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)
- 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
- 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:
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?
- Sjogren syndrome
- infections: Hep, TB, SBE, Syphilis, parasitic disease, viral (mono)
- pulm diseases (sarcoidosis)
- 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
- oral ulcers
- neuro disorders
- renal disorder: proteinuria or Casts
HA w/ reticulocytosis 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
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?
- 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:
african americans 4%
native americans 13%
- 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
Studies from an arthrocentesis?
- appearance: color, turbidity, viscosity, quantity
- cell counts: leukocyte, erythrocyte, diff cell counts, morphologic study
- culture: aerobic, anaerobic
- mucin clot
- exam for crystals
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?
- 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?
-low dose ASA
- vitamin C
- high dose ASA
What is the clinical significance of elevated uric acid?
- 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:
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%:
- 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?
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%