Coeliac Disease: an update
(Febraury 2005)
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Coeliac Disease Update.pdf)
Coeliac disease (CD) is an environmentally triggered autoimmune disease, with gliadin (derived from wheat, barley and oats) causing inflammation of the small intestine. CD typically presents with malabsorption featuring weight loss, abdominal distension, diarrhoea and steatorrhoea. Perhaps because of earlier detection with improved blood tests the clinical presentation of CD has changed over recent decades - diarrhoea is a less frequent symptom than ten years ago, and features such as unexplained iron deficiency and osteoporosis are more common. This extension of the clinical spectrum of disease, in concert with improved diagnostic tests, has led to the revision of the prevalence of CD to around 1:100.
CD should be considered in the differential diagnosis of a range of problems (Table 1).
Table 1: Clinical Features of CD
| Typical Symptoms Suggestive of CD | Other Features Reported in CD | Associated Conditions |
|---|
Chronic diarrhoea
Failure-to-thrive
Abdominal distension |
Malabsorptive:
Malabsorptive:Iron-deficiency anaemia
Short stature
Osteopaenia
Recurrent abortions
Hapatic steatosis
Recurrent abdominal pain
Gaseousness Non-Malabsorptive:
Dermatitis herpetiformis
Dental enamel hypoplasia
Ataxia
Unexplained elevation of liver function tests
Recurrent aphthae
Recurrent pericarditis
Polyneuropathy
Epilepsy
Vasculitis
Dilated cardiomyopathy |
Possibly Gluten-Dependent:
IDDM
Autoimmune thyroiditis
Autoimmune hepatitis
Sjogren syndrome, Addison disease
Autoimmune atrophic gastritis
Alopecia Other Associations:
Down syndrome
Turner syndrome
Williams syndrome
Congenital heart defects
IgA deficiency
Myasthenia gravis
Psoriasis
Primary Biliary Cirrhosis |
Serological testing results (sensitivity, specificity, etc.) are traditionally assessed against a "gold-standard" of biopsy-proven CD affecting the duodenum. However, abnormal coeliac serology in association with normal duodenal biopsies may reflect non-gastrointestinal gluten-sensitivity. Table 2 lists other potential causes for such discrepancies.
Table 2: Six Causes of Serological - Histological Discrepancy in CD
- Management of associated immunopathy (eg corticosteroids can normalise gut architecture)1
- Tissue analysis problems (sampling issues; variability in pathologist inspection (eg subtle intra-epithelial lymphocytosis)2
- Self-imposed dietary restriction leading up to time of biopsy3
- Extra-intestinal CD (many dermatitis herpetiformis patients have "normal" / subtly abnormal small bowel biopsy)4,5
- "Pre-Disease" (Latent CD) - not yet evident at gut biopsy level, but will evolve into CD with time6
- True "false-positive" results are unlikely if result > 2 S.D. above mean (\> 50 U/L)
|
Coeliac Disease Testing
As part of its leading role in coeliac disease, HAPS Immunology has completed a two-year multi-centre study of optimal methods for the serodiagnosis of CD. Based upon the results of this study as well as an extensive literature review, we emphasis the following points.
The diagnostic performance of IgA TGA screening was superior to EMA. Samples submitted for measurement of "endomysial antibodies" will be tested for TGA, unless EMA is specifically requested and approved after discussion with HAPS Immunology.
- Dual-isotype testing of TGA IgA + TGA IgG enhanced diagnostic yield for CD. The combined isotype TGA testing approach was superior to either isotype measured in isolation. HAPS Immunology is introducing a combined isotype TGA IgA/IgG for CD screening.
- TGA levels correlate well with dietary compliance with a gluten-free diet, offering similar utility to gliadin antibody measurement. Due to poor specificity, IgG-gliadin antibody testing will no longer be offered routinely, unless by specific request.
- A positive result using our new TGA testing strategy displays a positive likelihood ratio of 8. This means that a positive result will increase the likelihood of disease 8-fold compared to your pre-test level of diagnostic suspicion. The negative likelihood for this test is high, meaning that negative result makes CD less than 5% likely.
- The final arbiter in diagnosing CD is a biopsy of affected tissue (small bowel or skin). Strongly positive TGA results (>50), repeated abnormal serology on two occasions separated by six weeks or persisting strong diagnostic suspicion for CD should prompt biopsy assessment (the "god standard" for CD diagnosis).
In conclusion, when coeliac disease is clinically suspected on the basis of gastrointestinal or systemic features, testing for antibodies to TGA (which will include both IgA and IgG-TGA in our laboratory) offer a sensitive, specific and reliable screening strategy.
About the Authors
This HAPS Communique was written by Dr Glenn Reeves (Clinical Staff Specialist), Prof. Robert Clancy (Director), Dr Theo deMalmanche (Registrar) and Karla Lemmert (Unit Supervisor).
If you have any questions regarding this topic Immunology can be contacted on Telephone: (02) 49214000, Facsimile: (02) 49214400.
References
- Confalonieri F, Pedretti D, Parisio E (1995). "Adult-onset coeliac disease hidden by chronic steroid therapy for skin disease." Am J Med 99(4):439-40.
- Oberhuber G, Granditsch G, Vogelsang H. (1999). "The histopathology of coeliac disease: time for a standardised report scheme for pathologists." Eur J Gastroenterol Hepatol 11(10): 1185-94
- Reeves GE, Burns C, Hall ST, Gleeson M, Lemmert K (2000). "The measurement of IgA and IgG transglutaminase antibodies in coeliac disease: a comparison with current diagnostic methods." Pathology 32(3): 181-5.
- Oxentenko AS, Murray JA. (2003) "Coeliac disease and dermatitis herpetiformis: the spectrum of gluten-sensitive enteropathy." Int J Dermatol 42:586-7.
- Martucci S, Biagi F, Di Sabatino A, Corazza GR, et al. (2002). "Coeliac disease." Dig Liver Dis 34 (S2): S150-3.
- Cerf-Bensussan N, Cellier C, Heyman M, Brousse N, Schmitz J. (2003) "Coeliac disease: an update on facts and questions based on the 10th International Symposium on Coeliac Disease & J Pediatr Gastroenterol Nutr 37(4):412-21.
- References