Coeliac disease
BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1561 (Published 03 March 2014) Cite this as: BMJ 2014;348:g1561
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Till the recent past, there was no cure for coeliac disease but following a strict gluten-free diet can help manage symptoms and promote intestinal healing. Despite adherence to a gluten-free diet, many patients remain symptomatic and still have small intestinal inflammation (1). In this case, nondietary therapies are needed. But recently, in a paper published in Gastroenterology, the authors investigated the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases given orally, to protect patients with coeliac disease from gluten-induced mucosal injury in a phase 2 trial and noted that they are protective.
References:
1: Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP, Kärjä-Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Glutenase ALV003 Attenuates Gluten-Induced Mucosal Injury in Patients With Celiac Disease. Gastroenterology. 2014 Jun;146(7):1649-58. doi: 10.1053/j.gastro.2014.02.031. Epub 2014 Feb 25.
Competing interests: No competing interests
Mooney and colleagues in their clinical review of coeliac disease pose the question 'What if serological testing is negative but the clinical suspicion of coeliac disease is high?' They list other causes of villous atrophy, not due to gluten sensitivity, which may result in coeliac-like symptoms but omit an important cause: infestation with Giardia lamblia. Over three decades I came across half a dozen people, all Caucasian, with profound malabsorption which failed to respond to a gluten-free diet. Duodenal biopsy in all cases showed total villous atrophy. My clever histologist, Peter Steele, at the Countess of Chester Hospital, noticed the parasites sitting on the surface of the mucosa. Resolution of the symptoms after a course of metronidazole was dramatic. Subjects were delighted to be able to stop the gluten-free diet.
The crucial factor in this satisfying diagnosis is a Giardia-aware histologist.
Competing interests: No competing interests
The authors describe atypical presentation of coeliac disease (CD) as a pitfall impeding diagnosis. Recognising this, consensus has classified CD as symptomatic, silent or potential according to symptoms and investigation results (1).
We recently diagnosed CD in a man who presented with severe chronic hypocalcaemia secondary to vitamin D deficiency. Malabsorptive symptoms had developed only after trialling celecoxib at the age of 73. The patient had stopped the drug as a result, but the diarrhoea persisted. He had a family history of CD and screening found other autoimmune conditions. Serum IgA tissue transglutaminase antibodies and duodenal biopsy were positive for CD. He has symptomatically improved on a gluten free diet with vitamin D and calcium supplementation.
This illustrates the phenomenon of potential CD, putatively triggered by the inflammatory effect of the NSAID.
Reference
1. Spectrum of gluten related disorders: consensus on new nomenclature and classification. Sapone et al., BMC Medicine, 2012, 10: 13
Patient consent obtained.
Competing interests: No competing interests
The article is an interesting and informative overview of coeliac disease. However, the discussion related to the necessity of a duodenal biopsy in adults seems comparatively inadequate; especially considering that it is reported that European guidelines provide an algorithm for avoidance of biopsy in children (1).
The formal diagnosis of coeliac disease seems to be an academic endeavour in certain cases. If an adult patient has resolution of symptoms on a gluten-free diet, especially if combined with high serological markers, can this not be enough to recommend continued trial of dietary gluten avoidance? Even if the patient has Irritable Bowel Syndrome with an element of gluten-sensitivity, the treatment will be the same. The insistence on endoscopy seems unnecessary in these cases; both in relation to patients’ perceptions and experience of such an invasive procedure and to the financial costs associated with it. Such line of thought is not unique and other authors have recommended that intestinal biopsy is not mandatory in all cases (2)(3).
Another factor is that of an ethical one. It is well known that a fundamental basis of medicine is ‘primum nil nocere’ (‘first, do no harm’). It therefore seems erroneous to encourage patients to continue with gluten-containing diets whilst awaiting an endoscopy appointment, especially when serological tests can be taken within one or two days. Even more conflicting is prescribing individuals a ‘gluten challenge’ with the explicit aim to create the histological features, but also concomitant symptoms, to aid the diagnosis of a disease for which the treatment may have already had benefit.
There is undoubtedly still a role for endoscopy and biopsy, as well as gluten challenges, but these invasive and potentially harmful regimens can surely be reserved for those with more complicated clinical situations.
Dr Andrew L. Smith
andrew.smith87@doctors.org.uk
(1) Husby S, Koletzko S, Korponay-Szabó IR, et. al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease.́ Journal of Pediatric Gastroenterology and Nutrition 2012:54;1.
(2) Bürgin-Wolff A, Mauro B, Faruk H. Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests. BMC Gastroenterology. 2013 Jan 23;13:19.
(3) Wakim-Fleming J, PagadalaMR, Lemyre MS, et. al. Diagnosis of celiac disease in adults based on serology test results, without small-bowel biopsy. Clinical Gastroentrology and Hepatology. 2013;11(5):511-6.
Competing interests: No competing interests
Our experience in seeking the cause of iron deficiency anaemia in the absence of clinical pointers suggests that considering coeliac disease earlier than has been customary will lead to the correct diagnosis sooner in selected groups. Four out of seven diagnoses in patients under 44 were of coeliac disease and two out of 10 in the group up to 64 years of age. (Ref. Willoughby JMT, Laitner, SM, Audit of the investigation of iron deficiency anaemia in a district general hospital, with sample guidelines for future practice Postgrad. med. Journal 2000; 76: 218-222)
Now that diagnostic blood tests for coeliac disease are available, selection of initial investigations on such a basis would seem even more strongly indicated than it did 14 years ago.
Competing interests: No competing interests
Re: Coeliac disease
Authors said, "Treatment with a lifelong strict gluten-free diet is currently the only treatment of known effectiveness "(1). As we said in our previous reaponse of the same paper - "Recently, in a paper published in Gastroenterology, the authors investigated the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases given orally, to protect patients with coeliac disease from gluten-induced mucosal injury in a phase 2 trial and noted that they are protective(2)".
Here, we would like to add that these recombinant proteases can act on the gluten in vitro also and the gluten will get digested and will become innocuous outside the body (or more precisely the intestines). The recombinant technique can manufacture large amount of enzymes in a short time and at very low cost..
References:
1. BMJ 2014;348:g1561
2. Lähdeaho ML, Kaukinen K, Laurila K, Vuotikka P, Koivurova OP, Kärjä-Lahdensuu T, Marcantonio A, Adelman DC, Mäki M. Glutenase ALV003 Attenuates Gluten-Induced Mucosal Injury in Patients With Celiac Disease. Gastroenterology. 2014 Jun;146(7):1649-58. doi: 10.1053/j.gastro.2014.02.031. Epub 2014 Feb 25.
Competing interests: No competing interests