Pegasus Health GP Small Group Education Diagnostic Dilemmas

1. Pegasus HealthGP Small Group EducationDiagnostic Dilemmas

2. Diagnostic Dilemmas Tests covered in this session: • Faecal calprotectin • HLA DQ2/DQ8 • Homocysteine • BNP • Vitamin D (a quick look at data)

3. Case One Samantha, 34 year old woman: • 6/12 diarrhoea • Abdocramps • Occasional PR bleeding • No weight loss What else would you like to know? What are the differential diagnoses?

4. 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?

5. 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

6. 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?

7. 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

8. 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 HLAwill develop coeliac disease 0.1% of those with negative HLA will develop coeliac disease

9. Illustration for Patients

10. 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 IgAtTG and total IgA • HLA testing not indicated if family history coeliac disease (~10% prevalence in 1st degree relatives)

11. Vitamin D Testing

12. 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

13. 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

14. 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?

15. 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?

16. 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

17. 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

18. 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?

19. 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

20. 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%)

21. 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?

22. When is BNP Useful in General Practice? • High BNP supports diagnosis of HF • but does not exclude other conditions • Low BNP can rule out HF in an untreated patient • May have role in known HF patients • for helping diagnose cause of acute dyspnoea

23. 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

24. BNP Data

25. 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

26. 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

27. 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!