autoimmune 2 Flashcards
multiple sclerosis is…
immune system attacks myelin of nerves → communication problems
NO CURE** paresthesia / motor weakness **
myasthenia gravis is…
chronic neuromuscular disease w varying degrees of weakness of skeletal muscles
THINK: T-cell immune response @ proteins in neuromuscular junction
** profound fatigue WITH skeletal muscle weakness **
ALS is…
amyotrophic lateral sclerosis
progressive incurable neurodegenerative disorder (“neuro failure” - motor neuron degeneration/death) / 3-5 year survival
ETC
- cortical motor cell loss + retrograde axonal loss- gliosis replaces lost neurons
- spinal cord atrophy + loss of large myelinated fibers in motor nerves
- intracellular inclusions in degenerating neurons & glia
idiopathic inflammatory myopathies are…
INFLAMMATION OF SKELETAL MUSCLES
polymyositis: “chronic inflammatory myopathy”
- SKELETAL muscle weakness
dermatomyositis: “connective tissue disease w inflammation”
- SKIN manifestation before muscle involvement
SEE: dermato w/ poly more often
systemic lupus erythematosis is…
immune system mistakenly attacks healthy tissue, often: skin, joints, kidneys, brain
** JOINT PAINT **
granulomatosis w/ polyangitis is…
aka Wegener’s
chronic inflammation of vessels = INHIBITS BLOOD FLOW = hypoperfusion
** sinusitis most common s/s **
polyarteritis nodosa is…
inflammatory vessel disease: necrotizing arteritis of MEDIUM VESSELS involving…
skin, peripheral nerves, mesenteric vessels, heart, brain
** PAIN prominent early s/s **
hereditary angioedema is…
genetic disease = edema of face, airways, internal organs
C1 INHIBITOR low or non-fxn
what is C1 + why is it important + which disease
C1 = bradykinins + inflammatory molecules
need C1-inhib or else excess levels
hereditary angioedema
arteritis
inflammation of arteries, usually d/t infection or autoimmune
MS progression
most: slow, progressive, secondary disease with steady neuro deterioration
85% = relapse/remit phases
5% = “benign MS” - largely asymp 10 to 15 years out
MS: more relapse/remission cycles = …
increased likelihood of advanced disease progression
MS s/s
paresthesia (37-45%) ← non-specificmotor weakness (20-27%) gait/balance disturbance (13-35%) vision loss/optic neuritis (15-17%) diplopia &/or vertigo (10-13%) hyperreflexia, extensor plantar response (babinski) LE ataxia impaired rapid alternating movements loss of vibration/proprioception
MS dx
dissemination in TIME
- 2+ attacks
OR
- gadolinium enhancing lesions (MRI) any time OR
- new MRI T2 enhancing lesion + prev doc lesion
dissemination in SPACE
- objective clinical evidence 2+ lesions
OR
- 1+ T2 lesion in 2/4 typical locations (periventricular, juxtacortical, infratentorial, SPINAL CORD)
primary progressive
1+ T2 lesions in at least 1 typical area
OR
2+ T2 lesions in cord
optional: positive CSF (oligo clonal bands and/or increased IgG)
** MS tx **
goal: decrease # cycles primary progressive: none (supportive care) relapse/remit: any of... - immunosuppressants - interferon beta
secondary pregressive: Mitoxantrone
** primary progressive MS tx **
none (supportive care)
nota bene interferon beta tx for MS
DOES NOT CROSS BBB
** secondary pregressive MS tx **
Mitoxantrone
myasthenia gravis s/s
PROFOUND fatigue WITH weakness (fluctuating skeletal muscle)
presenting: - ocular (50%)
- diplopia, ptosis- bulbar (15%) - dysarthria, dysphagia, mastication difficulties (speech: phonation, enunciation; esophageal persistalsis impaired, stricture)- Limb weakness (
what is bulbar
cranial nerves; head/face/neck in addition to respiratory
what is myasthenia crisis
acute respiratory failure usually assoc w/ severe bulbar symptoms
warning sx:↑ bulbar/generalized weakness & muscle fatigue (difficult to tell) ↑ dysphagia, difficulty masticating
warning symptoms of myasthenia crisis
↑ bulbar/generalized weakness & muscle fatigue (difficult to tell) ↑ dysphagia, difficulty masticating
** myasthenia crisis tx **
ICU: manage resp failure note: vent weaning difficult - weigh risk/benefit rapid tx: plasmapheresis OR IvG immunosuppressants: - glucocorticoids like methylpred (short term, follow with...) - mycophenolate - azathioprine - cyclosporin
myasthenia crisis immune suppressant meds
- glucocorticoids like methylpred (short term, follow with…)
- mycophenolate- azathioprine- cyclosporin
myasthenia dx x4
- ice pack (+ = improved sx)
- tensilon (+ = no changes in sx)
serologic: - MUSK antibodies
- AChR
-ab
electrophysiologic - MG + = ↓ nerve stimulation
** meds that may aggravate myasthenia **
NMB **ABX - aminoglycosides* - clindamycin - fluoroquinolones - vanc CV - BB - procainamide
MISC
- Mg (supplementation, etc)
- choloroquine/hydroxychloroquine
- botulinum
gliosis significance
hypertrophy/proliferation of varied neural cells - nonfxnal patch, like scar tissue occurs in ALS - replaces the dead nerves
ALS s/s
limb: spasticity, hyperreflexia, stiffness + movement incoordination, weakness/gait disorder, muscle atrophy/fasciculation
bulbar: jaw stiffness, dysphonia, dysphagia, laryngospasm, sialorrhea (drooling)
axial: neck weakness, bent spine, absent abdominal reflexes, ↑ lumbar lordosis
respiratory: tachypnea, weak voice/speech, weak cough, accessory muscle use ; → resp failure
ALS dx
only need 1 of the following / suspect = DNA test or electrodiagnostic study
- electrodiagnostic study
- genetic testing
- muscle biopsy: CONFIRMS
- MRI
- neuromuscular US
- labs: creatinine kinase (non-specific neuromuscular dysfxn), hypercalcemia (hyperparathyroidism), HIV/heavy metals (r/o ALS)
mainstay of ALS dx + what confirms
electrodiagnostic study
muscle biopsy confirms
ALS tx
tx is symptomatic!
- multidisciplinary care to maintain best QoL- general care: sialorrhea, thick mucus, resp failure, trach/bronch toileting- dysphagia- weakness, spasms, pain, loss of fxn- palliative vs hospice
dermatomyositis is…
one of the idiopathic inflammatory myopathies
skin manifestations prior to development of symmetric & proximal muscle weakness
idiopathic inflammatory myopathy patho/facts
gradual progression of weakness (takes weeks to months)
30 - 50, female, AA, usually assoc with other connective disease (scleroderma, SLE, Sjogren)
UNUSUAL TO SEE ALONE
polymyositis s/s
abrupt presentation
GRADUAL weakness- proximal muscle groups (UE, LE, neck, includes esophagus/dysphagia!)
- LEG precedes arm weakness
polymyositis weakness nota bene
abrupt presentation
GRADUAL weakness
LEG precedes arm weakness
dermatomyositis s/s
dusky red rash; malar (mimics SLE)
surrounding facial erythema beyond malar (+ neck, shoulders, upper chest/back “shawl sign”)
heliotrope eruption: periorbital edema + purple suffusion over eyelids
periungal erythema + dilation of nail bed capillaries
erythema over PIP & MCP joints (Gottron sign)
scalp involvement (mimics psoriasis)
heliotrope eruption
periorbital edema + purple suffusion over eyelids
DERMATOMYOSITIS
Gottron sign
erythema over PIP & MCP joints DERMATOMYOSITIS
dermato & poly common s/s
antisynthetase syndrome: inflammatory arthritis
Raynaud phenomenon
“mechanics hands” (lotion doesn’t work ; not gangrenous)
ILD
idiopathic inflammatory myopathy dx
ONLY SPECIFIC DX TEST: biopsy of affected muscle
MRI - detects early/patchy muscle involvement + guides biopsy
usually normal: CPC, troponin, ESR, CRP)
non-specific: ANA
rheumatoid factor: pos in 50%proteins
wtf like I’m going to remember these- Myositis specific autoantibodies
- Anti-Jo
- 1(anti-synthetase)
- Anti-SRP (signal recognition particle)
- Anti-Mi-2 (nuclear helicase)
only specific dx test for idiopathic inflammatory myopathies
biopsy of affected muscle
** idiopathic inflammatory myopathy management **
methotrexate: drug of choice!corticosteroids (NOT prednisone) 40 - 60 mg daily, lifelong
azathioprine, mycophenolate
last resort: immunoglobulin, rituximab
SLE s/s
JOINT PAIN (90%)
Raynauds (20%)
arthritis, fever, malaise, anorexia/weight loss
ocular: conjunctivitis, cotton wool spots on retina, photosens
malar rash, discoid rash, oral ulcers, serositis
renal: proteinuria gt 0.5 g/d OR dipstick >3+ ; casts
neuro: seizures, psychosis
heme - hemolytic anemia, leukopenia (lt 4K /mcL), lymphopenia (lt 1500/mcL), thrombocytopenia (lt 100K/mcL)
immunologic disease: positive ANA
pulmonary (pleurisy, Effusions, Bronchopneumonia, Pneumonitis, restrictive lung disease)
** major s/s with SLE **x3
JOINT PAIN! (90%)
Raynauds (20%)
restrictive lung disease
SLE most often used dx tests
ANA (98%) - non-specificanti-dsDNA (70%) - fluctutates w disease activity/glomerulonephritis
SLE dx tests (all)
ANA (98%) anti-dsDNA (70%)Antihistone (70%) - more r/t drug inducedAntierythrocyte (60%) - erythrocyte basement membranes; some hemolysisAntiphospholipid (50%)Lupus anticoagulant/LA (7%)CBC: anemia, leukopenia, thrombocytopeniaESR,CRP (nonspecific), UA (proteinuria, casts, hematuria), CrGFR (lupus nephritis), C3/C4 (decreased levels = active lupus)
** SLE main rx tx ** x2
Hydroxychloroquine 200 to 400 mg/d
Chloroquine
SLE all rx tx
MAIN Hydroxychloroquine 200 to 400 mg/d Chloroquine ADDITIONAL - corticosteroids (burst therapy) - immunosuppressants: mycophenolate, azathioprine, csa - antineoplastic: cyclophosphamide - B-cell MABS: -umab
SLE mgmt
- Hydroxychloroquine 200 to 400 mg/d
- Chloroquine
supportive care - lifelong anticoag if antiphospholipid syndrome
- acetaminophen (fever)
- COX2 inhib (chronic muscle pain - AVOID OPIOIDS)
- allogenic mesenchyma SC
T- vaccinations- limit tobacco- cancer screenings
granulomatosis w/ polyangitis mortality
fatal less than 1 year if not treated
granulomatosis w/ polyangitis s/s
sinusitis (most common)
- saddle deformity- necrotizing granulomatous lesions in U(90%)/L(60%) resp tract - vasculitis of SMALL - spontaneous VTE- new HTN- otitis media- polyarteritis nodosa- glomerulonephritis (75%; can progress to CKD in weeks)- tissue bx- chest CT
granulomatosis w/ polyangitis: see this and progress to what
glomerulonephritis (75% can progress to CKD in weeks)
** granulomatosis w/ polyangitis: test of choice **
ANCA (anti-neutrophil cytoplasmic autoantibodies)- against proteinaise-3 and MPO-ANCA- high sensitivity- positive or negative, doesn’t correlate with severity
granulomatosis w/ polyangitis: mgmt
prednisone 1 mg/kg/d - for flares! long term possible but remember: SE!!!
Cyclophosphamide 2 mg/kg/d- good longterm, can pair w pred for acute- malignancy riskAzathioprine up to 2 mg/kg/dMethotrexate 20-25 mg/wkRituximab
granulomatosis w polyangitis VS polyarteritis nodosa
gwp: SMALL vessels
pn: MEDIUM vessels
polyarteritis nodosa
INSIDIOUS ONSET
PAIN PROMINENT early
- pain: bigger vessels, arthralgia, myalgia, neuropathy- fever, malaise, wt loss, develop for wks- mononeuritis multiplex– foot drop ← abnormal, not disuse syndrome; progressive gait issues Skin: Livedo reticularis, subcutaneous nodules, LE ulcerationsAbdominal pain: N&V, acalculous cholecystitis , appendicitis, perforation, micro-aneurysm ruptureSubclinical cardiac
polyarteritis nodosa: dx
tissue biopsy (70% sensitivity)
polyarteritis nodosa: tx
prednisone - up to 60 mg/dpulse methylprednisolone - 1 gm/d/3daysimmunosuppressants: cyclophosphamide (cytoxan)
hereditary angioedema usually triggered by
illness, stress
foot drop associate with which autoimmune
polyarteritis nodosa
hereditary angioedema: dx
- C1
- C1 esterase inhibitor low or non-fxnal
- C2 level (correlates with severity of disease)
- normal C4 activity rules out HAE
- CT scan
hereditary angioedema: mgmt
antihistamines DO NOT WORK- pain meds & fluids
- C1 esterase inhibitor concentrate (derived from human plasma)- FFP - contains C1 inhibitor (not as good as concentrated C1 esterase inhibitor)- Ecallantide - ⊣ plasma kallikrein (consult!!!)- icatibant - bradykinin B2 receptor inhibitor (Europe)- androgens - danazol: ↑ production C1 inhibitor
rules out hereditary angioedema
normal C4 activity
