week 7- MSk 2 Flashcards
• SLE:
o chronic inflam dz
o type III hypersensitivity
o potential type II involvement → auto-Abs against nuclear components of own cells
• SLE epidem:
o F > M 15:1 in child-bearing age
o black 3x > white
o Any age, onset usu 16-55
• SLE etio:
o Genetic:1st-deg relatives 8-9x ↑risk; Epigenetic hypomethylation
o Hormones: E2 (OCPs ↑ risk 50%), P, T, DHEA, PRL, modulate incidence and severity
o Environ: trigger or exacerbate: Infx (Mycobacteria, trypanosomiasis, EBV), Silica dust, Vaccines (HBV, HPV), Allergies (meds, abx), UV light, Stress, Surgery, Pg
o Drug rxn (drug-induced lupus): Reversible, usu dt tx long-term illness, mimics systemic lupus, Statins, Hydralazine, Methyldopa, chloropromazine
• SLE ssx:
o Mild moderate fulminant
o Usu Fatigue, fever,↓wt
o Mucocutaneous: > 90%, non-painful oral ulcers, nail fold infarcts, periungular erythema, spinter hemorrages, Raynauds, alopecia, malar “butterfly” rash (30%)
o MSk: often 1st sx, symmetric, non-deforming arthritis of digits, wrists, knees, MTP, hard to distinguish from RA if other sx absent, prolonged AM stiffness (50%), nodules (7%), myalgia
o Renal: most, only 50% clinical, proteinuria, micro hematuria, GN → ESRF, death
o CVS: mc pericarditis chest pain, mimic MI, Libman-Sacks endocarditis (sterile), atherosclerosis → angina, MI
o Resp: > 50%; mc pleurisy, pleural effusion, pneumonitis, interstitial lung dz, pulm HTN, alveolar hemorrhage; Pulm emboli if lupus anti-coag present
o GI: N/V/D, reflux, non-specific abd pn, peptic ulcers, vasculitis→pancreatitis, peritonitis, colitis
o CNS: ↓cognition, organic brain dos, delirium, psychosis, szs, HA, peripheral neuropathies
o Blood and lymphatics: anemia, thrombocytopenia, leukopenia, peripheral LA, SM, a-PL & a-cardiolipin ↑thrombosis
o Ophthalmologic: keratoconjunctivitis sicca common, Cotton wool exudates dt retinal vasculitis, episcleritis, scleritis, anterior uveitis lc
• SLE labs:
o ANA 95-100%, a-dsDNA (60%, active dz), ↓serum C3, C4 (60%, w flare), + RF (20%)
o Leukopenia, lymphopenia, thrombocytopenia. Abn urinary sediment. Proteinuria. ↑PT, Hypoalbuminuria, ↑creatinine , (+) Coombs, Immune complex assay (cryoglobulins, Raji cell test, C1q precipitins).
o Auto-Abs: a-histone (drug induced, other AI), Anti-ENA- Sm, RNP, RNA-protein complexes (↑spec for SLE, MCTD), Anti-SSA(Ro), SSB(La) (Sjogrens)
• SLE imaging:
o MRI/Cerebral angiography in CNS lupus
o CXR for pulm infiltration, pleural effusion
o Echo for pericardial effusion
• SLE dx criteria:
o 4+/11: (nothing is pathognominc)
o 1. Malar rash,
o 2. Discoid lupus
o 3. Potosensitivity (UV)
o 4. Oral or nasopharyngeal ulcers
o 5. Non-erosive arthritis
o 6. Renal do: proteinuria (>3+ dipstick or >0.5 g/d ) or cylindruria (cellular casts)
o 7. Neuro do: Szs or psychosis
o 8. Serositis: pleuritic, pericarditis, peritonitis
o 9. Bood do: Hemolytic or leucopenia (↓4,000/mL), lymphopenia ( ↓1500/ul ), thrombocytopenia (↓100,000/uL) w/o offending drug
o 10. ANA+ (95-100%) w/o drugs
o 11. Immune do: (+) anti-Sm, anti-ds DNA, anti-PL, or false (+) sero test for syphilis
• SLE ddx:
o RA, MCTD, systemic vasculitis, scleroderma
o metastatic malignancy, fever of unknown origin
o inflam myopathies, viral hepatitis, sarcoidosis
o acute drug rxn, drug induced rxns
o psychogenic rheumatism
o many cutaneous rashes
• progressive systemic sclerosis (scleroderma)
o rare, chronic dz w immune activation, vascular damage,↑ECM, ↑collagen
o localized or systemic →limited cutaneous or diffuse
o CREST syndrome
• scleroderma etio:
o Molecular mimicry w/ CMV o Contaminated rapeseed oil o Polyvinyl chloride o Epoxy resins o Aromatic hydrocarbons o Similar to graft vs host dz
• Localized Scleroderma:
o Morphea
o Linear scleroderma (line of thick skin on extremities)
o Scleroderma en coup de sabre (forehead and face)
o No internal or organ involvement
• Systemic Sclerosis- Limited cutaneous:
o Skin thick distal to elbow or knee
o Can have face involvement
o Begins w raynauds w gradual onset heartburn, tender digital pitting scars or ulcers, thick skin over fingers
o Later pulm fibrosis and pulm HTN
• Systemic Diffuse Scleroderma:
o Any skin affected
o Fibrosis of skin, pulmonary parenchymal and GI tract
o Small Vessel Vasculopathy: raynauds, renal crisis, pulm artery HTN
o More rapid, skin changes quickly, raynauds, internal organ involvement in 2 yrs
o Fibrosis of lungs, heart, GI, renal crisis (↓ blood flow dt vasculitis)
• CREST syndrome
o Mild variant of scleroderma o slow onset and progression, skin hardening usu confined to hands and face, internal organ involvement less severe o much better px o Calcinosis o Raynaud's phenomena o Esophageal dysfunction o Sclerodactyly o Telangiectasia
• Scleroderma ssx:
o Onset: Fatigue, Swollen digits, stiff jts, weak, pain, insomnia, skin discoloration
o Skin: induration symmetric, mb only fingers (sclerodactyly), distal arms or all body; as progresses, skin becomes taut, shiny, hyperpigmented, face becomes mask like; telangiectasias on fingers, chest, face, lips, tongue; subQ calcifications usu fingertips
o MSk: jt contractures, tendon friction rubs, myopathy, myositis, cutaneous calcifications, synovitis, neuropathies
o GI: esophageal dysfxn in most. dysphagia, acid reflux (mb severe), bloating, ↓wt, constipation, gastroparesis, SIBO, Barrett’s metaplasia in 1/3m ↑risk adenocarcinoma
o CV: arrhythmia, EKG abn; pericarditis
o Resp: leading cause of death; Dry cough, DOE, pulm HTN
o Kidney: mb malig HTN
• Scleroderma dx criteria:
o *may miss ppl in early dz w CREST
o Major: skin thick just proximal to MCP’s
o Minor: Sclerodactyly, Permanent ischemia of fingertips, Bibasilar pulm fibrosis
• Scleroderma labs:
o ANA: almost all (+)
o ANA w centromere pattern usu have better course, but more pulm fibrosis
o Anti-Scl 70: ↑risk pulm fibrosis
o CMP: renal involvement
• Scleroderma imaging:
o Echo: PAH
o CT: pulm fibrosis
• Polymyositis/Dermatomyositis:
o Idiopathic inflam myopathies
o present clinically similar, but have distinct immunopathogenicities
o PM: direct T cell mediated muscle injury, in fascicle
o DM: immune complex deposition in blood vessels (B cell)
o DM:↑risk malig (adenocarcinomas of lung, cx, ovaries, pancreas, bladder, stomach)
o 1/100,000
o Peak 40, or any age
o F:M 2:1
• PM/DM ssx:
o symmetric proximal mm weakness
o mm pain (50%)
o Fever, ↓wt, Raynaus, nonerosive inflam polyarthritis
o Rare: cardiomyopathy, dysphagia via weak esophagus, interstitial lung dz (mb fatal)
o DM presents w characteristic rashes
o Gottron’s papules, shawl sign, heliotrope peri orbital rash, erythroderma
• PM/DM work-up:
o PE: Gowers Test (+) o CK, LDH aldolase, AST, ALT o Anti-Jo-1, Anti-SRP, Anti-Mi-2 (+ 30%) o Muscle bx o ANA often (+). If anti-SSA, SSB (+) consider overlap d/o o EMG o skin bx (DM) o MRI: to monitor tx
• PM/DM ddx:
o ALS, Myasthenia gravis, inclusion body myositis o muscular dystrophies o Hypothyroid o HIV, acute infx o meds (steroids, statins)
• polymyalgia rheumatic:
o severe aching and stiffness in neck, shoulder & pelvic girdles
o =rheumatic dz, but unk etio
o Severe pain & stiffness in proximal mm w/o permanent weakness or atrophy
o No evidence on bx.
o Mm strength and EMG normal
o >50, ↑incidence w age, 1/200
o F:M 2:1
• PMR ssx:
o mb acute or subacute
o Pain, stiffness symmetric in neck, shoulder, pelvic girdle
o ↓ROM of joints 2nd to pain
o marked morning stiffness, difficult to get out of bed
o Subjective weakness
o Tenosynovitis
o Malaise, fatigue, depression, anorexia, ↓wt, fever
o Palpable, mild, synovitis in knees, wrists, MCP jts
• PMR labs:
o ESR usu 40-100mm/h o CRP >5 mg/L o Normocytic anemia o ↑ plts o Mb ↑transaminases o ANA, RF, CCP (-)
• PMR imaging:
o Plain films normal
o MRI may reveal tenosynovitis, bursitis
• PMR dx criteria:
o >50 at onset
o BL aching morning stiffness (last 30+ mins), at least 1 mo
o stiffness in 2+/3 area: neck or torso, shoulders or proximal arms, hips or proximal thighs
o ESR ≥40 mm/h
• Concomitant of PMR:
o tendency to Temporal Arteritis (Giant Cell Arteritis)
o Chronic vasculitis of large and medium vessels
• Temporal arteritis ssx:
o Localized HA of new onset o General ill feeling o Tender or ↓pulse of affected artery o Jaw or tongue claudication o Sudden, painless blindness
• Temporal arteritis PE:
o Temporal or occipital artery tenderness
o ↓ temporal artery pulsations
o Red, nodular swollen scalp arteries (rare)
o Ill appearing pt
• Temporal arteritis labs:
o ESR > 50 mm/h
o Bx long segment from above ear: necrotizing arteritis w ↑ mononuclear cells
o Or a granulomatous process w multinucleated giant cells
• Polyarteritis nodosa:
o Systemic vasculitis w necrotizing inflam lesions of medium and small muscular arteries
o Usu at vessel bifurcations, → microaneurysm, rupture w hemorrhage, thrombosis, organ ischemia or infarction
o Very rare, 1-5/ million
o M:F 3:1, 45-65
o 1st: Idiopathic
o 2nd: HBV/HCV infx, hairy cell leukemia
• PAN ssx:
o Affects any organ
o Skin: tender erythematous nodules, purpura, livedo reticularis, ulcers, bullous or vesicular eruption
o Renal: HTN
o Neuro: very common. motor and sensory deficits
o GI: Early Abd pain, worse after eating (angina of gut), N/V, melena, bloody or non-bloody D, severe GI bleed
o Heart: ischemia, heart failure (from HTN)
o Muscle: myalgia, weakness
• PAN PE, labs, dx:
o PE: Skin, neuro, GI, occult blood
o Lab: ↑WBC, mb proteinuria, hematuria
o Most labs to r/o other causes of vasculitis
o Dx: bx
• MCTD:
o overlap syndrome
o features of SLE, scleroderma, PM
o (+) distinctive Ab U1-RNP
• MCTD ssx:
o Early: General malaise, arthralgias, myalgias, ↓ fever; Raynauds
o Fever of unk origin
o Arthritis: more severe than SLE, mb deforming/destructive
o Myositis: no ↑ CK
o Heart: all 3 layers (pancarditis?)
o Lung: pleural effusions, infx, HTN, more
o Renal: mild nephropathy
o GI: ↓motility (like scleroderma)
o CNS: less severe than SLE. CN5 neuropathy, HA
• MCTD labs:
o Anti-U1-RNP (+) o ANA:↑titer speckled o Hemagglutin: ↑ titer o RF + 70%, CCP +50% o hypergammaglobulinemia \Anemia o Leukopenia
• MCTD dx:
o Alarcon-Segovia criteria probably best
o Anti-U1-RNP w ↑titer hemagglutination >1:1600
o 3+/5: Swollen hands, synovitis, myositis/myalgia, raynauds, acrosclerosis
• Spondyloarthropathies:
o =arthritis assoc w spondylitis
o =family of related dos: AS, PsA, ReA, enteropathic (IBD), undifferentiated (USpA), mb Whipple dz and Behcet dz
o enthesitis
o HLA-B27 (+)- not causative but often assoc
• Populations HLA-B27 (+):
o Healthy whites: 8% o Healthy AA: 4% o AS (whites): 92% o AS (AA): 50% o ReA: 60-80% o PsA: 60% o EA: 60% o Isolated acute anterior uveitis: 50% o USpA: 20-25%
• AS, epidem:
o chronic, painful, progressive inflam arthritis
o mostly spine and SIJ w pain and progressive stiffness
o M > F 2:1
o 15-30 yrs
o 10-20% ↓ 16 =JAS
o Mc Vikings, lc near equator
• AS etio:
o HLA-B27+ in 90-95%
o Cytokines: ↑TNFa, IL-12, IL-23 (causes enthesitis)
o Infection? Klebsiella Abs ↑ w AS than controls
o New bone formation uncoupled from inflam processes
• AS ssx:
o Inflam back pain (low) o Fatigue o Morning stiffness o hips and shoulders (pain) o peripheral enthesitis & arthritis o constitutional o organ-specific extra-articular manifestations: eyes, lungs, heart, peripheral jts o fever, ↓wt mb in periods of active dz
• inflam back pn of AS:
o mc sx, 1st manifestation in 75%
o Insidious onset, mos or yrs, usu at least 3 mos sxs before presentation
o Sxs improve w mod physical activity, worse w rest
o Diffuse nonspecific radiation to both buttocks
o Often stiffness and pain awaken in early morning (not a sx of mechanical back pain)
o Starts in SIJ → erosion, FUSION
o → LS region proximally, calcification of anterior longitudinal lig → fusion of spine (bamboo spine)
• Peripheral enthesitis and arthropathy of AS:
o Peripheral in 30-50%
o Enthesitis of Achilles tendon insertion, plantar fascia on calcaneus or MT heads, base of 5th MT head, tibial tuberosity, superior and inferior poles of patella, iliac crest
o Hips, shoulders, AC, SC jts
o Asymmetric mono or oligoarthritis, usu legs
o Atlantoaxial subluxation
o mb TMJ involvement
• Extra-articular manifestations of AS:
o Uveitis: mc, 20-30% (red flag w arthritis= red eye)
o CV: ↓ 10%, usu w severe long-standing dz. mitral valve insufficiency (major), AV block, aortitis
o Pulm: restrictive lung dz in late-stage, costovertebral, costosternal involvement, ↓chest expansion (hypoventilation)
o Renal: Amyloidosis rare, w severe, active, and long-standing dz. IgA nephropathy
o Neuro: 2nd to fractured fused spine, hard to detect on xray. Cauda equina syndrome w long-standing dz
o GI: asx inflam proximal colon and terminal ileum, up to 60%
o Metabolic bone dz: osteopenia and osteoporosis w long-standing dz, ↑ risk fracture
• PE for AS:
o ↓spinal ROM (all directions), and SIJ o loss of lumbar lordosis o accentuation of thoracic spine (kyphosis) o stooped posture o ↓ chest expansion o shuffling gait
• Imaging/Testing for AS:
o First line: X-ray T spine, SIJ, hips, TMJ
o early T spine “shiney corners”, syndesmophytes, ankylosis of facets, “bamboo spine” late finding (only in elderly)
o MRI (more sens, do if sxs but x-ray (-)) SIJ, early dz, edema and erosions
o Slip lamp exam, eye pain/redness
• Grading x-ray SIJ for AS:
o 0: normal
o 1: suspicious changes, some hyperlucency around jt
o 2: minimal changes, more hyperlucency, more inflammation
o 3: pseudodilatation (appearance of widening), sclerosis (↑bone formation), osteitis, fluffy garbage
o 4: complete fusion of SIJ, erosions at acetabular w new bone growth, osteophytes
• Dx criteria for AS:
o Low back pain and stiffness > 3 mos, improves w exercise, not relieved by rest
o ↓ lumbar ROM in both sagittal and frontal planes
o ↓ chest expansion (by age and sex)
o Sacroiliitis grade ≥2 BL or 3-4 UL
• PsA, epidem:
o Arthritis assoc w psoriasis
o usu sero(-) oligoarthritis in pts w psoriasis (5%), more w Ps nail dz (nails are external view of bone health??)
o Lc but characteristic features of distal jt involvement and arthritis mutilans
o usu HLA-B27 (+), 50%
o FHx 50%, ↓incidence near equator
o 2.5% of pop; M=F, 35-55, juvenile form 9-11
• PsA etio, risks factors:
o Etio: unk, genes (HLA-B27), environ and immun factors
o Risk factors for psoriasis: smoking, obesity, stress (phys/psych), environ expos, recent infx
o Psoriasis usu begins with a stressful event
- what is the most sensititve imaging to find early sacrolitis?
- Where does Psoriasis like to hide?
o MRI
o Gluteal fold, scalp, behind the ears, peri-umbilical
• PsA ssx:
o Fever, malaise
o Psoriasis
o Synovitis like RA
o Arthritis: location depends on form
o Dactylitis: “sausage “ digits, dt fusion of flexor tendon sheaths
o Jt swelling, tender, warmth, ↓movt
o Nails: pitting (tangential light), transverse ridging, onycholysis, keratosis, yellowing, destruction of entire nail
• Types of PsA:
o Symmetric polyarthropathy: 50%, BL. most similar to RA, disabling in 50%
o Asymmetric oligoarthropathy: 35%, mild. DIPs. Not BL. little relationship bw jt and skin activity (other forms, topical skin tx usu help jt dz), mb small and large jts
o Arthritis mutilans: ↓ 5%, severe, deforming, destructive arthritis. can progress over mos or yrs →severe jt damage. Osteolysis w Opera glass hands deformity
o Spondylitis: stiff spine or neck, or hands and feet, like symmetric arthritis. (50% HLA-B27+) usu severe dz
• Labs for PsA:
o Non-specific o ANA (+) 47% o RF (-). (+) suggests RA and psoriasis (not PsA) o ↑CRP/ESR o ↑uric acid, dt ↑skin turn over o IDA dt desquamation of skin o HLA B27 (+) (spondylitis)
• Imaging for PsA:
o X-ray vary by form
o gross destructive changes of isolated small jts, peripheral arthritis mutilans, erosions, ankylosis, extensive bone resorption to cause “opera glass hands”, fluffy periostitis, atypical spondylititis w syndesmophyte formation, acro-osteolysis, “pencil in cup” appearance, asymmetric sacroiliitis, absence of osteoporosis
o MRI: sens for detecting sacroiliitis (even if no sxs), jt synovitis, erosions, enthesitis
• Classification criteria for Psoriatic Arthritis (CASPAR):
o Should be dx by dermatologist and rheumatologist
o Inflam msk dz: pain of jts, spine, enthesium, w erythema, warmth, swelling; prominent morning and resting stiffness
o w 3+ pts:
o Current psoriasis (2 pts, all others 1)
o Hx psoriasis (unless current)
o FHx psoriasis (unless current or hx)
o Any: Nail changes, dactylitis, juxta-articular new bone formation on radiographs, RF (-)
• PsA ddx:
o psoriasis, sero (+) inflam polyarthritis, RA, OA, gout, ReA, septic arthritis, AS, hemochromatosis, HIV infx
• Comorbidities of PsA:
o AIDS (HIV infx) assoc w more aggressive jt dz
o Infx of skin lesions may → sepsis or septic arthritis
o Atlantoaxial instability
o Cosmetic and functional deformity
o Destructive crippling arthritis
o Depression often present
o Pain
• Reactive arthritis, epidem:
o = arthritis after infx, but pathogens cannot be cultured from affected joints o 3.5/100K o peak 15-35 o M:F 5-10:1 for STI o 1:1 for post-enteric onset
• ReA etio:
o Chlamydia trachomatis/pneumonia, Yersinia, Salmonella, Shigella, Campylobacter, E coli, C diff,
o Many are HLA-B27 (+), suggests genetic predisposition after sexual contact or exposure to enteric bacterial infx
• ReA ssx:
o Arthritis d-wks after infx (GI and GU are major)
o Usu mono- or oligoarticular, often legs (knees, ankles very common), very swollen
o Enthesopathy
o Dactylitis
o “Classic Reiter’s” (small %): conjunctivitis, urethritis, arthritis (can’t see, can’t pee, can’t dance w me)
o Conjunctivitis, st anterior uveitis
o GU: dysuria, pelvic pain, urethritis, cervicitis, prostatitis, salpingo-oophoritis, cystitis
o Oral lesions, mucosal ulcers
o Fever, malaise, HA, ↓wt
o Rashes (painful): keratoderma blennorrhagica, erythema nodosum
o Nail changes (not pitting)
o Genital lesions: circinate balanitis (painful)
o usu resolves in 3-4 mos but 15-50% have transient recurrences over yrs, sacroiliitis in 15-30%
• testing for ReA:
o Sero or other evidence of prior or current infx
o Mb ↑ESR, CRP
o HLA-B27 (+) (30-50%)
o Inflam synovitis on microscopy (r/o crystals, infx w gram stain)
o Imaging abn consistent w enthesitis or arthritis
• Enteropathic spondyloarthritis:
o Arthritis w IBD (Crohn’s or UC), 10-22%
o Arthritis may precede GI sx
o Not assoc w HLA-B27
• EA ssx:
o Pauciarticular, Asymmetric
o mb migratory
o Non-erosive
o Mb Dactylitis, Enthesitis
o Severity correlates w IBD activity
o Axial patterns are indistinguishable from AS
o Axial symptoms do NOT correlate w IBD activity
• Testing for EA:
o Often IDA (blood loss) or ACD o ↑CRP/ESR when active o RF/CCP/ANA (-) o Peripheral x-ray normal (bc non-erosive) o Hip x-ray may show jt destruction o Imaging of spine/SIJ similar to AS
