DQ typing in Down Syndrome- a standard of care? - Peter Gillett Consultant Gastroenterologist RHSC Edinburgh DSWC Glasgow July 2018 - World Down ...
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DQ typing in Down Syndrome- a
standard of care?
Peter Gillett
Consultant Gastroenterologist
RHSC Edinburgh
DSWC Glasgow July 2018
Declaration • Guideline member, erstwhile pariah ! • NICE NG 20 and NICE QS • BSPGHAN coeliac interest group • ESPGHAN guideline revision group • Coeliac UK HAC member • Scottish Govt MOP coeliac co-lead
Its been a fantastic year, some
momentous events….
The coeliac triad?
• Genes – not the whole story
• Gluten – sequences are ‘key’
• Trigger
– Many postulated
– No universal trigger
– Some studies fail to show significant increase in
infections
– Importance of the microbiome* and environmentMyths busted • Age at gluten introduction not key – the usual time • Breastfeeding during gluten introduction is not protective • Caesarian section is not a risk for subsequent CD • Highest risk for developing CD in Prevent CD study is being female
Guideline
ESPGHAN pre-1990,1990 – 2012 • Three biopsy schedule….. • Serology, biopsy and follow up – Anti-gliadin – Anti-EmA (1992, Chorzelski) – anti tTG (1997, Schuppan) • Capsule succeeded by endoscopic biopsy – D2 and then D1 as standard in addition • All was good with the world……
ESPGHAN / BSPGHAN 2012 - 13
ESPGHAN 2012
BSPGHAN/Coeliac UK guidelines for the diagnosis and management of coeliac disease in children
BSPGHAN/Coeliac UK guidelines for the diagnosis and
management of coeliac disease in children
Murch S et al. Arch Dis Child 2013;98:806-811NICE NG20
Down syndrome – ‘offer testing’
AOECS initiative 2018
CD-The NASPGHAN experience
Coeliac disease….its everywhere ?
Mostly !Epidemiology in the UK
Importance of genetics
HLA DQ2/8 & GLIADIN SEQ.
Other genes than HLA?
Loads !
Importance of other AI
conditions – shared genetics !SCREENING? Genetic testing for coeliac susceptibility genes in children with Type 1 Diabetes Mellitus DQ TYPING IN ‘AT RISK’ GROUPS IN PRACTICE
Type I diabetes
Is HLA cost effective? Probably
st
not in 1 degree relatives
either…The autoimmune connection
? ???????
So who is it pretty helpful for? It’s Down Syndrome isn’t it?
How is DQ typing actually viewed
by families?
Pretty well actually, but
understanding not perfect !Other issues….
Marketing direct to patients and
families increasing?Good Information out there?
Specifics in DS – the coeliac disease association
Background • Early 1970’s first published association (Bentley 1975), pt also had retinoblastoma • Many studies confirm association • Gastrointestinal problems common • Non-specific presentation • Long-term issues • Viability of asymptmatic screening vs expectant watching
Long term issues?
Why screen asymptomatics?
Cancers?Bone health? Associated with DS but no specific proven link
Screening • Why screen? • Patients at identified increased risk • Parents / patient willing and understanding • Accurate and cost effective • Easy for the patient • Treatment acceptable and effective • Prevents long-term issues* • Know your own population prevalence
Screening studies • At least 30 studies…. • Failla P 1996 JPGN 7/57 (12.2%) • Carlsson A 1998 Peds 8/43 (18.6%) • Book L 2000 Am J Med genet 10/97 (10.3%) • Hill I 2000 J Peds 2/10 (20%) • Carnicer J 2001 Eur J Gastr Hep 18/284 (6.3%) • Cassandra G 2000 J Peds 11/137 (8%) • Bonamico M 2001 JPGN 55/1202 (4.6%)
Notable studies
Not always diarrhoea!
Presenting characteristics
60 Five most common presenting symptoms
54.9
50 All diagnosed through
Percentage of new cases
active screening
40 23.1% were actively
31.9 31.9 screened overall for CD
29.7
30 Predominantly due to
20.9 associated type 1 diabetes
20 (67%) or family history
14.3
(29%) of the disease in first
10 degree relatives.
0
Abdominal Failure to Fatigue Diarrhoea Bloating Asymptomatic
Pain thrive
Approximately double
the incidence of
classical cases and
actively screened
cases in the East‘’Screening’’
• History and symptoms: Bonamico 2001
– diarrhoea,vomiting,FTT,anorexia,constipation,
distension higher in CD +
– Hb, Calcium, Iron lower in CD +
– 69% classic presentation
– 11% atypical symptoms
– 20% silent
– 30.9% autoimmune disorders
– Mean delay in diagnosis 3.8 years from onsetScreening – what’s in it for the
individual?
• Case study
• 45 year old female
– iron deficiency anaemia since age 20
– tired, occasional loose stools
– diagnosis menorrhagia as cause
– mother initiated referral
– (actually post menopausal on detailed history)
– Positive biopsyScreening – active case
management ?
• At-risk groups
• Pragmatism
• All about education and awareness
– parents
– public
– Colleagues
• Have a conversation – counselling – almost a
need for informed consentScreening – some unknowns…
• Main concerns??
– asymptomatics
– consequences of positive test (next step)
– risks and benefits
– how often to screen
– problems in other patient groups (parental and
professional attitudes to screening)
– adherence to dietCosts in North America ?
Pitfalls- all tests are not equal !
What’s my message as a biased
gastroenterologist?
At-risk active case finding is key!Recommendations and options • DQ typing on first blood tests OR on a buccal swab if available – that takes out nearly 50% from ongoing concern re coeliac disease* • Positives can be risk stratified DQ 2.5 >8 >2.2 • Cost effectiveness in your health care system is key – may not be covered* • Whole of lifetime risk around 5% - how many tests might an individual have, how many visits to HCPs • Counsel families – ultimately their decision
Recommendations/ comments • No solid evidence for frequency of testing • Pragmatism – if negative first anti TTG and no symptoms, do you just W and W? • When is first anti TTG ? Before school age? • Active case finding- low threshold to test • Personalised medicine – seems right to me to DQ first (not gluten intake dependent) + anti TTG (gluten exposed) • Education of families and HCPs – GPs still uncertainty as to the association
Questions?
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