1. health and fitness
2. disease

“Vasculitis Screen”
and
“Autoimmune Screen”
Theo de Malmanche
Put this in your search engine:
RCPAmanual
Your lab
• Can put “HAPS” in your search engine
Or ring 14000 and
ask for a chat with
someone who
knows about
(whatever it is)…..
The brief
TERM 2 – PATHOLOGY TESTS: ORDERING AND INTERPRETATION
Should ideally include, but not be limited to, a discussion of the following
points:
1. Local systems for test ordering
2. Rational test ordering, with consideration of:
a. Costs
b. Clinical benefit to the patient
3. Common order sets - what they include and their interpretation
a. Vasculitic/autoimmune screen
b. Coagulopathic screen
c. Haemolysis screen
d. Hepatitis screen
e. Atypical pneumonia serology
4. Basic interpretation of common tests – when to be concerned
a. Full blood count
b. Electrolytes (EUC and CMP)
c. Coagulation profile
d. Liver function tests
1. Local systems for test ordering
• Prof Kellerman also discussing this
Who really cares about the forms?
• Request forms are a form of consultation
• Consequence of incomplete or inaccurate
request forms are traceable
– These forms are required by law to be
retained
• When reviewing results, I am often guided
by the level of detail.
– If you do not care about the patient’s result,
then you must have a low pre-test probability
Who reads the forms?
At least:
1.The blood collector
2.Specimen reception staff
3.Data entry staff
4.Lab scientific staff – to confirm test selection
5.Lab scientific staff – interpretation of result
6.Pathologist when validating results
2. Rational test ordering, with consideration
of:
a. Costs
b. Clinical benefit to the patient
Example of cost to taxpayer of
testing:
(values are 85% MBS, i.e done in
public hospital lab, on inpatients)
Test
Cost
Running total
FBC
$14.50
$14.50
UEC, LFT (5 or more of
66500)
$15.15
$29.65
CRP
$8.30
$37.95
ESR
$3.95
$41.90
ANA
$20.95
$62.85
ANCA (if pos screen)
$51.60
$114.45
Rheumatoid Factor
$9.70
$124.15
CCP
$14.85
$139.00
ENA (if pos)
$44.55
$183.55
C3, C4
$24.80
$208.35
ENA (if neg)
$14.90
Competing pressures
• Cost of bedstay in NSW hospitals ~$500
per day
• A delayed diagnosis can be expensive
– Directly and indirectly
• Every request form is a new venepuncture
– Can it be added on?
– Can it wait until Monday or Tuesday?
• Unnecessary testing – leads to more
testing.
– This may delay discharge
3. Common order sets - what they include
and their interpretation
a. Vasculitic/autoimmune screen
b. Coagulopathic screen*
c. Haemolysis screen*
d. Hepatitis screen
e. Atypical pneumonia serology
* Haematology talk in next term
“Vasculitis Screen”
and
“Autoimmune Screen”
15 min on the tests you should not order
Theo de Malmanche
•
•
•
•
First - the symptoms
Second – signs
Third – the provisional diagnosis
Then Fourth – the test
For immune disorders
1. Systems review eg. head to toe
– What are the symptoms
– Are there features suggesting inflammation without infection?
2.
3.
4.
5.
Is it inflammatory?
Is it organ threatening?
Do we need to biopsy?
Then, which tests might support the provisional
diagnosis?
6. What can we use as a marker of inflammation?
– Number of joints, extent of rash, duration of stiffness, frequency or
duration of episodes
If in doubt… …“Hold Serum”
• A low level / borderline / indeterminate
result of questionable significance will
cause more trouble than it is worth
– eg. B27 pos – now what? ?XR Lspine?
• Serological tests can be added on at a
later date to stored serum
• Tests like B27, DQ2/DQ8, HFE testing are
the same throughout life, no urgency
Vasculitis – what it is (clinically)
• Features include:
– Features of inflammation
– Features of ischaemia
– Associated specific features
Vasculitis – what it is (clinically)
• Often some features of inflammation
without distinct focus
– Eg. Fatigue, myalgia, sweats, weight loss
– May be reflected in inflammatory markers eg.
CRP
• Tissue ischaemia
– Which may or may not lead to organ
dysfunction
Symptoms vary with organ(s)
affected
Redundancy
• “Picking off” blood supply to
some organs will only have
noticeable effect on function
when the “functioning mass” is
sufficiently reduced
– Kidney, lung
• Other organs will be
symptomatic as soon as blood
flow is reduced
– Brain
Collaterals - chronicity
• Collaterals develop if the reduction of
blood flow has been a gradual process
– Tissue ischaemia leads to growth factor
release
– This leads to new blood vessel formation
•
Symptom complexes ischaemia
Skin involvement
– Rash, especially pupurae
•
Cerebral involvement
– CNS dysfunction, can be like a stroke
•
Renal involvement
– Renal failure, an “active sediment”
•
•
Renal failure -> hypertension
Mesenteric involvement
– Pain after eating, bleeding into bowel, gut infarction, scrotal pain
•
Muscle involvement
– Muscle pain and tenderness, cramping
•
•
•
Scalp -> headaches
Tongue and mastoid mm. cramping classic in GCA
Retinal involvement
– Visual loss, usually permanent
•
Heart involvement
– Acute coronary syndrome (occlusion) or angina (stenoses)
•
Peripheral nerve involvement
– Peripheral neuropathy, can be mononeuritis or symmetrical
•
Lung involvement
– Bleeding, nodules, cavitation
Specific features
These are often hard to find
• Detectable vasculitis
– Tenderness and swelling of the vessels
• Esp temporal arteries in GCA, but also carotids and subclavians
– Bruits – but more due to something other than vasculitis
• Eg axillary in GCA
• Granulomatous features in granulomatous vasculitis
– Eg. Granulomatous sinusitis, lung granulomata
• Asthma in Churg-Strauss Syndrome
• Precedent pharyngitis in Henoch-Schonlein Purpurae
Vasculitis – what it is not
• Thrombosis without inflammation
– Thromboembolic, cholesterol, plaque rupture
• Vasculopathy without inflammation
– Atherosclerosis, fibromuscular dysplasia, congophilic
angiopathy, cystic medial dysplasia,
• The above are more common than vasculitis
• Also
• Vasospasm
• Organ dysfunction without vasculitis
– Cerebritis
• These do not improve with immunosuppression
Suggested approach
• Which organs are involved
– Systems review (history)
– General examination
– Urinanalysis
• Severity
– Are any organs threatened?
• Evidence of inflammation?
• Consider confirmation of diagnosis
• If organ threatening – treat with steroids, chase
diagnosis
• If not organ threatening – chase diagnosis
Diagnosis of vasculitis
• Gold standard
– Biopsy showing necrotising vasculitis
• Inflammation with disruption of vascular structures
• Surrogates
– Imaging demonstrating vascular damage
– Evidence of this being inflammatory
– Classic syndrome typical of known vasculitis
– Exclusion of other likely causes
Levels of confidence
• Biopsy with typical findings
• Biopsy with consistent findings
• Conventional angiogram with classic
findings
• CT angiogram with classic findings
• Magnetic resonance angiography
• Nuclear scans
• Clinical syndrome
Standard of proof
Is your diagnosis:
• Beyond reasonable doubt?
• On the balance of probabilities?
• On reasonable suspicion?
• On justifiable grounds?
When the patient has an adverse effect, how
justified was your decision to treat?
• Consider severity (urgency) and confidence
of diagnosis
Treatment approach
• Halt progression / Induce remission
– Steroids
• Consolidate remission
– Steroids and ?cyclophosphamide
• Maintainence (prevent relapse)
– “Steroid sparers” eg. Methotrexate,
azathioprine
Natural history
• Bad (will lead to organ failure +/- death)
– ANCA-associated vasculitides
• Granulomatous vasculitis (nee WG), Churg Strauss Syndrome,
microscopic polyangiitis
– Polyarteritis Nodosa, Temporal arteritis
– Meningococcaemia
– Dengue Haemorrhagic fever
• Not so bad
– Leucocytoclastic vasculitis
• Eg due to medication, viral infection, Sjogren’s Syndrome
– Henoch-Schonlein Purpurae
• Rarely needs therapy
The “vasculitis screen”
• Look for evidence of ischaemia
– Systems review
• Look for evidence of inflammation
– Examination, including UA
• Consider biopsy
– One sample needs to be not fixed (not
formalin)
• Consider supportive evidence
Which have helpful blood tests?
•
•
•
•
•
•
•
•
No
ANCA
ANCA
No
No
No
No
No
• If in doubt, hold serum, or ask someone
• Rubbish in, rubbish out