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Rheumatology > Rheumatology Labs and Diagnostics > Flashcards

Rheumatology Labs and Diagnostics Flashcards

1
Q

Test results must be interpreted based upon statistical parameters of the test performed
4

A
  1. Sensitivity
  2. Specificity
  3. Positive predictive value
  4. Negative predicative value
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2
Q

What is sensitivity?

A

Sensitivity… proportion of patients with positive test who have the disease…. So a negative test will effectively “rule out” disease.

SNOUT

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3
Q

What is specificity?

A

Specificity…proportion of patients with negative test who do not have the disease….. So a positive test will effectively “rule in” a disease.

SPIN

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4
Q

How do I screen for

AUTOIMMUNE DISEASE?

A

-Primarily by history and physical examination

Increase your “pretest probability” by asking questions that support the diagnosis of inflammatory arthropathy or systemic rheumatic disease

Look for clues on physical examination

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5
Q

When to order serologic tests
You should have a compelling reason to
order rheumatologic evaluation tests? 3

A
  1. Assist in confirming a specific diagnosis (high index of clinical suspicion)
  2. Formulate appropriate management
  3. Evaluate/monitor disease activity
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6
Q

Acute Phase Reactants
1. Proteins synthesized by the liver and induced by? 2

  1. What does it parallel?
  2. Purpose? (not for?)
  3. Examples? 4
A
    • Inflammation…. infections, autoimmune disorders, neoplasms
    • Tissue injury/necrosis….trauma, infarction
  2. Parallels chronic inflammation, goes up and down with inflammation
  3. Monitors disease activity
    NOT DIAGNOSTIC
  4. Examples:
    - Coagulation proteins (I, II) fibrinogen levels inc, platelets inc
    - C-reactive protein
    - Complement components (C3, C4, B)
    - Many others: Fibronectin, Transport proteins (Hp, Transferrin, Ceruloplasmin)
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7
Q

Erythrocyte Sedimentation Rate (ESR)

A

The distance at which erythrocytes have settled in a vertical column of anticoagulated blood in an hour (mm/hr).

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8
Q

Erythrocyte Sedimentation rate
Measures what?
2

A
  1. RBC repel one another due to electrostatic forces (negatively charged).
  2. Therefore, they settle in the tube at a certain rate
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9
Q

Inflammatory state: Increased ESR: What is happening on a cellular level?
2

A
  1. Positively charged acute phase proteins neutralize negative charges and allow RBC to aggregate
  2. Now RBC fall at a different rate, and a further distance
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10
Q
  1. The ESR is an indirect measurement of what?
  2. Influenced by the what? 3 (i.e. ESR is increased in anemia)
  3. As a patient’s condition changes the ESR changes at what rate?
A
  1. serum APR concentrations, particularly fibrinogen.
    • size,
    • shape
    • number of RBC’s
  3. relatively slowly
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11
Q

ESR values increase with 1.____and are slightly higher among 2.__________.

As a result, any single set of normal values will not be valid for the population at large.

  1. Both ESR and CRP can be elevated in _______….
  2. this is due at least in part to _____ secretion by adipose tissue
A
  1. age
  2. women than men
  3. obesity
  4. IL-6
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12
Q 
ESR
Normal Values 
1. Male?
2. Female?
3. Children?
  1. Increased by what?
  2. What can affect these levels?
A

Normal Values

  1. Male less than 17 mm/hr
  2. Female less than 25mm/hr
  3. Children less than 10mm/hr
  4. Increased by
    - Acute phase reactants
    - Paraproteins
    - Anemia (fewer cells, less repellent forces)
  5. ALSO
    Age, gender, pregnancy, diabetes, renal failure, malignancy, tissue damage (MI, CVA)
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13
Q

How can we correct ESR for age:

For men and women?

A

For Men
Upper limit of normal of ESR = Age/2

For Women
Upper limit of normal of ESR = (Age + 10)/2

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14
Q
  1. Elevated ESR remains an important diagnostic criterion for two rheumatic conditions

What are they and what levels indicate this? 2

A

Polymyalgia Rheumatica… ESR >40 mm/hr*

Giant Cell Arteritis… ESR >90mm/hr*

*typical value

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15
Q

ESR: Limited utility for differentiating inflammatory joint disease from noninflammatory joint disease…nondiagnostic

Not required for diagnosis of RA
Good history and physical far more significant than ESR in establishing the diagnosis, but ESR can be helpful in what?

A

monitoring disease activity.

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16
Q
  1. What is C-Reactive Protein?
  2. Produced in response to what? (specifically? 2)
  3. Purpose of the CRP?
  4. Acute increase within what? Peaks when?
  5. What are the two types?
A
  1. Acute phase protein produced by the liver
  2. Produced in response to inflammation: ‏
    - Infections
    - Long-term chronic inflammatory illness
    • Enhances complement binding and phagocytosis
    • Acute increase within 6 hours; peaks at 48 hours
  4. Two types of test
    - Standard CRP test (CRP)
    - High-sensitivity CRP (hs-CRP)
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17
Q 
CRP
Direct measure of acute phase reactants
1. Compare sensitivity to ESR?
2. Responds how compared to ESR?
3. Downside? 2
A
  1. Less sensitive than ESR to irrelevant factors (age, gender, anemia)
  2. Responds more quickly
    • More expensive, may not be available
    • Don’t always know how to interpret
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18
Q

Normal adult values for CRP:

  1. Normal?
  2. Low-grade inflammation?
  3. Systemic inflammation?

Children:

  1. Newborn?
  2. Infant?
  3. Pre-pubescent child?
A 
Normal values:
ADULTS
1. Normal: less than 1 mg/L
2. Low-grade inflammation: 1-10 mg/L
3. Systemic inflammation: >10mg/L

CHILDREN

  1. Newborn:less than 15 mg/L
  2. Infant: less than 10 mg/L
  3. Pre-pubescent child: less than 8 mg/L
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19
Q

Problems with ESR and CRP? 3

A

ESR,CRP

  1. Nonspecific indicators of inflammation
  2. Not useful as screening tests for rheumatic diseases
  3. Cannot differentiate one disease from another
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20
Q

What is rheumatoid factor?

A

An AUTO ANTIBODY directed against Fc portion of IgG

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21
Q

RF sensitivity?

A

Sensitivity… 80% in patients with RA

-Sensitivity is the proportion of patients with positive test who have the disease

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22
Q

RF Specificity?

A

Specificity ranges from 80-90%

-Specificity… proportion of patients with negative test who do not have the disease

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23
Q

Sensitivity 80% in patients with RA
Specificity ranges from 80-90%

Prevalence of RA is 0.5-3%
So what does this indicate?

A

So, lots of positive RF are

false positives

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24
Q

Other conditions causing positive Rheumatoid Factor

7

A
  1. SLE
  2. Sclerodema
  3. Sjogren syndrome
  4. Cryoglobulinemia
  5. Infections
  6. Pulmonary diseases (sarcoidosis)
  7. Malignancy
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25
Q

Infection causes of positive RF?

6

A
  1. Hepatitis,
  2. TB,
  3. SBE,
  4. Syphilis,
  5. parasitic disease,
  6. viral illnesses (mononucleosis)
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26
Q

Thus, RF is not diagnostic for RA on its own

-Testing is most useful when there is a what level of suspicion for RA?

A

moderate level

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27
Q

Up to 30% of patients with RA are RF negative early in the disease…

Thus, what counts the most!?

A

clinical impression

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28
Q

Rheumatoid Factor

Normal Value?

A

Normal Value:
Measured as a titer
less than 1:80 is negative

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29
Q

2010 ACR/EULAR classification criteria of RA- Need a total score of at least 6
4

A
  1. Number and site of involved joints (synovitis)
  2. Serological abnormality (rheumatoid factor or anti-ccp antibody)
  3. Elevated acute phase response (ESR or CRP) above the ULN = 1 point
  4. Symptom duration at least six weeks = 1 point
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30
Q
  1. What are the points allotted for the number of joints involved?
    4
  2. Serological abnormality (rheumatoid factor or anti-ccp antibody). Describe the point system for this? 2
A
    • 2 to 10 large joints = 1 point
    • 1 to 3 small joints = 2 points
    • 4 to 10 small joints = 3 points
    • > 10 joints = 5 points
    • Low positive (above ULN) = 2 points
    • High positive (> three times the ULN) = 3 points
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31
Q

In patients with established RA:
1. RF correlates with what? 2

  1. Once test is positive there is no value in re-testing. Why?
A
    • severe articular disease and
    • extra-articular manifestations
  2. RF does not change with disease activity
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32
Q

Key Concepts…more rheum take home
1. Rheumatoid factor is not diagnostic for what?

  1. The test’s utility is greatest when there is what?
A
  1. rheumatoid arthritis

2. a moderate pre-test probability of disease

33
Q

Anti-CCP (citrulline antibody, CCP antibodies)

  1. What is it?
  2. Mostly associated with what?
  3. Useful when? Compare it to RF?
  4. May be detected in healthy people when?
A
  1. Antibody directed against “citrullinated” peptide residues present within inflammatory sites
  2. Mostly associated with RA, sensitivity equivalent to RF
  3. Greater specificity than RF, useful when RF is negative
  4. May be detected in healthy people years before onset of RA
34
Q
  1. What are Anti-nuclear Antibodies (ANA)?
  2. ANAs are serologic hallmarks of what?
  3. Provide further diagnostic and prognostic data concerning patients who have what? 2
A
  1. Autoantibodies directed at nuclear antigens (or contents of cell nucleus).

2, ANAs are serologic hallmarks of systemic autoimmune disease.

    • minimal symptoms or
    • who have clinical features of more than 1 autoimmune disease.
35
Q

The usefulness of testing for ANAs is in the following clinical settings:
4

A
  1. To help establish a diagnosis in a patient with clinical features suggestive of an autoimmune or connective tissue disorder
  2. To exclude such disorders in patients with few or uncertain clinical findings
  3. To subclassify a patient with an established diagnosis of an autoimmune or connective tissue disease
  4. To monitor disease activity (eg, anti-double stranded DNA antibody levels in lupus nephritis)
36
Q

Positive ANA
Seen with:
4

A
  1. Systemic autoimmune disease
  2. Organ-specific immune diseases (Hashimoto’s thyroiditis, Graves’ disease, Autoimmune hepatitis)
  3. Variety of infections (mono, hep c, HIV, SBE)
  4. Normal individuals—false positives are generally low titers and more commonly seen in women and the elderly
37
Q

The sensitivity of a positive ANA for a particular autoimmune disease can vary widely:
In order of the most sensitive, name the disorders in which an ANA will test positive.
10

A
  1. Drug-induced lupus —100%
  2. SLE — 93%
  3. Mixed connective tissue disease — 93%
  4. Scleroderma — 85%
  5. Pauciarticular juvenile chronic arthritis — 71%
  6. Polymyositis/dermatomyositis — 61%
  7. Sjögren’s syndrome — 48%
  8. Rheumatoid arthritis — 41%
  9. Rheumatoid vasculitis — 33%
  10. Discoid lupus — 15%
38
Q

Describe how the ANA is related to SLE dx?

A

Almost all patients with SLE have positive ANA

-The ANA test is not specific for SLE

39
Q

Non-rheumatic conditions causing positive ANA

9

A
  1. Normal individuals:
  2. Hepatic diseases:
  3. Pulmonary diseases: idiopathic pulmonary fibrosis
  4. Chronic infections
  5. Malignancies:
  6. Hematologic disorders:
  7. Drug- induced
  8. autoimmune thyroiditis,
  9. type 1 diabetes mellitus
40
Q
  1. Causes of pos ANA in Normal individuals? 4
  2. Causes in hepatic dz?
  3. Which malignancies might cause this? 4
  4. Heme disorders? 2
A
    • females > males,
    • increasing age,
    • relatives of patients with rheumatic disease,
    • pregnancy
  2. eg. chronic active hepatitis
    • lymphoma,
    • leukemia,
    • melanoma,
    • solid tumors (ovary, breast, lung, kidney)
    • idiopathic thrombocytopenic purpura,
    • autoimmune hemolytic anemia
41
Q
  1. ANA ____ -Seen in almost 32% of normals
  2. ANA _____ Seen in almost 13%
  3. ANA ____ Seen in almost 5%
  4. ANA _____ Seen in almost 3%
  5. There is no set titer that can distinguish between who?
  6. Positive ANAs are commonly found in the what?
A
  1. 1:40
  2. 1:80
  3. 1:160
  4. 1:320
  5. those with and without SLE
  6. normal population
42
Q

For higher titres, patterns of ANA may be given: Such as? 4

Describe the reliability for staining patterns?

A
  1. Homogeneous
  2. Rim
  3. Speckled
  4. Nucleolar

Staining patterns are not specific and not reliable for diagnosing different diseases

43
Q

Criteria for Classification of SLE

11

A
  1. Malar rash
  2. Discoid rash
  3. Photosensitivity
  4. Oral ulcers
  5. Arthritis
  6. Serositis
  7. Neurologic disorder
  8. Renal disorder
  9. Hematologic disorder
  10. Immunologic disorder
    • Antinuclear antibody (abn titer)
44
Q
  1. What renal disorders would suggest SLE? 2
  2. What heme disorders would suggest SLE? 4
  3. What Immunological disorders would suggest SLE? 4
A
  1. Renal disorder
    - Proteinuria OR
    - Casts
  2. Hematologic disorder
    - HA w/reticulocytosis OR
    - Leukopenia OR
    - Lymphocytopenia OR
    - Thrombocytopenia
  3. Immunologic disorder
    - Antiphospholipid antibody OR
    - Abnormal titer of anti-nDNA OR
    - Anti-Sm (Smith antigen) OR
    - Confirmed false + STS (VDRL)
45
Q

So, when should I order an ANA?

A
  1. When your pre-test probability for lupus is moderate (should have at least 3 of the 11 criteria before ordering ANA)

Not recommended as a random screening test

Not useful to diagnose other conditions but may support a clinical diagnosis

46
Q

Can ANA be used to monitor the progress of SLE?

A

ANA has no utility for disease monitoring

47
Q

ANA Profile- Specific Autoantibody Tests: The different types of ANAs are defined by their target antigen? 3

Some of these antibodies are relatively specific for a particular disease or for specific clinical manifestations in patients with SLE.

A
  1. including double stranded DNA
  2. individual nuclear histones
  3. RNA-protein complexes
48
Q

ANA Profile- Specific Autoantibody Tests

  1. Anti-dsDNA specific for what?
  2. What kind of DNA?
  3. What type of preferred assay?
  4. May flucuate with what?
  5. Anti-Sm (Smith antigen) is highly specific for?
A

Anti-dsDNA

  1. Specific for SLE (60-70%)
  2. Single stranded DNA nonspecific
  3. Farr assay preferable to ELISA
  4. May fluctuate with disease activity
  5. Anti-Sm (Smith antigen)
    Highly specific for SLE (but not sensitive)
49
Q

ANA Profile- Specific Autoantibody Tests
1. Anti-centromere antibody (ACA) associated with what? 2

  1. Anti-topoisomerase I (Scl-70) with what?
A
  1. Anti-centromere antibody (ACA)
    - Associated with CREST,
    - and scleroderma
  2. Anti-topoisomerase I (Scl-70)
    Associated with diffuse scleroderma
50
Q

ANA Profile- Specific Autoantibody Tests

  1. Anti-Ro (SS-A) and La (SS-B) associated with?
  2. Can be seen in?
  3. May be associated with what in babies of mothers with this antibody?
A
  1. Associated with Sjogren’s
  2. Can be seen in SLE
  3. neonatal heart block
51
Q

ANA Profile- Specific Autoantibody Tests

  1. Associated with?
  2. Part of criteria for what?
  3. May be seen in?
A

Anti-U1 snRNP

  1. Nonspecific
  2. Part of criteria for mixed connective tissue disease (MCTD)
  3. May be seen in other systemic rheumatic diseases
52
Q

ANA Profile- Specific Autoantibody Tests
Anti-Jo-1 (anti-histidyl-tRNA synthestase):
1. Specific for what?
2. Associated with what also?

A
  1. Specific for myositis associated with interstitial lung disease
  2. Raynaud’s
53
Q

ANA
Not recommended as a screening test
Greatest utility for diagnosis of what?

A

lupus with moderate pre-test probability

54
Q

Serum complements

Not an antibody test, but useful for what?

A

monitoring disease activity in SLE

55
Q

What would Low C3, C4 indicate?

4

A
  1. Reflect consumption of complement
  2. Demonstrates active SLE
  3. Usually caused by presence of immune complexes in SLE
  4. Seen in some forms of vasculitis
56
Q

Antineutrophil Cytoplasmic Antibodies (ANCA)
1. What are they?

  1. Seen on immunofluorescence as? 2
A
  1. Group of autoantibodies mainly of the IgG type directed against antigens in the cytoplasm of neutrophil granulocytes and monocytes
  2. Seen on immunofluorescence as
    - Perinuclear staining - P-ANCA
    - Cytoplasmic staining -C-ANCA
57
Q
  1. ANCA most strongly associated with What?
  2. c-ANCA (PR3)→ indicates? 2
  3. p-ANCA (MPO)→ indicates?
A
  1. vasculitis
    • Wegener’s granulomatosis
    • Microscopic polyangiitis
  3. Churg-Strauss vasculitis
58
Q

ANCA
ANCA alone is not diagnostic for vasculitis
If not ANCA positive, consider what?

A

diagnosis other than vasculitis

59
Q

Human Leukocyte Antigen (HLA-B27)
1. Class I MHC product: What is it made of? 2

  1. Normal frequency:
    - Caucasians?
    - African americans?
    - Native americans?
  2. HLA-B27 Syndromes? 4
    (what is the most related?)
A
  1. Class I MHC product
    - Alpha chain
    - Beta-2-microglobulin
  2. Normal frequency
    - Caucasians 6-10%
    - African Americans 4%
    - Native Americans 13%
  3. HLA-B27 Syndromes
    - Ankylosing spondylitis >90%
    - Reactive arthritis (Reiter’s syndrome) >80%
    - Enteropathic spondylitis 75%
    - Psoriatic spondylitis 50%
60
Q

HLA-B27

  1. Sensitivity 95% for patients with what?
    - Present in 5-8% general population
  2. Not required to confirm a what diagnosis of ankylosing spondylitis ?2
A
  1. ankylosing spondylitis
    • clinical and
    • radiologic
61
Q

Ankylosing Spondylitis- Diagnosis
Dx?
5

A
  1. Inflammatory back pain of insidious onset,
  2. worse in the morning,
  3. better with exercise and NSAID’s
  4. Radiographic evidence
  5. HLA-B27 Positive
62
Q

What findings are on XRAY in ankylosing spondylitis? 2

A
  1. Ossification of the annulus fibrosis

2. Bamboo Spine

63
Q

Arthrocentesis…Procedural considerations
1. Relative contraindications? 2

  1. Complications? 4
A
  1. Relative Contraindications
    - Overlying skin infections
    - Bleeding diathesis
  2. Complications
    - Infection
    - Bleeding
    - Cartilage injury
    - Vasovagal episode
64
Q
  1. What is uric acid a by-product of?

What are normal levels in the following:

  1. Newborn?
  2. Child?
  3. Men?
  4. Women?
  5. Critical Value?
A
  1. By-product of purine (adenine, guanine) catabolism
  2. Newborn: 2.0 – 6.2 mg/dL
  3. Child: 2.0 -5.5 mg/dL
  4. Men: 4.0 – 8.5 mg/dL
  5. Women: 2.7 – 7.3 mg/dL
  6. CRITICAL VALUE: >12.0 mg/dL
65
Q

2 Mechanisms of Hyperuricemia

A
  1. Increased production

2. Decreased excretion

66
Q

Uric acid
2 Mechanisms of Hyperuricemia:
1. Increased production? 3

  1. Decreased excretion? 3
A
  1. Increased production
    - Dietary purines (meat, yeast/beer, beans)
    - Endogenous purine synthesis (cancers)
    - Tissue nucleic acid breakdown (chemotherapy, hemolysis)
  2. Decreased excretion (75% renal)
    - Renal failure
    - Inhibition of tubular urate secretion (competitive anion excess: keto-/lactic acidosis)
    - Enhanced tubular rate reabsorption (diuretics, insulin resistance, dehydration)
67
Q

Uric acid
Drug effects on uric acid levels
1. Increased by? 4
2. Descreased by? 3

A
  1. Increased by
    - Low-dose ASA
    - ETOH
    - Caffeine
    - Vitamin C
  2. Decreased by
    - High-dose ASA
    - Estrogens
    - Corticosteroids
68
Q

Elevated Uric Acid- Clinical Significance

5

A
  1. Gout
  2. Asymptomatic hyperuricemia- Occurrence: 10% adult men
  3. Renal impairment
  4. Toxemia of pregnancy (^ catabolism of purines= ^ uric acid)
  5. Conditions associated with increased production
69
Q

Elevated Uric Acid- Clinical significance

GOUT? 3

A
  1. Joint pain with swelling and erythema
  2. Deposition of sodium urate crystals in joints and tissues.
  3. Repeated attacks lead to destruction of tissues and severe arthritic-like malformations.
70
Q
  1. GOUT- Deposition of sodium urate crystals in joints and tissues: Synovial fluid analysis shows what?
  2. Uric acid can be normal in 30% of what?
A
  1. neg birefringent needle-shaped crystals

2. acute gout attacks

71
Q

GOUT- Tests-Diagnostic Imaging?

A

Examine the involved joints

72
Q

CREST Syndrome

Whats involved? 5

A
  1. Calcinosis
  2. Raynaud’s syndrome
  3. Esophageal dysmotility
  4. Sclerodactyly
  5. Telangiectasia
73
Q

CREST ANA positive how often?

Anti-centromere AB

  • how sensitive?
  • How specific?
A
  1. ANA 70-90% positive
  2. Anti-centromere AB
    - 70-85% sensitivity
    - Very specific for CREST syndrome
74
Q 
Systemic Sclerosis (Scleroderma)
1. Characterized by what?
  1. Eosinophilia?
  2. ANA?
  3. Anti-Scl70: ?
  4. Nucleolar: ?
  5. Rheumatoid factor: ?
A
  1. Characterized by functional and structural abnormalities of small blood vessels, fibrosis of skin and organs, and autoantibodies.
  2. 100%
  3. 70-90%
  4. 30-70%
  5. 40-70%
  6. 30%
75
Q

Sjögren’s Syndrome

  1. Characterized by what?
  2. Anti-Ro (SS-A)?
  3. Anti-La (SS-B)?
A
  1. Characterized by diminished lacrimal and salivary gland secretion (sicca syndrome). Patient presents with fatigue, dry eyes and mouth.
  2. Anti-Ro (SS-A):
76
Q

Mixed Connective Tissue Disorders

  1. What is it?
  2. ANA?
  3. What other antibody test?
A
  1. MCTD is a syndrome of overlapping disease manifestations with features of: RA, SLE, scleroderma and polymyositis
  2. Low titer ANA
  3. Nuclear RNP antibodies >95%
77
Q

Myositis Disorders

  1. ANA screening?
  2. What is dermatomyositis?
  3. Which enzymes are elevated?
A
  1. ANA Screening: 40-60% positive
  2. Dermatomyositis
    - Inflammatory myopathy with cutaneous lesions, and muscle pain and weakness
  3. ↑ CPK/Aldolase enzymes
78
Q

Polymyositis

  1. Characterized by what?
  2. What shows up in 50% of cases?
A
  1. progressive muscle pain and weakness.

2. Anti-PM-Scl

Rheumatology (11 decks)

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