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37 Cards in this Set
- Front
- Back
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Wegener's granulomatosis
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- granulomatous vasculitis of small arteries and veins
- characterized by focal necrotizing vasculitis, necrotizing granulomas in lung and upper airway, & necrotizing glomerulonephritis (pauci immune) - age: 25-60 - c-ANCA (anti-proteinase 3) - purpura, hemoptysis - treat w/ cyclophosphamide + prednisone |
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Polyarteritis nodosa (PAN)
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- necrotizing vasculitis of small and medium-sized muscular arteries
- age: 20-70 - GI vasculature, renal artery, extremities - angiogram shows lots of aneurysmal dilatations - mononeuritis multiplex, digital gangrene - associated with HBV - treat w/ cyclophosphamide + prednisone |
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Giant cell arteritis
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- vasculitis of medium and large arteries
- age: >50, mostly in Caucasians, more common in women - involves thoracic aorta and major branches, esp. the extracranial branches of carotid artery - pathogenesis begins in adventitia, migrates to media - fever, anemia, high ESR - headache, jaw claudication, impaired vision (--> irreversible blindness) - 1/2 of pts have systemic involvement and polymyalgia rheumatica - treat w/ prednisone |
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Henoch-Schonlein purpura
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- systemic vasculitis of small vessels
- mostly in kids (age 5-7), male/female ratio 1.5/1 - palpable purpura, arthralgias, GI symptoms, glomerulonephritis (w/o destruction of vasculature) - good prognosis, resolves spontaneously |
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Ankylosing spondylitis
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- inflammatory disorder affecting axial skeleton
- >95% of pts have HLA B-27; susceptibility mostly genetic - affects spine and proximal large joints - insidious onset, age 10-25; starts in lumbar region and ascends progressively - treat with anti-TNF-α drugs |
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Psoriatic arthritis (PsA)
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- spondyloarthritis + psoriasis
- enthesitis, DIP joint arthritis ("pencil in cup"), onychodystrophy, dactylitis (sausage digits) - 10-20% of psoriasis pts develop, over 0-20+ years after onset of psoriasis - ~15% of pts did not have prior psoriasis - very strong genetic inheritance; HLA B27 and B39 predispose - arthritis mutilans: only develops in <5% - treat with anti-TNF-α drugs |
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Psoriasis
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- autoimmune disease of skin; tends to involve extensor surfaces
- MHC class I presentation of keratinocyte peptides --> retardation in keratinocyte differentiation induced by activated T cells - onset age 15-30 - psoriasis susceptibility HLA haplotypes - 10-20% of pts develop PsA, 0-20+ yrs after onset of psoriasis |
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Reiter's syndrome / Reactive arthritis (ReA)
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- spondyloarthritis that follows infection
- HLA-B27 predisposes - several joints develop synchronous, highly inflammatory, asymmetric arthritis - "can't see, can't pee, can't climb a tree": (1) conjunctivitis and anterior uveitis, (2) urethritis, (3) arthritis - enthesitis, dactylitis, sacroiliitis, stuttering spondyloarthritis - symptoms also in nails, eyes, urogenital area, heart, skin - caused by GI or chlamydia infections |
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Rheumatoid arthritis (RA)
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- destructive articular disease; most common primary inflammatory arthropathy
- involvement of TH1 cells, macrophages, and B cells - prevalence of 1% - age of onset 30-50 yrs - female:male, 3:1 - MHC class II DRβ1 alleles --> increased risk - rheumatoid lung, rheumatoid vasculitis, Felty's syndrome - DMARD therapy |
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Rheumatoid factor
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- IgM antibody with specificity for the Fc region of IgG
- found in certain diseases: RA, SLE, Sjogren's syndrome, HCV, HIV, SBE, TB, syphilis, leprosy, lymphoproliferative disorders - present in 3% of general population |
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Anti-cyclic citrullinated peptide (anti-CCP) antibodies
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- antibodies generated against proteins found in pts with RA
- these proteins, derived from the synovial tissue, exhibit enhanced citrullination - ELISA assay: sensitivity for RA is 70%, specificity 95% |
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Diagnosis of RA
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- morning stiffness, symmetric polyarticular arthritis, arthritis of hand joints (but never DIP), rheumatoid nodules, periarticular demineralization and marginal erosions
- rarely involves shoulders, hips - rheumatoid factor: 70% sensitivity, 60% specificity - anti-CCP antibodies: 70% sensitivity, 95% specificity |
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Rheumatoid lung
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- develops in some RA pts
- extension of inflammatory process --> fibrosis --> lung reduction/restriction |
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Felty's Syndrome
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- RA + neutropenia + splenomegaly
- in 1-2% of RA pts - increased risk of infections and non-Hodgkins lymphoma |
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DMARD therapy
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- Disease-Modifying Anti-Rheumatic Drug therapy--for RA
- NSAIDs - methotrexate- usually given with anti-TNF agent - anti-TNF agents - B cell depleting agent (rituximab- anti CD-20) - costimulatory inhibitor (abatacept- anti-B7) |
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Anti-TNF agents
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- mostly monoclonal antibodies to TNF-α
- used to treat autoimmune diseases - generally well-tolerated - adverse effects: reactivation of latent TB - etanercept (binds to and neutralizes TNF) - monoclonal ab: infliximab, adalimumab, golimumab, certolizumab |
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Rituximab
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- chimeric human-murine monoclonal ab targeting CD20 expressed on B cells
- CD20 only expressed from pre-B cells to mature B cells, not plasma cells - causes complement activation and ADCC to kill B cells - can be used to treat RA with methotrexate - IV infusion every 6 mos.--half life of 2-3 weeks but B cell depletion lasts 4-6 mos. |
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Etanercept
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- binds to and inactivates TNF
- recombinant soluble TNF receptor formed by fusion of 2 human TNF receptors + the Fc portion of IgG - subcu injection; half life of 4 days |
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Infliximab
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- chimeric IgG monoclonal ab specific for TNF-α
- IV infusion every 8 weeks to treat RA; given with methotrexate to inhibit development of ab against murine regions |
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Adalimumab
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- fully humanized monoclonal ab specific for TNF-α
- subcu injection every 2 weeks to treat RA; given w/ or w/o methotrexate |
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Anakinra
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- human recombinant form of IL-1 receptor antagonist--blocks effects of IL-1
- daily subcu injection (half-life of 6 hours)--very modest efficacy in RA |
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Abatacept
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- binds to B7 of APC --> prevents costimulatory signal to T cells
- IV infusion every month to treat RA - used with cyclophosphamide to treat SLE |
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Systemic Lupus Erythematosus (SLE)
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- auto-antibodies form against ubiquitously expressed nuclear and cytoplasmic components
- possible mechanisms: impaired clearing of apoptotic bodies leading to generation of self-antigens, failure of negative selection of T cells - M:F, 1:10 - markers: ANA, anti-dsDNA ab, pro-clotting ab - complement deficiency = #1 genetic association w/ SLE; also, MBL polymorphisms |
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ANA
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- antinuclear ab
- hallmark of SLE - look for pattern of nuclear staining - positive in >95% of SLE pts - cancer and TB can also produce positive tests |
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Lupus glomerulonephritis
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- kidney is most targeted organ in lupus
- class II: mesangium lights up with Ig and complement - class III: focal proliferative--more cellularity and more widespread deposits - class IV: diffuse proliferative; >50% glomerular involvement - class V: diff process--more proteineuria--can co-exist with II, III, or IV - class VI: advanced sclerosis |
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Diagnosis of SLE
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- can only be discriminated from other diseases
- I'M DAMN SHARP: Ig (anti-dsDNA, anti-Sm, antiphospholipid), Malar rash, Discoid rash, ANA, Mucositis (oropharyngeal ulcers), Neurologic disorders, Serositis (pleuritis, pericarditis), Hematologic disorders, Arthritis, Renal disorders, Photosensitivity - also: constitutional symptoms, Reynaud's phenomenon, vasculitis, alopecia, antiphospholipid syndrome - look for ANA, anti-dsDNA ab, pro-clotting ab |
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Antiphospholipid syndrome (APS)
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- dx requires antiphospholipid ab at 2 time points and documed clot or pregnancy loss
- ab present in 25-40% of SLE pts - livedo reticularis = classic rash --> thrombosis |
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Treatment of SLE
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- target therapy to currently involved organs
- corticosteroids - cyclophosphamide - mycophenolate mofetil - azathioprine - cyclosporin/tacrolimus - best therapies target T cells, not B cells |
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Scleroderma
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- vasculopathic mechanism --> collagen deposition --> fibrosis of target organs
- limited vs. diffuse subtypes - almost always involves hands and feet - skin: shiny, somewhat contracted, with areas of depigmentation - sclerodactyly, preceded by Raynaud's phenomenon in >97% of pts - facial telangiectasias - pulmonary disease is major cause of mortality - markers: anticentromere ab, anti-Scl-70 ab (diffuse), anti-RNA polymerase ab - HLA DRβ1 association - F:M, 3:1; African-Americans > caucasians (2:1) |
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Limited scleroderma
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- CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
- involves face and skin distal to elbows and knees - associated with anticentromere ab - 90% 5 year survival, 75% 10 year survival |
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Diffuse scleroderma
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- involves face, skin of proximal extremities, and trunk
- affects kidney, lungs, heart, GI (replacement of sm muscle with collagen --> loss of function) - associated with anti-Scl-70 ab - 70% 5 year survival, 50% 10 year survival |
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Raynaud's phenomenon
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- vasospasm of digital microvasculature --> digital ischemia (pallor), digital hypoxia (cyanosis), and digital reactive hyperemia (erythema)
- early manifestation of scleroderma in >97% of pts |
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Scleroderma kidney disease
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- exclusive involvement of small renal arteries and arterioles--doesn't affect glomerulus
- renovascular disease --> hypertensive crisis - early manifestation of diffuse scleroderma - prevent/treat with ACE inhibitors |
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Treatment of pulmonary hypertension in scleroderma
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- Ca channel blockers (diltiazem)
- endothelin receptor blockers (endothelin causes vasospasm) - phosphodiesterase 5 inhibitor (sildenafil) - prostacyclin analogs (require daily admin, mostly given IV--labor intensive) |
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GI involvement in scleroderma
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- GERD (treat with proton pump inhibitors)
- hypomotility - bacterial overgrowth --> malabsorption (treat with antibiotics) - pseudo-obstruction - diverticuli in colon |
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HLA B27
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- MHC class I allele associated with psoriasis, ankylosing spondylitis, inflammatory bowel disease, and reactive arthritis
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Anti-Scl-70 antibody
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- anti-DNA topoisomerase I ab
- associated with diffuse scleroderma |
