Flashcards in Dr. P Deck (97):
Antiphosphoipis antibodies are a family of autoantibodies against _____.
Phospholipid binding plasma proteins, B2-gp-I
Clinical manifestations of anti-phophoslipid
asymptomatic to catastrophic, Arterial=stroke, venous=DVT, loss of preg post 10 wks,
What are catastrophic APS?
rare, mutltiple thrombosis of medium and small arteries over days
How do you make diagnosis of APS?
presence of characteristic clinical manifestations and persistently positive aPLs 12 wks apard
A common strategy to prevent fetal loss in aPL positive patients is ____
low dose aspirin and heparin
Primary thrombosis prevention in persistenly aPL positive pt?
risk-stratified: eliminate reversible thrombosis risk factor and prophylaxis during high risk periods
Clinical features suggesting APS
livedo reticularis, thrombocytopenia, myelopathy
Diffuse connective tissue diseases are usually associated with autoimmunity to what?
sliceosomal components (U-RNPs)
nucleosomal (nucelosomes, histones, DNA)
proteosomal (HC9, LMP2)
_____ of molecules often renders them more antigenic in overlap syndromes.
The evolution of symptoms of overlap syndromes may be associated with ______.
mimcry and epitope spreading
What are undifferentiated connective tissue disease?
early stages of many autoimmune CT disease. 50% remain undifferentiated.
Important clues about the eventual direction of differentiation of UDCT can be obtained from ______
nail-fold capillary microscopy, auto-antibody profile, clinical manifestations
What is MCTD?
prototype- lupus, scleroderma, myositis--- takes years to develop
The most common presentation of MCTD is ____.
MCTD is most commonly associated with antibodies to_____. This means what?
u1-rnp...... predicts lack of severe renal and CNS involvement
What is the major cause of death of MCTD?
Nearly all pt with UCTD have ______.
raynaud's and unexplained synovitis
What auto-antibodies predict what from UCTD?
Synthetase and Pm/Scl--> myositis overlap
Scleroderma overlap syndromes include scleroderma overlap syndromes:
calcinosis, raynauds, esophageal involvement, sclerodactyly, telangietasia, CREST, mysositis associated with sclerodactyly, and MCTD
_____ is often the first clinical feature of SSc overlap syndromes.
The finding of _______ on the nail capillary fold bed and pathologic autoantibodies are important clues about the development of overlap syndrome.
thickened and dilated capillaries
CREST has a common overlap with _____.
primary biliary cirrhosis
______ are the main causes of morbitiy of scleroderma overlap syndromes.
pulm fibrosis and HTN
Which is more common, mysositis overlap or classic PM or DM?
_______ are associated wth myositis, arthritis, ILD
amino-acyl tRNA synthetase ab
Order of appearance of bad things in ARS
arthritis and ILD first, then myositis
What AB in MOS tend to mean corticosteroid unresponsiveness?
What ab in MOS mean corticosteroid responsivenss?
U1-RNP, PM/Scl, Ku
What ab in MOS mean malignancy?
155-kd and 140-kd proteins
What serious effects are associated with MCTD?
renal- 1/4 get membranous GN
CNS: rare, trigem neuropathy and senso-hearing loss
Which type of Raynauds is associated with other disease?
Sjorgrens syndrome is divided into what forms? How common?
primary and secondary- Primary .1-.6%
What are the clinical hallmarks of Sjorgrens?
keratoconjunctivitis sicca/dry eyes, xerstomia/dry mouth, parotid swelling
What are extraglandular features of Sjorgrens?
fatigue, raynauds, polyarthralgias, ILD, neuropathy, purpura, renal tubular defects
_____ is the characteristic histo finding for Sjorgrens?
mononuclear cell infiltrate of lacrimal and salivary glands
How do you diagnose Sjorgrens?
dry eyes/mouth assessment, ANAs- antiRo/SS-a and anti-La/SS-b, labial salivary gland biopsy
What is the point of treated Sjorgens?
symptom management and control of extraglandular disease
Epidemiolgoy of Sj. Syn.
middle aged woman with increase autoimmunity in the fammily
What is the relationship between SjSyn and lymphoma?
44 times increase risk
Immunological features of Sj.Syn.
Hypergammaglobulinemia, FANA, RF, Anti-Ro and La
_____ are a heterogenous group of muscle diseases characterized by symmetric proximal muscle weakness and frequent involvement of other organs.
Myopathies are often accompanied by elevated levels of ________ and _____.
serum muscle enzymes and abnormal electromyograms
What does histology show with myopathies?
varying degrees of inflammation and muscle fiber degernation and generation
_____ are common therapies in myopathies.
Corticosteriods and cytotoxic drugs
What antibodies could be present in myopathies?
molecules involved in protein synthesis
What haplotype is found in a significant portion of IBM patients?
B8, DR3, dr52, DQ2
How is the cell mediated immune response different between Dm and Pm and Ibm?
DM: perivascular, Cd4, macs, dendritic cells
others are CD8 prominant
_____ results from chronic and recurrent activation of the immune system with production of Ab and other protein products contributing to inflammation and tissue damage.
What is typical epidemiology of SLE? What does this mean?
black female in child-bearing years- there may be a role for both hormone and sex-related factors
Describe what genetic analysis shows for SLE.
Complement def. confer the highest risk. Mutuations in TREX1 point to imparied regulation of nucleic acids. Most variants that increase SLE are related to innate and adaptive immune response.
Role of enviornmental factors with SLE
initation and flare ups
The discovery of _____ has showed importance of innate immunity in SLE.
Role of nucleic-acid immune complexes in SLE
serve as stimuli for TLR
Role of IFN in SLE
production of IFN as emerged as central mechanism of lupus
Additional pathogenic effectors of SLE
platelets, neutrophil, complement
Clinical manifestations and how to make a formal diagnosis of SLE
RASH PAIN O MD (renal, arthritis, serositis, hematologic, photosens., ANA, Immunologic, neurologic, oral ulcers, malar rash, discoid rash) 4/11
What are the general, constitutional symptoms of SLE
fever, fatigue, weight loss
____ is the most common subtype of CCLE.
Malar region butterfly rash is ______.
Is lupus arthritis symmetrical or not?
Describe lupus arthritis
symmetrical, deforming, non-erosive
What is Jaccoud's arthropathy?
SLE, lookes like RA, no erosions on radiographs
Describe SLE renal pthogenesis
significant morbitiy, 50% of SLE pt, coreelated with anti-DNA, immune complex can be deposited or form in situe
Anti-body directed cellular cytotoxicity is responsible for what in SLE?
hemolytic anemia, immune thrombocytopenia, vasculitis
Are SLE pregnancies considered high risk?
yes(fetal loss, small fetuss, neonatal lupus)
What is pediatric onset-SLE associated with?
Strategies to decrease impact of SLE comorbid infections.
1. educate phys/pat 2. immunize 3. minimize GC exposure 4. prompt therapy
What is the target GC dose for SLE?
.25 mg/kg every other day for 2-3 months
_____ are effective for skin and mucocuatneous manifestations of SLE. Their ues has been associated with reduced organ damage.
_____ is effective in mild to moderate SLE including nephritis.
What is the standard of care for severe SLE with major organ involvement?
CYC and GC
What is mmf used for?
equally efficient and better tox profile than CYC for moderartely severe PLN
T or F, Calcineurin inhibitors and rituximab are used in refractory lupus nephritis.
How do you control SLE skin manifestations?
prevent sun exposure, anti-malarials, topical GC
In moderately severe PLN, ______ may be preferred as induction regiment when gonadal tox is concern.
What may be used in maintenace therapy after induction with severe lupus
AZA or mmf
______ are necesary in pt with APS to prevent recurrent events.
What is used for neurpsychiatric events of SLE though to be due to inflammatory process?
GC +/- IS
___ has a complex pathogenesis and protean clinical manifestations reflecting the underlying early immune dysregulation and microangiopathy as well as a systemic fibrosis.
Is there marked pt-pt variability is Scleroderma?
In scleroderma, vascular lesions in ___ blood vessels occur early and progress to _____.
small, obliterative vasculopathy that causes tissue hypoxia, oxidative stress, and vascular complications
What does genetic analysis say about sleroderma?
role of HLA and other immunoregulatory genes that are also associated with lupus
____, ____, and _____ is prominent in scleroderma but roles undetermined as primary factory.
immune dysregulation manifested by ab, evidence of innate immune activation, interferon signature
What is fibrosis associated with in scleroderma?
sustained mesenchymal cella ctivation by grwoth factors, cytokines, chemokines, hypoxia, ROS, abberaant reactivation of developmental pathways
T or F Systemic sclerosis is a mutlisystem connective tissue disease affecting the skin and internal organs.
____ disease process is characterized by chronic inflammatoin with variable degrees of collagen accumulation in affected tissues and obliterative vasculopathy of peripheral and visceral vasculature.
What is the difference between early limited and diffuse scleroderma
Limited: Raynauds only for years. general symptoms are rare, minmal arthralgia, puffy FINGERS, limited skin thickening, anti-centromere
Diffuse: raynauds delayed, acute onset of lots of symtpoms, lots of arthtralgias including carpal tunnel, swollen HANDS, early diffuse skin, anti-scl70, anti-RNA pol3
Describe GI problems in systemic sclerosis
manifestations of gut dysmotility are universally present in scleroderma and can affect anywhere in tract, though upper is more common and can be severe. Dysfunciton and failure of lwoer GI is associated with poor prognosis
Is lung disease a major cause of morbitidy in scleroderma?
Does pulmonary fibrosis occur in diffuse and limited sclerosis?
yes- variable in prognosis and severity
______ has the worse prognosis with ILD in scleroderm.
nonwhites an anti-topo1 positive pt
Tx for scleroderma drelated ILD
What are risk factors for scleroderma lung
late onset of slceroderma, limimted phenotype, lots of telangtasia, positive anti-centromere ab
The degree of lung fibrosis on ______ predicts outcom
Scleroderma renal crisis in a life threatening condition that occurs ____.
in 5-10% OF PT
What are risk factors for scleroderma renal crisis
early diffuse skin disease, use of corticosteroids, anti-RNApol3