Scientific letter
Non-responsive coeliac disease: Coeliac crisis vs. refractory coeliac disease with response to corticosteroids
Enfermedad celíaca no respondedora: crisis celíaca vs. enfermedad celíaca refractaria con respuesta a corticoides
Mayra Lindo Ricce
, Beatriz Rodriguez-Batllori Arán, Mirella Jiménez Gómez, Javier P. Gisbert, Cecilio Santander
Corresponding author
Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
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"apellidos" => "Gisbert" ] 4 => array:2 [ "nombre" => "Cecilio" "apellidos" => "Santander" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad celíaca no respondedora: crisis celíaca vs. enfermedad celíaca refractaria con respuesta a corticoides" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Coeliac disease (CD) is an immune-mediated enteropathy, triggered by the ingestion of gluten in genetically predisposed individuals, with various gastrointestinal and systemic manifestations.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Most patients respond to a gluten-free diet (GFD), but there is a percentage of patients with non-responsive CD, with the main cause being poor adherence to a GFD.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> With lesser frequency, the lack of response is due to refractory coeliac disease (RCD).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Coeliac crisis (CC) is a rare and potentially fatal complication of CD.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 63-year-old woman with a history of hypertension and hyperthyroidism, undergoing treatment with carbimazole and torasemide. She was admitted to hospital for chronic diarrhoea with symptoms of severe malnutrition and an organic psychotic mania episode secondary to CD (diagnosis confirmed with intestinal biopsy consistent with Marsh 3a and positive tissue transglutaminase-IgA antibodies [tTG-IgA]: 45<span class="elsevierStyleHsp" style=""></span>U/ml [normal value: <20<span class="elsevierStyleHsp" style=""></span>U/ml]), which responded clinically and analytically to a GFD (tTG: 2<span class="elsevierStyleHsp" style=""></span>U/ml at 2 months after the episode). At 3 months from diagnosis, she was readmitted for disassociated psychosis and severe diarrhoea of rapid progression, with protein-calorie malnutrition, electrolyte imbalances and vitamin deficiencies, despite good adherence to the GFD. Intestinal infections were ruled out (negative faecal cultures and negative viral, bacterial and mycobacterial cultures in intestinal tissue samples). The tTG were determined at admission. They were positive at low titers (25<span class="elsevierStyleHsp" style=""></span>U/ml) and became negative on the fifth day of admission after GFD (9<span class="elsevierStyleHsp" style=""></span>U/ml). The genetic test was positive (HLA-DQ2) and the intestinal biopsies showed mucosal atrophy (Marsh 3b in the jejunum and Marsh 3c in the duodenum). During her stay, the patient required blood concentrate transfusions, electrolyte replenishment and parenteral nutrition. After one month without responding to the GFD, the patient developed pneumonia with severe respiratory failure, which was treated with levofloxacin and linezolid, as well as intravenous corticosteroids (methylprednisolone 1<span class="elsevierStyleHsp" style=""></span>mg/kg), after which she had an excellent response both in the respiratory and digestive symptoms. At discharge, the corticosteroid treatment regimen was tapered off with good response. After one year of follow-up and good adherence to the GFD, the patient was asymptomatic with negative tTG (2<span class="elsevierStyleHsp" style=""></span>U/ml).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Non-responsive CD is defined as CD that does not respond after 6–12 months on a GFD.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Up to 10–20% of patients with CD develop non-responsive CD,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> with non-adherence to the GFD being the main cause of the lack of response.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">tTG values tend to turn negative after a variable amount of time on a GFD. However, they can remain positive in up to 20-30% of patients with RCD despite good adherence to the GFD.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,6</span></a> In our case, the patient had positive tTG values at low titers at admission which could be a false positive or contamination with trace amounts of gluten. The rapid negativisation of said values is notable, given that the antibody levels usually decrease gradually after removing gluten from the diet (half-life of 6–8 weeks).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> These disparate levels in a short period of time caused confusion in the diagnosis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Given the suspicion of contamination with trace amounts of gluten, the differential diagnosis of CC could be suggested. CC is a fulminant presentation of CD, with very few cases having been reported in adult patients. It is defined as an acute or rapidly progressing onset of the gastrointestinal symptoms attributable to CD, requiring hospitalisation and/or parenteral nutrition along with at least two objective signs of malnutrition, dehydration or electrolyte imbalance.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In this disease, tTG normally have high titers, since the majority of patients who have a CC did not have a prior diagnosis of CD and, therefore, did not follow a GFD, although others may develop it after diagnosis when they do not adequately adhere to a GFD.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,8</span></a> The treatment for CC is a GFD, but some patients require steroids.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand, in light of the possibility that the initially positive tTG values could have been a false positive, given that they were negative a few days later, a differential diagnosis with RCD was suggested, after ruling out other conditions such as collagenous sprue, tropical sprue and bacterial overgrowth, among others.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">RCD is defined as the persistence of villous atrophy and clinical malabsorption that do not respond to a GFD. The refractory nature can be primary, if the patient never responded to the GFD, or secondary, if they had an initial response.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,10</span></a> It is a rare condition (1–1.5% of patients with CD).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> RCD can be classified as type <span class="elsevierStyleSmallCaps">I</span> or type <span class="elsevierStyleSmallCaps">II</span>. Type <span class="elsevierStyleSmallCaps">II</span> RCD is characterised by abnormal T-cells in the intestines and is associated with a higher mortality than type <span class="elsevierStyleSmallCaps">I</span> (56% vs. 7% at 5 years), mainly due to the risk of developing intestinal T-cell lymphoma.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> With respect to treatment, steroids briefly improve clinical symptoms in most patients, but normalisation of intestinal mucosa is rarely achieved and in most cases a dependency on steroids is observed.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The spectrum of disorders related to gluten constitutes a collection of complex diseases with limits that are not always defined. In our case, after having ruled out other causes of non-responsive CD and assuming that the initial tTG had actually been negative, the differential diagnosis with RCD was suggested. However, given an initially positive tTG and the excellent response to corticosteroids and, above all, having presented no relapses after the discontinuation of the corticosteroids, a diagnosis of CC is more probable.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lindo Ricce M, Rodriguez-Batllori Arán B, Jiménez Gómez M, Gisbert JP, Santander C. Enfermedad celíaca no respondedora: crisis celíaca vs. enfermedad celíaca refractaria con respuesta a corticoides. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 8 | 6 | 14 |
| 2024 September | 33 | 12 | 45 |
| 2024 August | 28 | 19 | 47 |
| 2024 July | 17 | 9 | 26 |
| 2024 June | 22 | 8 | 30 |
| 2024 May | 14 | 6 | 20 |
| 2024 April | 15 | 4 | 19 |
| 2024 March | 24 | 3 | 27 |
| 2024 February | 31 | 2 | 33 |
| 2024 January | 46 | 3 | 49 |
| 2023 December | 16 | 4 | 20 |
| 2023 November | 24 | 3 | 27 |
| 2023 October | 31 | 7 | 38 |
| 2023 September | 20 | 4 | 24 |
| 2023 August | 25 | 3 | 28 |
| 2023 July | 22 | 5 | 27 |
| 2023 June | 32 | 5 | 37 |
| 2023 May | 57 | 7 | 64 |
| 2023 April | 39 | 6 | 45 |
| 2023 March | 31 | 12 | 43 |
| 2023 February | 22 | 6 | 28 |
| 2023 January | 35 | 17 | 52 |
| 2022 December | 27 | 7 | 34 |
| 2022 November | 22 | 11 | 33 |
| 2022 October | 22 | 9 | 31 |
| 2022 September | 25 | 12 | 37 |
| 2022 August | 29 | 10 | 39 |
| 2022 July | 33 | 10 | 43 |
| 2022 June | 40 | 8 | 48 |
| 2022 May | 36 | 7 | 43 |
| 2022 April | 35 | 7 | 42 |
| 2022 March | 55 | 5 | 60 |
| 2022 February | 55 | 6 | 61 |
| 2022 January | 40 | 12 | 52 |
| 2021 December | 36 | 9 | 45 |
| 2021 November | 34 | 10 | 44 |
| 2021 October | 17 | 13 | 30 |
| 2021 September | 18 | 9 | 27 |
| 2021 August | 56 | 10 | 66 |
| 2021 July | 29 | 6 | 35 |
| 2021 June | 24 | 13 | 37 |
| 2021 May | 30 | 7 | 37 |
| 2021 April | 48 | 15 | 63 |
| 2021 March | 19 | 8 | 27 |
| 2021 February | 30 | 8 | 38 |
| 2021 January | 22 | 16 | 38 |
| 2020 December | 15 | 10 | 25 |
| 2020 November | 10 | 10 | 20 |
| 2020 October | 15 | 7 | 22 |
| 2020 September | 13 | 7 | 20 |
| 2020 August | 17 | 12 | 29 |
| 2020 July | 10 | 11 | 21 |
| 2020 June | 13 | 6 | 19 |
| 2020 May | 19 | 5 | 24 |
| 2020 April | 8 | 0 | 8 |
| 2020 March | 18 | 6 | 24 |
| 2020 February | 10 | 3 | 13 |
| 2020 January | 16 | 4 | 20 |
| 2019 December | 10 | 7 | 17 |
| 2019 November | 9 | 9 | 18 |
| 2019 October | 13 | 6 | 19 |
| 2018 July | 1 | 0 | 1 |
| 2017 October | 5 | 0 | 5 |
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