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Flashcards in Testing for Rheum Deck (62):

How are dxs made for rheum disorders?

- based upon criteria for classification of various rheum disorders:
clinical features (h and p)
lab/radiographic findings
- dx tests don't make the dx (they help confirm)
- dx tests modify the probability that a particular disorder is present


What is sensitivity?

- proportion of pts w/ positive test who have the disease - so a negative test will effectively rule out the disease


What is specificity?

- proportion of pts w/ negative test who don't have the disease - so positive test will effectively rule in disease


How do you screen for autoimmune disease?

- primarily by H and P
- increase your pretest probability by asking ?s that support the dx of inflammatory arthropathy or systemic rheumatic disease
- look for clues on physical exam


When should you order serologic testing?

- You should have a compelling reason to order rheum eval tests
- assist in confirming a specific dx (high index of clinical suspicion)
- formulate appropriate management
- eval/monitor disease activity


What are acute phase reactants?

proteins synthesized by the liver and induced by:
-inflammation: infections, autoimmune disorders, neoplasms
-tissue injury/necrosis: trauma, infarction

- parallels chronic inflammation, goes up and down w/ inflammation
- monitors disease activity
- not DX!
- coag proteins (I, II) fibrinogen levels inc, platelets inc
- complement components (C3, C4, B)
- many others: fibronectin, transport proteins (Hp, Transferrin, Ceruloplasmin)


What is the ESR?

- the distance at which erythrocytes have settled in a vertical column of anticoag blood in an hour (mm/hr)
- in an inflammatory state: positively charged acute phase proteins neutralize negative charges and allow RBC to aggregate
- now RBC fall at a diff rate, and a further distance - increased ESR
- indirect measurement of serum APR concentrastion, particularly fibrinogen
- influenced by size, shape, number of RBCs (ESR is increased in anemia)
- as a pt's condition changes the ESR changes relatively slowly


When would the ESR be increased?

- w/ age, slightly higher in women, preg, diabetes, renal failure, malignancy, tissue damage (MI, CVA)
- both ESR and CRP elevated in obesity: due at least in part to IL-6 secretion by adipose tissue
- acute phase reactants
- paraproteins
- anemia (fewer cells, less repellent forces)


Normal values for ESR?

- male: less than 17mm/hr
- female: less than 25mm/hr
- kids: less than 10mm/hr


Elevated ESR remains an impt dx criterion for which 2 rheumatic conditions?

- polymyalgia rheumatica: greater than 40 mm/hr
- GCA: greater tahn 90mm/hr


Uses of ESR in other rheum diseases?

- limited utility for differentiating inflammatory jt disease from noninflammatory jt disease: nondx
- not reqd for dx of RA: good hx and physical far more sig than ESR in establishing the dx, but ESR can be helpful in monitoring disease activity


What is CRP?

- acute phase protein produced by the liver:
produced in response to inflammation:
infections, long term chronic inflammatory illness
- enhances complement binding and phagocytosis
- acute increases w/in 6 hrs, peaks at 48 hrs
- 2 types of tests:
standard CRP
High-sensitivity CRP (hs-CRP)
- less sensitive than ESR to irrelevant factors (age, gender, anemia)
- responds more quickly
- more expensive, may not be available, don't always know how to interpret


Normal values of of CRP?

- in adults: less than 1 mg/L
- low grade inflammation: 1-10 mg/L
- systemic inflammation is greater than 10 mg/L


Use of ESR and CRP in rheum?

- nonspecific indicators of inflammation
- not useful as screening tests for rheumatic diseases
- can't differentiate one disease from another


What is the Rheumatoid Factor? Sensitivity? Specificity?

- an auto-ab directed against Fc portion of IgG
- sensitivity: 80% in pts w/ RA
- specificity: 80-90%
- prevalence of RA: 0.5-3%


What are other conditions that cause a positive Rheumatoif factor?

- scleroderma
- Sjogren syndrome
- cryoglobulinemia
- infections: Hep, TB, SBE, Syphilis, parasitic disease, viral (mono)
- pulm diseases (sarcoidosis)
- malignancy

- thus RF isn't dx for RA on its own, testing is most useful when there is a moderate level of suspicion for RA


What is the post test probablity?

- the probability that the pt has a disease given a positive test result
(should only get test if you have a high pretest probability)


Why does clinical impression count the most in dx RA?

- up to 30% of pts w/ RA are RF negative early in the disease


Normal value of RF?

- measured as a titer
- less than 1:80 is negative


What is the classificaiton criteria of RA?

- need a total score of at least 6
- number and site of involved jts (synovitis)
2-10 large jts = 1 pt
1-3 small jts = 2 pts
4-10 small jts = 3 pts
more than 10 jts = 5 pts
- serological abnormality (RF or anti-ccp ab):
low positive (above ULN)= 2 pts
high positive (over 3x the ULN)= 3 pts
- elevated acute phase response (ESR or CRP) above the ULN= 1 pt
- sx duration at least 6 wks = 1 pt


What does RF correlate w/ in pts w/ established RA?

- correlates w/ severe articular disease and extra-articular manifestations
- once test is positive there is no value in re-testing: RF doesn't change w/ disease activity


Use of RF?

- it isn't dx for RA
- the test's utility is greatest when there is a moderate pre-test probability of disease


What is the Anti-CCP? Use?

- citrulline ab, CCP abs
- ab directed against citrullinated peptide residues present w/ inflammtory sites
- mostly assoc w/ RA, sensitivity equivalent to RF
- greater specificity than RF, useful when RF is negative
- may be detected in healthy people yrs b/f onset of RA


What is an ANA?

- autoabs directed at nuclear ags (or contents of cell nucleus)
- ANAs are serologic hallmarks of systemic autoimmune disease
- provide further dx and prognostic data concerning pts who have minimal sxs or who have clinical features of more than 1 autoimmune disease


Use of ANA?

- help establish a dx in a pt w/ clinical features suggestive of an autoimmune or corrective tissue disorder
- to exclude such disorders in pts w/ few or uncertain clinical findings
- to subclassify a pt w/ est dx of an autoimmune or CT disease
- to monitor disease activity (ex: anti ds-DNA ab levels in lupus nephritis)


Positive ANA is seen in what diseases?

- Systemic autoimmune disease
- organ specific immune diseases (hashiomotos, graves, autoimmune hepatitis)
- variety of infections: mono, hep c, HIV, SBE
- normal individuals - false positives are generally low titers and more commonly seen in women and the elderly
- therefore their presence doesn't mandate the presence of illness


Sensitivities of positive ANA for particular autoimmune diseases?

- SLE: 93%
almost all pts w/ SLE have positive ANA, but this test isn't specific for SLE
- mixed CT disease: 93%
- scleroderma: 85%
- drug induced lupus: 100%


What are non-rheumatic conditions causing positive ANA?

- normal individuals: females over males, increasign age, relatives of pts w/ rheumatic disease, pregnancy
- hepatic disease: chronic active hepatitis
- pulm: idiopathic pulm fibrosis
- chronic infections
- malignancies: lymphoma, leukemia, melanoma, solid tumors (ovary, breast, lung, kidney)
- heme disorders: ITP, autoimmune hemolytic anemai
- drug induced
- misc: autoimmune thyroiditis, type 1 DM


ANA abs seen in normal pop?

- ANA 1:40 - almost 32% of normals
- 1:80 - seen in almost 13%
- 1:160 seen in almost 5%
- 1:320 seen in almost 3%
- no set titer that can distinguish b/t those w/ and w/o SLE
- positive ANAs are commonly found in the normal pop
- for higher titers patterns of ANA may be given:
homogenous, speckled, nucleolar, rim but staining patterns aren't specific and not reliable for dx diff diseases


Criteria for classification of SLE?

- malar rash
- discoid rash
- photosensitivity
- oral ulcers
- arthritis
- serositis
- neuro disorders
- renal disorder: proteinuria or Casts
- heme:
HA w/ reticulocytosis or
leukopenia or
lymphocytopenia or
- immunologic disorder:
antiphospholipid ab or
abnormal titer of anti-nDNA or
anti-Sm (smith ag) or
confirmed false + STS (VDRL)
- ANA (abn titer)

- dx is made when any 4 or more of these manifestations are present, either serially or simulateously


When should an ANA be ordered?

- when your pre-test probability for lupus is moderate (should have at least 3/11 criteria b/f ordering ANA)
- not recommened as random screening test
- not useful to dx other conditions but may support clinical dx


Once the ANA is positive, does it serve a purpose?

- no utility in disease monitoring
- there is no need to repeat it
- specific autoab tests possess dx significance in the right clincal setting


Diff types of ANAs?

- defined by their target ag
- including ds-DNA
- individual nuclear histones
- RNA protein complexes
- some of these abs are relatively specific for a particular disease or for specific clincal manifestations in pts w/ SLE


Use of Anti-dsDNA?

- specific for SLE (60-70%)
- single stranded nonspecific
- farr assay preferable to ELISA
- may fluctuate w/ disease activity (may use to monitor disease)


Use of Anti-Sm?

- highly speciifc for SLE (but not sensitive)


Use of ACA?

- anti-centromere ab (ACA): assoc w/ CREST, and scleroderma


Use of anti-topoisomerase I (Scl-70)?

- assoc w/ diffuse scleroderma


Use of Anti-Ro (SS-A) and La (SS-B)?

- assoc w/ sjogrens
- can be seen in SLE
- may be assoc w/ neonatal heart block in babies of mothers w/ this ab


Use of Anti-U1 snRNP?

- part of criteria for mixed CT disease (MCTD)
- may be seen in other systemic rheumatic diseases


Use of Anti-Jo-1 (anti-histydl-tRNA synthestase)?

- specific for myositis assoc w/ interstitial lung disease
- raynauds


General Utility of ANA?

- not recommended as a screening test
- greatest utility for dx of lupus w/ moderate pre-test probability


What are serum complements? Levels assoc w/ certain rheum diseases?

- not an ab test, but very useful for monitoring disease activity in SLE

low C3 and C4:
-reflect consumption of complement
-demonstrates active SLE
-usually caused by presence of immune complexes in SLE
- seen in some forms of vasculitis


What are Antineutrophil cytoplasmic abs (ANCA)?

- group of abs mainly of IgG type directed against Ags in cytoplasm of neutrophil granulocytes and monocytes
- seen on immunofluoresscence as:
perinuclear staining: P-ANCA
cytoplasmic staining: C-ANCA


ANCA is most strongly assoc w/ what?

- vasculitis
- c-ANCA (PR3): wegner's granulomatosis microscopic polyangiitis
- p-ANCA (MPO): churg-strauss vasculitis


Utility of ANCA?

- ANCA alone isn't dx for vasculitis
- if not ANCA positive - consider dx other than vasculitis


What is HLA-B27? Normal frequency?

- class I MHC product
- alpha chain
- beta-2 microglobulin
- normal frequency:
caucasians 6-10%
african americans 4%
native americans 13%


HLA-B27 syndromes?

- ankylosing spondylitis: over 90%
- reactive arthritis (Reiter's syndrome): over 80%
- enteropathic spondylitis: 75%
- psoriatic spondylitis: 50%


Use of HLA-B27?

- sensitivity 95% for pts w/ ankylosing spondylitis
- present in 5-8% general pop
- incidence of disease: 0.5-1.0%
- HLA-B27 of no value in dx typical back pain pt
- not reqd to confirm a clinical and radiologic dx of ankylosing spondylitis


How do you dx Ankylosing spondylitis?

- clinical evidence - inflammatory back pain of insidious onset, worse in morning, better w/ exercise and NSAIDs
- radiographic evidence (looks like bamboo on x-ray - has syndesmophyte formation)
- HLA-B27 positive


Relative CIs, and complications of arthrocentesis?

- relative CIs:
overlying skin infections
bleeding diathesis
- complications:
cartilage injury
vasovagal episode


Studies from an arthrocentesis?

- appearance: color, turbidity, viscosity, quantity
- cell counts: leukocyte, erythrocyte, diff cell counts, morphologic study
- culture: aerobic, anaerobic
- protein
- glucose
- mucin clot

special studies:
- RF
- complement
- enzymes
- exam for crystals
- immunoglobulins


Normal levels of uric acid? Critical value?

- by-product of purine (adenine, guanin) catabolism:
men 4-8.5 mg/dL
women 2.7-7.3 mg/dL
critical value: greater than 12.0 mg/dL


2 mechanisms of hyperuricemia?

increased production:
- dietary purines (Meat, yeast/beer, beans)
- endogenous purine synthesis (cancers)
- tissue nucleic acid breakdown (chemo, hemolysis)

decreased excetion (75% renal):
- renal failure
- inhibition of tubular urate secretion (competitive anion excess: keto-/lactic acidosis)
- enhanced tubular rate reabsorption (diuretics, insulin resistance, dehydration)


Drugs that effect uric acid levels?

increased by:
-low dose ASA
- caffeine
- vitamin C

decreased by:
- high dose ASA
- estrogens
- corticosteroids


What is the clinical significance of elevated uric acid?

- gout
- asx hyperuricemia: occurence 10% of adult men
- renal impairment
- toxemia of pregnancy (increased catabolism of purines = increased uric acid)
- conditions assoc w/ increased production


What is gout?

- jt pain w/ swelling and erythema
- deposition of sodium urate crystals in jts and tissues: synovial fluid analysis shows neg birefringent needle-shaped crystals
- repeated attacks lead to destruction of tissues and severe arthritic like malformations
- uric acid can be normal in 30% of acute gout attacks


What is CREST syndrome? What tests can be used to help dx this?

- C: calcinosis
- R: raynauds
- E: esophageal dysmotility
- S: sclerodactyly
- T: telangiectasia

- ANA: 70-90% positive
- anti-centromere AB:
70-85% sensitivity
very specific for CREST syndrome


What is Systemic sclerosis (scleroderma)? Tests used to help dx?

- characterized by fxnl and structural abnormalities of small blood vessels, fibrosis of skin and organs, and autoabs
- eosinophilia: 100%
- ANA: 70-90%:
anti-Scl70: 30-70%
nucleolar: 40-70%
- RF: 30%


What is Sjogren's syndrome? Tests used to help dx?

- characterized by diminished lacrimal and salivary gland secretion (sicca syndrome). Pt presents w/ fatigue, dry eyes and mouth
- Anti-Ro (SS-A): 90%
- Anti-La (SS-B): 60%


What are MCTD? Tests used to help dx?

- is a syndrome of overlapping disease manifestations w/ features of: RA, SLE, scleroderma, and polymyositis
- low titer ANA
- nuclear RNP abs: over 95%


What are myositis disorders? Tests?

- dermatomyositis:
inflammatory myopathy w/ cutaneous lesions, muscle pain and weakness
- ANA screening: 40-60% positive
- Anti-PM-Scl: 10%
- increased CPK/Aldolase enzymes
Polymyositis: characterized by progressive muscle pain and weakness
ANA screening 40-60%
anti-PM-Scl: 50%


Are serologic tests for rheum diseases dx?

- no supportive, not dx