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systemic sclerosis (scleroderma)
- excessive extracellular matrix deposition
- result of autoimmunity, vasculopathy, (early stages) and fibrosis (late stage)
- limited and diffuse forms
- vascular: endothelial cell damage/apoptosis, smooth muscle and pericyte proliferation leading to increased thickness, ROS, hypoxemia, vascular loss
- fibrotic: fibroblast differentiation to myofibroblasts (contractile cells), collagen overproduction, increased deposition, remodeling
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limited systemic sclerosis
- skin thickening/tightening only distal extremities (+face/neck)
- 60% of cases
- longstanding Raynaud's that can proceed onset
- mild fatigue and athralgias
- isolated pulmonary HTN, esophageal disease, telengectasias, calcinosis
- anticentromere antibodies
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diffuse systemic sclerosis
- 30% of cases
- skin thickening/tightening over whole body
- Raynaud's onset w/disease, sudden
- more severe fatigue, arthralgias, tendon friction rubs often present
- renal disease, interstitial lung disease, severe/diffuse GI, cardiac disease
- anti-Scl-70 antibodies
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Diagnosis of systemic sclerosis
- nailfold capillaroscopy: capillary loop dilatation and capillary loss
- digital tip ulcerations secondary to ischemia, digital pits/scars, gangrene, distal phalangeal tuft resorption
- anti-centromere Ab (for limited)
- anti-Scl-70 Ab (for diffuse)
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Vasculitis
- inflammation/autoimmunity targeted to endothelium
- occlusion of vessel due to thrombosis or loss of integrity
- immune complex deposition, ADCC, direct immune cell cytotoxicity
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small vessel vasculitis
- neuropathy
- non-blanching paplable purpuric lesions due to RBC extravasation
- RBC casts due to glomeruli damage
- Antineutrophil antibody (ANCA): activate neutrophils
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medium vessel vasculitis
- skin ulcer secondary to occlusions
- anneurysmal dilatations/stenosis
- post-prandial pain, GI bleed, perforation
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large vessel vasculitis
- Giant cell arteritis: disrupted internal elastic membrane, thickened temporal artery, limb claudication (ischemic pain w/exertion
- Takavasu's arteritis: limb claudication, thickening of carotids
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SLE (systemic lupus erythermatosus): clinical presentation
- Malar rash: sparing of nasolabial folds
- Discoid rash: follicular plugging, raised
- Photosensitivity: UV
- Oral/nasal ulcers: painless
- Arthritis: nonerosive, 2+ joints
- Serositis: pleuritis or pericarditis
- Renal disorder: proteinuria > 0.5mg/dL, 3+ casts
- Neurologic disorder: seizures/psychosis
- Hematologic: anemia, leukopenia, thrombocytopenia, lymphopenia
- Immunologic: anti-dsDNA, anti-Sm, anti-PL
- Antinuclear antibodies: ANA titer w/immunofluoresence
- 4 criteria present = 98% specificity, 97% sensitivity
- Class III, IV most severe
- > anti-dsDNA, < C3/C4 = more severe
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What is ADCC?
What are depleting/neutralizing antibodies?
- Antibody-dependent cellular toxicity
- antibodies directed against self-antigens, result in cell death
- depleting/neutralizing Abs against plasma cells/proteins - can form immune complexes
- Found in SLE
-
SLE: epidemiology and onset
- 51/100K in US, 9:1 female:male adults, 3:1 female:male children (sex hormone's role?)
- 16-55YO, African Americans, Hispanic
- UV light exposure, drugs
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SLE: ANA associations
- ANA: useful to rule out SLE, need subsets for diagnosis
- dsDNA: correlates w/disease activity, nephritis, specific and sensitive
- histones: drug-induced lupus
- Ro(SS-A): neonatal lupus, subacute cutaneous lupus
- La(SS-B): neonatal lupus also
- Sm: no associations, but very specific for SLE!
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SLE treatment
NSAIDs, steroids, antimalarials, immunosuppressives
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Sjogren's Syndrome: pathophysiology
- lymphocytic infiltration (CD4+, B cells) of exocrine glands
- extraglandular involvement: arthritis, B cell lymphoma, lymphocytic infiltration of organs, fatigue
- ANA, RF, anti-SSA, anti-SSB are not sensitive or specific diagnositically
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Sjogren's syndrome: glandular involvement
- dry mouth: dental problems, dysphagia, difficulty speaking in 90% of pts
- dry eyes (xeroophthalmia): keratoconjuctiva sicca - gritty sensation 95%
- dry tracheobronchal mucosa (xerotrachea): hoarseness, bronchitis
- dry skin, vaginal mucosa: puritis, increased infections
- major salivary gland involvement
- pancreatic exocrine, hypochlorhydria: epigastric pain, dyspepsia, atrophic gastritis
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