Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease

Penny, Hugo A; Baggus, Elisabeth M. R.; Rej, Anupam; Snowden, John A.; Sanders, David S.

doi:10.3390/nu12010216

Cited by 66 publications

(69 citation statements)

References 98 publications

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“…The causes of this problem are to be initially searched in an incorrect adherence to GFD and this is what can happen in those patients who still show persistently positive antibody titers and significant duodenal histological alterations, even despite quite a long period of GFD (>12 months). Furthermore, the possibility of refractory CD is always to be taken into consideration [4,[6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in clinically non-responding CD, other possible overlapping diagnoses should be considered, such as inflammatory bowel diseases (IBD), and irritable bowel syndrome (IBS)-like disorders (e.g., lactose intolerance), but many cases seem to remain unsolved [8]. Recently, a diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) has been proposed as an ex adiuvantibus treatment to reduce IBS-like symptoms in CD patients following a GFD, although there is no specific indication or supporting diagnostic test [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease

et al. 2020

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Background and Aim: Nickel (Ni)-rich foods can induce allergic contact mucositis (ACM) with irritable bowel syndrome (IBS)-like symptoms in predisposed subjects. Ni ACM has a high prevalence (>30%) in the general population and can be diagnosed by a Ni oral mucosa patch test (omPT). Many celiac disease (CD) patients on a gluten-free diet (GFD) often show a recrudescence of gastrointestinal and extraintestinal symptoms, although serological and histological remission has been achieved. Since a GFD often results in higher loads of ingested alimentary Ni (e.g., corn), we hypothesized that it would lead to a consequent intestinal sensitization to Ni in predisposed subjects. We wanted to (1) study Ni ACM prevalence in still symptomatic CD patients on a GFD and (2) study the effects of a low-Ni diet (LNiD) on their recurrent symptoms. Material and Methods: We recruited 102 consecutive CD patients (74 female, 28 male; age range 18–65 years, mean age 42.3 ± 7.4) on a GFD since at least 12 months, in current serological and histological remission (Marsh–Oberhuber type 0–I) who complained of relapsing gastrointestinal and/or extraintestinal symptoms. Inclusion criteria: presence of at least three gastrointestinal symptoms with a score ≥5 on the modified Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Exclusion criteria: IgE-mediated food allergy; history of past or current cancer; inflammatory bowel diseases; infectious diseases including Helicobacter pylori; lactose intolerance. All patients enrolled underwent Ni omPT and followed a LNiD for 3 months. A 24 symptoms questionnaire (GSRS modified according to the Salerno Experts’ Criteria, with 15 gastrointestinal and 9 extraintestinal symptoms) was administered at T0 (free diet), T1 (GFD, CD remission), T2 (recurrence of symptoms despite GFD), and T3 (GFD + LNiD) for comparisons. Comparisons were performed using Wilcoxon signed-rank test. RESULTS: Twenty patients (all female, age range 23–65 years, mean age 39.1 ± 2.9) out of 102 (19.6%) were finally included. All 20 patients enrolled (100%) showed positive Ni omPT, confirming an Ni ACM diagnosis. A correct GFD (T0 vs. T1) induced the improvement of 19 out of the total 24 (79.2%) symptoms, and 14 out of 24 (58.3%) were statistically significant (p-value < 0.0083 according to Bonferroni correction). Prolonged GFD (T1 vs. T2) revealed the worsening of 20 out of the total 24 (83.3%) symptoms, and 10 out of 24 (41.7%) were statistically significant. LNiD (T2 vs. T3) determined an improvement of 20 out of the total 24 (83.4%) symptoms, and in 10 out of 24 (41.7%) symptoms the improvement was statistically significant. Conclusions: Our data suggest that the recrudescence of gastrointestinal and extraintestinal symptoms observed in CD subjects during GFD may be due to the increase in alimentary Ni intake, once gluten contamination and persisting villous atrophy are excluded. Ni overload can induce Ni ACM, which can be diagnosed by a specific Ni omPT. Improvement of symptoms occurs after a proper LNiD. These encouraging data should be confirmed with larger studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease

et al. 2020

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“…Nonresponsive coeliac disease (NRCD) has been defined as the persistence of symptoms, signs, laboratory abnormalities, or histological changes typical of CD despite adherence to a GFD for 6–12 months [ 105 , 106 ]. We agree with this definition by Penny et al and we also agree on their statement that in this definition it is necessary to provide a timeframe, but this is inevitably arbitrary.…”

Section: Non-responsive Coeliac Diseasementioning

confidence: 99%

“…We agree with this definition by Penny et al and we also agree on their statement that in this definition it is necessary to provide a timeframe, but this is inevitably arbitrary. Not only the kinetics of clinical, histological, and serological response to a GFD is highly variable among coeliac patients, but also in the same patient the normalization of clinical, histological, and serological findings can occur at different time points [ 106 ]. Since in the Oslo classification a definition of NRCD was not provided [ 107 ], we consider the term NRCD as an “umbrella term” referring to variegated clinical scenarios, all characterized by an unsatisfactory clinical/histological response to a GFD, but totally different prognoses.…”

Section: Non-responsive Coeliac Diseasementioning

confidence: 99%

Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders

et al. 2020

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The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.

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“…The above listed complications as well as many others have been described in a sub-population of CD patients affected by non-responsive celiac disease (NRCD) that present persistent symptoms despite 6-12 months of gluten-free diet (34). While NRCD can be related to alternative primary diagnosis and associated conditions, a small percentage of patients are diagnosed with refractory celiac disease (RCD) (35).…”

Section: Compound Celiac Diseasementioning

confidence: 99%

Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies

2020

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Gluten related disorders (GRD), which include celiac disease, non-celiac wheat sensitivity and wheat allergy are heterogeneous conditions triggered by ingestion of glutencontaining grains. Together, their prevalence is estimated to be ∼5% in the general population, however, in the last years the number of diagnoses has been rapidly increasing. To this day, the gold standard treatment for these disorders is the complete removal of gluten-containing grains from the diet. Although this therapy results effective in the majority of patients, up to 30% of individuals affected by GRD continue to present persistent symptoms. In addition, gluten-free diet has been shown to have poor nutritional quality and to cause a socioeconomic burden in patients' quality of life. In order to respond to these issues, the scientific community has been focusing on finding additional and adjuvant non-dietary therapies. In this review, we focus on two main gluten related disorders, celiac disease and non-celiac wheat sensitivity. We delineate the actual knowledge about potential treatments and their relative efficacy in pre-clinical and clinical trials.

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Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease

Cited by 66 publications

References 98 publications

Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease

Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease

Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders

Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies

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