Post by kickingfrog on Apr 18, 2012 9:51:17 GMT
So frustrated - negative coeliac blood test result
Posted by Penny
on 17/4/2012
GF board
I've been chasing up the blood test results for my younger son (who is nearly 3) The doctor who requested the test is away, so another doctor has looked at the result and says it is 'unlikely' that he has coeliac disease, but however, that he is anaemic. ....
...I am still convinced my younger son also has coeliac. i feel I have failed him by not feeding him enough gluten to get a positive blood test result. And I don't know what the best next step is. i want him to get a confirmed diagnosis so that he can get the associated medical support (yearly check-ups etc.) and so that he is not tempted to 'cheat' when he is older.
I think I have to do one of the following:
a) Step up the gluten-content of his food for another 2-3 months and then have another blood test.
b) Make him gluten-free now, and in a year or so's time, introduce gluten for 2-3 months and then have a blood test.
c) Ask to have a biopsy which might show the signs of damage even though the blood test isn't convincing.
Does anyone have any useful experience or advice?
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Posted by Gill M on 17/4/2012
Go back and discuss it with the doctor who requested the test.
Try for c as that would be the best outcome, then a, but avoid b if possible, as re-introducing gluten would be difficult.
...
From Coeliac Mum, Daughter & Me on 17/4/2012
The doctor was probably only reading the exact message printed on the lab results.
The marker for TTG antibodies was probably in the 'normal' range and lab literally print on the results "Coeliac Disease Unlikely" if this is the case.
My last bloods tell me it is unlikely I have coeliac disease - of course that is rubbish - what it means is I have been sticking to the diet!
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From Jacqui on 17/4/2012
...this is so frustrating. My daughter is coeliac and like you we had made our kitchen gluten free - bar the odd sandwich and biscuit for the rest of us. after reading up on coeliac I just knew I had it but had 3 negative blood tests - very frustrating. Spoke to my daughters gastro who is very good - he said to really bombard your system with gluten for a few months ie. eat gluten at EVERY meal and any snacks in between then get another blood test. It was not a pleasant experience - I was so ill eating all this gluten. Sure enough another blood test 2 months later - positive - biopsy - positive villi totally flat - gastro said he thought I had been coeliac for many years - i think the same.
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Posted by Charlotte, Oxford on 17/4/2012
The best bet is to request a endoscopy/biopsy asap while he's still eating gluten. CD can only be excluded by this.
Although blood tests are sensitive in picking up most cases of CD, they are not conclusive and certainly not in a) children under 3 and/or b) when there is a high suspicion of the disease because of family history and/or c) when there are any symptoms (which would included unexplained anaemia). Your son has all of these risk factors for 'seronegative CD'.
The biggest factor in all this is family history: siblings have a 30% risk of CD if they have inherited the sames genes. If there are any health concerns, this alone would justify the biopsy at this age. My younger son had a biopsy to exclude CD in similar circumstances (his asymptomatic brother having been diagnosed by family screening).
I have clinical refs for these if you want (seronegative CD, sensitivity of antibody testing in infants, clinical need for biopsy) but it sounds like your doctors should (and probably will) offer the biopsy. Because of the damage done to coeliac children's permanent teeth at this particular age it is not considered a good idea to delay diagnosis....
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A biopsy is still the safest bet but it may be suggested he has genetic testing (haplotyping) done first. This is not very expensive for hospitals – certainly much less than an gastroscopy/endoscopy. A HLA-DQ2 / DQ8 negative result would make CD unlikely though, occasionally they are not as expected - as in my family: only my coeliac mother had classic DQ2 genes: my coeliac son and I have only ‘half’ the CD genes which is unusual. However neither of my non-coeliac son’s genes were the at-risk ones, so in that sense it was useful. They biopsied anyway.
Note other blood tests which might suggest abnormalities in the BSPGHAN guidelines (below). Obviously the iron blood tests have been done. Another test you may be offered (some gastro paeds offer it to young children) is the AgA test. It’s cheap and much less specific but a positive result could indicate CD in this situation. Certainly having both a positive HLA and AgA would increase the need to biopsy but TBH, in your situation, I would argue for it being done anyway because of his age and the likelihood of your putting him on a GF diet anyway making diagnosis later difficult. The most likely reason for having antibody-negative (seronegative) CD is that the disease has not progressed yet. If he does have CD, this would be good news because you would be treating it early.
REFS:
1) Guidelines
www.coeliac.org.uk/healthcare-professionals/paediatrics/diagnosis-of-children
Coeliac UK guidelines [for diagnosis of children]:
“Although most negative results suggest that someone does not have coeliac disease, it is possible to have false negative results. Further investigations should be carried out in patients whose symptoms are strongly suggestive of coeliac disease.”
“Symptoms such as anaemia and short stature are often more common than the typical malabsorption symptoms (1) associated with coeliac disease. It is therefore important that children are carefully monitored to ensure early diagnosis.”
This explains all tests (US) but useful chart NB Distinction in children less than 3 years old.
labtestsonline.org/understanding/analytes/celiac-disease/tab/test
These are best guidelines for children (as the NICE ones are for adults) and incidentally those to which UK clinicians are referred:
www.bspghan.org.uk/document/coeliac/BSPGHANcoeliacguidelinesFINAL.pdf
“Other blood tests to consider: FBC, U and Es, creatinine, LFTs, Total Protein, glucose,
Coagulation (PT), IgA, IgG, IgM, ferritin, folate, B12, thyroid function tests.
If serology negative but clinical suspicion persists, perform endoscopy and duodenal biopsies
(e.g. chronic diarrhoea, faltering growth, IgA deficiency, positive family history) – to identify
seronegative coeliac disease and other mucosal disorders.”
www.ncbi.nlm.nih.gov/pmc/articles/PMC1976505/
BMJ Publishing Group Ltd 2007 Clinical Review
Adult coeliac disease Andrew D Hopper , Sheffield
“…When considering symptomatic individuals with a family history of coeliac disease (first degree relative), even if the serology is negative a referral to a gastroenterologist for HLA typing (with possible duodenal biopsy) may be warranted. This strategy will ensure that the number of cases missed is minimised.”
www.celiac.com/articles/978/1/So-Why-Do-Celiacs-Still-Need-Biopsy-By-William-Dickey-PhD-MD-FACG/Page1.html
So Why Do Celiacs Still Need Biopsy? By William Dickey
… “Biopsies are necessary when blood tests are negative. While endomysial (EmA) and tissue transglutaminase (TTGA) antibodies are detectable in most cases where villous atrophy is present, 5-10% of patients lack these antibodies1. In this situation, where the story is suggestive of celiac, perhaps with a family history or strongly suggestive symptoms, biopsy is the only way to make the diagnosis. Increasingly, physicians recognize that many patients with gluten sensitivity do not have villous atrophy (Grade III of the Marsh classification) of "classic" celiac disease, but have milder abnormalities such as crypt hyperplasia (Marsh II) or an excess of the inflammatory cells called lymphocytes (Marsh I). Patients in these categories are less likely to have positive serology2.”
These Australian guidelines are very clear:
www.coeliac.org.au/content/downloads/Diagnosing%20coeliac%20disease_printable%20format.pdf
“In children under the age of four years the tTG-IgA test is also less reliable. As antibody levels can fluctuate in children, it is suggested the antibody tests be performed on two occasions three months apart.
….While a normal (negative) coeliac antibody result suggests that coeliac disease is unlikely it can miss the diagnosis in up to 20% of cases. Therefore, doctors should consider further investigation
of people who have risk-factors (listed under symptoms) for coeliac disease irrespective of their antibody result.”
www.gesa.org.au/files/editor_upload/File/Professional/Coeliac_Disease4Ed07.pdf
Beware of false negatives due to:
• IgA deficiency (2% of people with coeliac disease, also transient deficiency common in children)
• Gluten-free diet (can be negative tests after >3months on GF diet)
• Children <2 years – EMA/TTG may not be positive
Gastroscopy with small bowel biopsy
A biopsy of the distal duodenum is the only definitive diagnostic test for coeliac disease. Biopsy should be performed if the patient’s screening antibody blood tests are elevated ( tTG IgA or EMA). Anti Gliadin antibodies should be interpreted in the clinical context if tTG is negative. Biopsy should also be performed in at risk groups and/or symptomatic patients with negative serology as false negatives can occur.
www.coeliacresearch.com/education.asp
This part of the Australian/ New Zealand Coeliac website (created by Professor Bob Anderson) NB “False Negatives:
INFANCY: EmA/TTG is not consistently positive below 4 years old”
3) Research:
Increasing numbers at a specialist coeliac clinic: Contribution of serological testing in primary care W. Dickey Altnagelvin Hospital, Londonderry UK July 2005
www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
“… general practitioners should be prepared to refer for duodenal biopsy if the history is suggestive even where serology is negative.”
www.ncbi.nlm.nih.gov/sites/entrez/11346205?dopt=Abstract&holding=f1000,f1000m,isrctn
Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease Dickey et al Scand J Gastroenterol. 2001 May;36(5):511-4.
“As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.”
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9718937&dopt=Abstract
SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality.
Rostami K, et al Hepatogastroenterology, Rijnstate Hospital, Arnhem, The Netherlands
“…Our study suggests that negative predictive value of serology should be interpreted cautiously since coeliacs with partial VA are negative in serology.”
Coeliac Disease: pitfalls in screening Naam : Kamran Rostami Studierichting : Geneeskunde
Onderwijsinstelling : Universiteit van Amsterdam Afstudeerjaar : 1998 Ph.D thesis
“This study reaffirms our previous work indicating that the appearance of antibodies coexists with the appearance of severe villous atrophy and coeliacs with milder mucosal changes have a lower sensitivity for serology.”
www.celiaccenter.org/documents/CD%20Diagnosis,%20American%20Journal%20of%20Medicine%20August%202010.pdf
Celiac Disease Diagnosis: Simple Rules Are Better Than Complicated Algorithms
Carlo Catassi, MD, MPH,a,b Alessio Fasano* MDa
The American Journal of Medicine (2010) 123, 691-693
[*NB Leading US paediatric CD doctor]
ABSTRACT
“…Instead we find clinically useful the shifting to a quantitative approach that can be defined as the “4 out of 5” rule: the diagnosis of celiac disease is confirmed if at least 4 of the following 5 criteria are satisfied: typical symptoms of celiac disease;
positivity of serum celiac disease immunoglobulin, A class autoantibodies at high titer;
human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes; celiac enteropathy at the small bowel biopsy; and response to the gluten-free diet.
● Conversely, so-called seronegative celiac disease is characterized by clinical, genetic, and histological [biopsy results] data indicating celiac disease in a patient lacking serum TTG and EMA antibodies. Seronegative celiac disease is likely to be underestimated due to the tendency to perform small intestinal biopsy only in patients with positive celiac disease serum markers (so called self-fulfilling prophecy).7 A peculiar type of seronegative celiac disease is found in patients that also have IgA deficiency, who usually lack IgA but often show IgG class celiac autoantibodies.
7. Abrams JA, Diamond B, Rotterdam H, et al. Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy. Dig Dis Sci. 2004;49:546-550.
www.ncbi.nlm.nih.gov/pubmed/15185855
Dig Dis Sci. 2004 Apr;49(4):546-50.
“Seronegative celiac disease occurs…Serologic tests, in clinical practice, lack the sensitivity reported in the literature.”
digestive.niddk.nih.gov/ddiseases/pubs/celiactesting/#ft2
National Digestive Diseases Testing for Celiac Disease
“The tTG test has a sensitivity of more than 90 percent, yielding few false negative results”
AGA
Tests for AGA are not sensitive or specific enough for routine use. However, they may be useful for screening children younger than 18 months old in whom tTG and EMA tests may yield false negative results.*
*Green PHR, Cellier C. Medical progress: celiac disease.
The New England Journal of Medicine. 2007;357:1731–1743.
Anti-endomysial antibody negative celiac disease: does additional serological testing help? Dahele A, et al Department of Medical Sciences, University of Edinburgh, Scotland, Dig Dis Sci. 2001 Jan;46(1):214-21. UK.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=11270789
AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.
A paper by Dahele et al presented at the British Society of Gastroenterology annual meeting found that 21% of patients with untreated coeliac disease were anti-endomysial negative. The use of other serological tests failed to detect many of these patients. The authors concluded that the only definitive means of diagnosing coeliac disease is by small intestinal biopsy.
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