PEGASUS HEALTHGP SMALL GROUP EDUCATION

DIAGNOSTIC DILEMMAS

Diagnostic Dilemmas

Tests covered in this session:

Faecal calprotectin HLA DQ2/DQ8 Homocysteine BNP Vitamin D (a quick look at data)

Case One

Samantha, 34 year old woman: 6/12 diarrhoea Abdo cramps Occasional PR bleeding No weight loss

What else would you like to know?What are the differential

diagnoses?

Case One – Differential Dx

Irritable Bowel Syndrome Coeliac Disease Inflammatory Bowel Disease Lactose Intolerance Infective Diarrhoea Endometriosis Pelvic Inflammatory Disease Cancer in older patient – Colorectal or

Ovarian

What tests (if any) would you order for Samantha?

Faecal Calprotectin Testing

Pros: Helps rule out inflammatory causes of diarrhoea High negative predictive value

Cons: Can be raised in all causes of GI inflammation

(including irritation from NSAID use) Many false positives occur Also increases with age, inactivity, and obesity

Samantha – 6 Months Later

Sister just diagnosed with coeliac disease

Samantha on gluten free diet last 4/52 with only slight improvement in symptoms

Requesting blood test for coeliac disease

What do you do now?Is HLA gene testing appropriate?

Human Leucocyte Antigens & Coeliac Disease

>99% coeliac patients are HLA DQ2/DQ8 positive HLA testing has >99% negative predictive value

20-30% general population HLA DQ2/DQ8 positive• only 3% of these will develop coeliac disease

HLA genes necessary but not sufficient

for development of coeliac disease

Human Leucocyte Antigens & Coeliac Disease

Entire NZ Population

30% of Caucasian population will test positive for HLA DQ2/8

3% of those with a positive HLA will develop coeliac disease

0.1% of those with negative HLA will develop coeliac disease

Illustration for Patients

What Role Does HLA Typing Play?

Not diagnostic for coeliac disease (high rate false +ve)

Negative test rules out coeliac disease

IgA tTG is first-line test for Dx coeliac disease

If positive, go back on gluten for 4wks then test IgA tTG and total IgA

HLA testing not indicated if family history coeliac disease

(~10% prevalence in 1st degree relatives)

Vitamin D Testing

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21-30

31-40

41-50

51-99

100+

92

50

41

3128

14 149 10

611

4 3 4 2 2 2 1 0 1

7 6 4 6 6

GP count by number of tests(9 month period from July 09 – Mar

10)

Total number tests = 2911Number unique patients = 2780

Number of GPs

Number of tests/GP

Indications for Testing Vitamin D

Atypical osteoporosis

Unexplained raised serum alkaline phosphatase or low calcium or phosphate

Unexplained proximal limb pain in older people

Unexplained bone pain, unusual fractures or other evidence suggesting metabolic bone disease

Malabsorption disorders

Long-term anticonvulsant therapy

High risk for deficiency

Consider supplementation for: Institutionalised or house-bound elderly People who are veiled Very dark skin and little sunlight Infants exclusively breastfed by mothers at

risk of deficiency Cholecalciferol 1.25mg 2 stat then 1

monthly No requirement for prior testing or

monitoring

Case 2 - Homocysteine

Bill, 55yrs, long-term patient, few visits

Recent NSTEMI

Committed to changing his lifestyle to reduce his risk of another “heart attack”

Wants his homocysteine level tested

What do you know about homocysteine?

Hyperhomocysteinaemia

Has been linked to: MI, acute coronary syndrome, recurrent coronary

events Premature coronary heart disease Cardiovascular and total mortality Adverse outcomes after angioplasty Carotid artery stenosis Stroke, recurrent stroke, silent brain infarct Venous thromboembolic disease (PE/DVT)

What factors can cause ↑ homocysteine levels?

Is Knowledge of Homocysteine Level Useful in Improving Outcome?

There is evidence that reducing homocysteine levels is of no benefit

There is no evidence to support screening

Routine homocysteine testing is not justified

So… Would you Test Bill?

No. What would you tell Bill?

Knowing Bill’s homocysteine level will not alter his management or risk

Modification of risk factors such as DM, smoking, hypertension, and

hypercholesterolemia shown to be beneficial

Case 3

John, 73y, 1mth history increasing SOB

NSTEMI 18 mth ago

Mild hypertension, hypercholesterolaemia

On Examination• Temp 37.6, P 88 reg, BP 150/95• HS dual and nil• Chest dull at bases, some coarse creps• Trace pedal oedema

What else do you want to know?What are the differential diagnoses?What investigations would you do?

BNP (Brain Natriuretic Peptide) Secreted in response to ventricular

distension

High negative predictive value useful for ruling out HF

Diagnosing HF is difficult in Primary Care:- Early symptoms often mild and non-

specific- Clinical findings neither specific nor

sensitive- Echo not readily available

Back to John…

BNP = 52 pmol/L What does this mean?

A normal BNP in an untreated patient effectively rules-out heart failure

An intermediate BNP does not rule out heart failure

A high BNP indicates heart failure but does not exclude other chest/heart problems

< 30 Low – HF unlikely (2%)30 – 80 Indeterminate – HF still possible>80 High – HF likely (95%)

Alternative Scenario

What if John’s BNP was 217 pmol/L? (High)

What would this mean?

How would you manage him?

Can you use BNP testing to guide optimal drug treatment of John’s

HF?

When is BNP Useful in General Practice?

High BNP supports diagnosis of HF o but does not exclude other conditions

Low BNP can rule out HF in an untreated patient

May have role in known HF patientso for helping diagnose cause of acute dyspnoea

When is BNP not Useful in General Practice?

No role in screening for asymptomatic LV

dysfunction monitoring well patients who have

HF excluding CHF in those already on

therapy

Not recommended for guiding drug titration in HF patients with obvious clinical

diagnosis of HF

BNP Data

1 to 5 6 to 10 11 to 15

16 to 20

21 to 25

26 to 30

31 to 35

36 to 40

41 to 45

46 to 50

51 to 100

> 1000

20

40

60

80

100

120

140

160

180

200

175

85

57

22 20 169

4 7 38

2

GP count by number of BNP tests(9 month period from July 09 – Mar

10)Total number tests = 4563Number unique patients = 3728

Number of GPs

Number of tests/GP

Summary - Diagnostic Dilemmas

‘Off-schedule’ tests were developed in 2° care - Place in 1° care not yet established

Only test if it will influence management

Most of these tests have significant limitations

Test results may be misleading

Paramount to use clinical judgment

Take Home Messages

Faecal Calprotectin • second line test • may help rule out Inflammatory Bowel Disease

in young patient with chronic diarrhoea

HLA DQ2/DQ8• Not recommended to diagnose Coeliac Disease• 30% of Caucasians express these markers

Vitamin D• Don’t test, just treat

Take Home Messages Cont’d

Homocysteine • Reducing levels does not improve patient

outcomes• No role for testing

BNP• If normal, useful to rule out HF• If high, may support diagnosis of HF• May be raised by other conditions that strain the

heart

Sometimes it is best not to do a test!