4/19 SLE, Systemic Sclerosis - Corbett Flashcards
SLE
basics
demographics
etiology x3
systemic lupus erythematosus
-
autoimmune disease mediated by tissue-binding autoantibodies and immune complexes
- deposition in tissues: heart, kidney, skin, etc
demographics
90% pts women, principally childbearing age (65% are b/w 16-55)
racial predisposition: AfAm/Caribbean
etiology
-
genetic factors
- family hx, monozygotic twin concordance
- HLA linkage
- inherited deficiency of early complement (C2, C4, C1q)
- lack of complement → imparied removal of circulating ICs by MNP system → favors tissue deposition!
-
immunologic factors
- failure of self-tolerance in B and CD4+ T cells → production of high-affinity pathoenic autoantibodies
- TLR engaged by nuclear DNA and RNA → activates B lymphocytes
- type 1 IFN play a role in lymphocyte activation
-
environmental factors
- UV light exposure
- gender bias due to actions of sex hormones, also X chromosome
- XXY males: 14x risk of SLE!
- drugs: hydralazine, procainamide, d-penicillamine can induce SLE-like response in humans
SLE model
strong assoc with defects in apoptotic clearance
- initiating events vary
- resulting excessive apoptotic debris has imp pathogenic effect
- antibodies are generated against nuclear antigens
ANA (anti-nuclear antibody): highly SENSITIVE for SLE, not v specific
- good rule out test
- not a great rule in test
anti-dsDNA and antiSm: highly SPECIFIC for SLE
autoantibodies
ANA (anti-nuclear antibody): highly SENSITIVE for SLE, not v specific
- good rule out test
- not a great rule in test
anti-dsDNA and antiSm: highly SPECIFIC for SLE
anti-dsDNA
- high specificisy
- titers fluctuate w disease activity
- high titer IgG anti-dsDNA abs → active glomerulonephritis
antiSm (nuclear non-histone proteins)
- not sensitive, HIGHLY SPECIFIC
- positive even when pt enters remission (levels can fall into normal range when quiescent)
- “speckled” pattern
mechanism of tissue injury
5steps
most systemic lesions caused by immune complexes (type III hypersensitivity)
- DNA-antiDNA complexes detected in glomeruli, sm blood vessels
- autoabs specific for RBC, WBC, platelets opsonize and promote phagocytosis/lysis
- antiphospholipid antibody
- loss of self tolerance
- production of autoab
- deposition of IC
- IC-assoc infl
- tissue fibrosis and damage
SLE presentation
young woman with…
- fever
- malar “butterfly” rash (photosensitive)
- arthralgia (symmetric polyarthritis)
typical SLE patient
Ps
characteristic rash: acute cutaneous SLE
degeneration fo basal layer of epidermis due to abs and IC at dermal-epidermal border
discoid lupus
nephritic disease
discoid lupus
- primary lesion: erythematous papulse or plaque (slight to moderate scale)
- hypopig in center, hyperpig at borders
nephritic disease
cardiac issues
- involvement of pericardium (effusions), myocardium, valves (sterile platelet vegetations → thickening of valves)
- “Libman Sacks endocarditis”: sterile platelet vegetations w high risk of embolic events, assoc with neuropsych SLE
SLE arthritis
- non-deforming (not erosive)
- issues due to lax tendons (not bone erosion)
- migratory
- symmetric, polyarticular problem (knees, carpal jts, finger jts)
- brief morning stiffness, mild synovitis
drug induced SLE
age of onset
racial pref
gender pref
dx abs
clinical findings
mortality
early death?
- active disease: renal, CNS issues
- infection: immunosuppression
SLE management
- immunosuppressive agents
- corticosteroids (flares)
- azothiaprine
- methotrexate
- cyclophosphamide
- biologics: being investigated
systemic sclerosis
(scleroderma)
4-5x more common: F>M
age at dx: 50yo
- chronic infl due to autoimmunity : CD4+ T ells responding to antigens accumulate in skin, release cytokines that activate infl cells and fibroblasts
- widespread damage to sm blood vessels
- intimal damage in digital arteries
- progressive interstitial and pervascular fibrosis in skin, multiple organs
vascular damage
capillaropathy
types of scleroderma
limited SSc
- distal to elbows, distal to knees, on face
- late visceral involvement
- benign clinical course
diffuse SSc
- all over
- early visceral involvement
CREST syndrome
form of ltd scleroderma
- calcinosis
- Raynaud phenom
- esophageal dysmotility
- sclerodactyly (distal to MCP joints)
- telangiectasia
key clinical ft of scleroderma
x4
two addtl systems
most common:
-
Raynaud phenomenon
- episodic exaggerated vasoconstr of sm arteries, arterioles, AV shunts, or thermoreg vessels of skin of digits (triggered by stress/cold)
- pallor → cyanosis → hyperemia (w return of bloodflow)
- be concerned if: starting brand new in middle aged female
-
skin changes
- progressive, insidious swelling of distal extremities (ex. fingers)
- gradual thickening of skin of fingers
- diffuse sclerotic atrophy of skin
- pitting, ulcerations at tips of fingers
-
swollen fingers and arthralgias
- arthralgias and myalgias are common → infl myopathy due to collagen deposition in muscle
- non-rosive arthritis affecting small joints
- ultimate loss of jt mobility is due to skin thickening/fibrosis
-
GER with or without dysmotility
-
esoph manometry totally flat: low peristalsis and LES resting tone also low → GERD!!!! w dysphagia
- atrophy of esoph sm muscl
-
esoph manometry totally flat: low peristalsis and LES resting tone also low → GERD!!!! w dysphagia
_*GI issues_
general bowel (large and small) dysmotility too - constipation alternative w diarrhea
- can develop SIBO
- associated with GAVE (gastric antral vascular ectasia) aka watermelon stomach
_*lung issues_
- inflammatory alveolitis → interstitial fibrosis
- early diffuse scleroderma in first 4yr illness
- anti-topoisomerase abs (anti-Scl70) predicts poor outcome
- pulmo vascular disease → pulmo a HTN
- longstanding disease in limited SSc
- prominent P2
key clinical ft of scleroderma
GI
pulm
renal
_*GI issues_
general bowel (large and small) dysmotility too - constipation alternative w diarrhea
- can develop SIBO
- associated with GAVE (gastric antral vascular ectasia) aka watermelon stomach
_*lung issues_
- inflammatory alveolitis → interstitial fibrosis
- early diffuse scleroderma in first 4yr illness
- anti-topoisomerase abs (anti-Scl70) predicts poor outcome
- pulmo vascular disease → pulmo a HTN
- longstanding disease in limited SSc
- prominent P2
*renal issues
- sudden onset malignant HTN (headache, visual disturbances, enceph w seizure, pulmo edema, pericardial effusion)
- hyper-renin
- risks: diffuse SSc, esp early; glucocorticoid tx (avoid in diffuse); RNA polymerase III abs
scleroderma renal crisis
scleroderma antibodies
negative-ANA → scleroderma v unlikely
- but not specific!
other antibodies:
-
anti-centromere ab
- limited SSc
-
anti-topoisomerase (antiScl70)
- highly specific for SSc (assoc w diffuse)
- assoc w interstitial lung disease and poor prognosis
-
antiRNApoly3
- rapid skin involvement
- scleroderma renal crisis
Sjogren’s syndrome
autoimmune disease presenting with sicca sx on mucosal surfaces
- xerophthalmia
- xerostomia
glands are destroyed → don’t make saliva/tears
determined by specific testing:
- ocular (rose bengal staining, Schirmer test)
- oral (salivary flow measurement, parotid scintigraphy)
relatively common
women (14-24x), 40-60
Sjogren’s
clinical features
histo hallmark
dry mouth due to decr saliva
- difficulty speaking
- incr dental decay
- difficulty swallowing
- oral candidiasis
dry eyes due to decr lacrimation
- gritty sensation
- blurred vision
- corneal ulcerations over time
hallmark: focal lymphocytic infiltrations of exocrine glands (check via biopsy)
concern with Sjogrens
frequent lymphadenopathy
complication: lymphoma! (44x incidence)
Sjogren’s clinical manifestations
Sjogren’s antibodies
- ANA antibodies (common)
- Rf (75%)
-
anti-ribonucleoprotein abs
- anti-Ro/SS-A and_or anti-La/SS-B are most specific
