels, NOT infection
- i.e. granulomatosis with polyangitis (GPA)
- associated with anti-neutrophil cytoplasmic Ab (ANCA) - test if glomerulonephritis, pulmonary hemorrhage, chronic sinusitis
What comprises a motor unit?
Structure of a muscle?
- motor neuron, NMJ, muscle fibers randomly scattered in a limited area of muscle
- all fibers in a single unit are the same type (fast vs slow)
- muscle –> fascicle –> fiber –> myofibril –> thick/thin filaments –> actin/ myosin
What happens at the NMJ?
- Ap arrives at axon terminal –> voltage gated Ca channels open –> Ca binds Ach vesicles and trigger snare protein complex formation and fusion with pre-synaptic membrane –> Ach released into cleft and bind to AchRs on post-synaptic membrane –> influx of Na along t-tubules of muscle fiber –> depolarized muscle cell allows influx of Ca and cross-coupling/ contraction
Type I vs II Muscle Fibers
I –> slow, more mitochondria, endurance, oxidative metabolism
II–> fast, glycolytic pathway, fatigues easily, subtypes (A,B,C)
Myopathic changes on biopsy
- fibre size variation, internalized nuclei, rimmed vacuoles, ring fibres, abnormal staining, round, ragged-red
*want to order from a muscle that is 4/4-
Muscle Power Grading
0 - no contraction
1- flicker of contraction
2 - full ROM no gravity
3 - full ROM against gravity
4- - minimal resistance
4 - some resistance
4+ - definite but slight weakness
5 - normal power
Positive and Negative symptoms suggesting a muscle disorder
Positive - cramps, contractures, hypertrophy, myalgia, myoglobinuria, stiffness
Negative (most common and predominant) - weak, fatigue, exercise intolerance, atrophy
*prominent pain is not common in most muscle disorders
Examples of:
- proximal muscle weakness
- distal symptoms
- craniobulbar symptoms
- brushing teeth/ hair, lifting overhead, getting in our of chair or car
- foot drop, opening jars, zippers
- dysarthria, dysphagia, ptosis, diplopia
Common Patterns of Weakness
Limb-Girdle - most common/treatable and least-specific, shoulders and hips
- inflamm/immune myopathies, dystrophies
- proximal muscle weakness +/- neck flexors and extensors, orthopnea
Distal Arm-Leg - uncommon, must rule out neuropathy
Distal Forearm Proximal Leg - usually asymmetric
- inclusion body myositis, amyloid, few hereditary forms
Dermatomyositis
- immune mediated myopathy
- rash on back of hands and heliotrope rash on face/nail changes
- may also see interstitial lung disease (pulmonary fibrosis)
- CK is often high
NMJ Disorders
- common example and treatment
- often improve with rest
- clinically and electrically testable (NCS/EMG)
- i.e myasthenia gravis - autoimmune, post-synaptic
- fatigue, diplopia, ptosis, fatiguable dysarthria/chewing/swallowing/weakness
- treat with Acetycholinesterase inhibitors (pyridostigmine) and immunosupressants
Pseudogout
- calcium pyrophosphate dihydrate
- chondrocalcinosis on xray, positively birefringent crystals
- can cause severe inflammatory OA in atypical joints
Scleroderma
- fibrosis of skin/lungs/kidney, CREST localized cutaneous variant…
- Calcinosis in skin
- Raynauds
- Esophageal dysfunction (reflux)
- Sclerodactyly (thickening and tightening of fingers)
- Telangiectasis
Statins can cause…
polyarthralgia and myalgia, can increase CK
Uveitis
- sight-threatening intraocular inflammatory disease
- umbrella term for many disease
- can be anterior (painful), intermediate (vitritus), posterior (blind spots), panuveitis, extraocular (pemphigoid, keratitis, etc.)
Examples of life threatening vs non life-threatening eye conditions
- Non- Life threatening - dry eyes, blepharirits, viral conjunctivitis, allergic, subconjunctival hemorrhage
- Life threatening - infection, inflammation (uveitis, vasculitis, scleritis, keratitis), trauma, masquerades (neoplasms, acute angle closure glaucoma)
Relations Between eye disease and rheumatoid arthopathies and tx
Scleritis - RA, SLE, gout, ANCA vasculitis
Retinal vasculitis - SLE, ANCA vasculitis, antiphospholipid
Uveitis - IBD, HLAB27, PsA, Reiter’s
tx - local steroids, NSAIDs, prednisone, immunosuppression
