Refractory Celiac Disease: Epidemiology and Clinical Manifestations

Malamut, Georgia; Cellier, Christophe

doi:10.1159/000369519

Cited by 23 publications

(9 citation statements)

References 42 publications

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“…The major problems in clearly defining such a risk come from the difficulty to distinguish between diagnosed and undiagnosed CD patients, patients with different CD sub-types, and to extrapolate those patients affected by refractory celiac disease (RCD) from the population database. RCD, although rare (less than 1% of CD patients), presents a very high risk of malignant transformation and consequently a high mortality rate: the presence of RCD in the analyzed cohorts could represent a bias in studies investigating mortality in CD [29,30]. If some studies showed a fourfold increased mortality in CD [31,32], mainly due to lymphoma, without demonstrating a clear connection with gluten exposure, often only indirectly suggested [33], other studies have failed to confirm this scenario [34].…”

Section: Discussionmentioning

confidence: 99%

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study

Elli

Bascuñán

Lernia

et al. 2020

BMC Med

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Background: Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary and occasional transgressions to their GFD. Methods: From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls. Results: One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population. Conclusions: Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached.

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Section: Discussionmentioning

confidence: 99%

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study

Elli

Bascuñán

Lernia

et al. 2020

BMC Med

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“…Despite a growing understanding of its pathogenesis, type II RCD remains a challenging condition because no standardized treatment is available and patient outcome is burdened by a high mortality rate due to the frequent progression into enteropathy-associated T-cell lymphoma. 1,2 The few cases in which recovery from malnutrition with improvement of mucosal architecture has been observed were those treated with hematopoietic stem cell transplant, 6,7 and all the other therapeutic options have proved unfruitful. 4 However, in view of the aggressiveness of bone marrow transplant, alternative and safer strategies are eagerly awaited.…”

Section: Discussionmentioning

confidence: 99%

“…R efractory celiac disease (RCD) is a condition defined by the persistence or recurrence of malabsorption syndrome and intestinal villous atrophy despite a strict gluten-free diet for more than 12 months. 1 Its hallmark is an accumulation of aberrant intraepithelial lymphocytes (IELs), the amount of which makes it possible to differentiate between type I and type II RCD. 2 The latter is burdened by a poor prognosis because of severe malnutrition, frequent infections, and a high risk of overt lymphoma, leading to a 5-year survival rate less than 50%.…”

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confidence: 99%

“…2 The latter is burdened by a poor prognosis because of severe malnutrition, frequent infections, and a high risk of overt lymphoma, leading to a 5-year survival rate less than 50%. 1 Interleukin (IL)-15 plays a pivotal role in promoting T-cell cytotoxicity, survival, and lymphomagenesis, 3 although the therapeutic use of its blocking agents is still awaited. Therefore, the current treatment is based on the use of nontargeted immunomodulating agents that do not substantially modify the patients' outcome, 4 and autologous hematopoietic stem cell transplant, although performing better, 5,6 cannot be applied in all cases because of the substantial risk of morbidity and mortality in this clinical setting.…”

mentioning

confidence: 99%

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A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions

Ciccocioppo

Gallia

Avanzini

et al. 2016

Mayo Clinic Proceedings

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Type II refractory celiac disease (RCD), as defined according to the amount of aberrant intraepithelial lymphocytes, is a condition characterized by severe malabsorption syndrome and poor prognosis, with no effective treatment. Based on the regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs), we investigated the feasibility, safety, and efficacy of serial infusions of autologous bone marrow-derived MSCs in a 51-year-old woman with type II RCD. Mesenchymal stem cells were isolated, expanded, and characterized following standard protocols. Monitoring of the patient's malabsorption indexes, mucosal architecture, and percentage of aberrant intraepithelial lymphocytes was scheduled for the time of enrollment, at each infusion, and after 6 months. Determination of mucosal expression of interleukin (IL)-15 and its receptor was also performed. Expansion of MSCs was feasible, and the patient underwent 4 systemic infusions of 2 × 10(6) MSCs/kg body weight 4 months apart, without adverse effects. During the treatment period, she experienced gradual and durable amelioration of her general condition, with normalization of stool frequency, body mass index, laboratory test results, and mucosal architecture. Remarkably, the expression of IL-15 and its receptor almost completely disappeared. Thus, treatment of RCD with serial MSC infusions seems promising, leading to recovery from the life-threatening condition while blocking the IL-15 pathogenic pathway.

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“…Refractory celiac disease (RCD) is defined as the persistence or recurrence of clinical symptoms of malabsorption and typical histological signs of celiac enteropathy despite a strict gluten-free diet (GFD) for 12 months or longer [1,2,3]. The cumulative incidence was reported to be up to 1 % of all patients with celiac disease, implying that it affects around 0.01 % of the population [4,5].…”

Section: Introductionmentioning

confidence: 99%

Results from the German registry for refractory celiac disease

et al. 2021

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AbtractRefractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management.

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Refractory Celiac Disease: Epidemiology and Clinical Manifestations

Cited by 23 publications

References 42 publications

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study

A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions

Results from the German registry for refractory celiac disease

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