Classical Celiac Disease Research Articles

Clinical Spectrum of Celiac Disease among Adult Population: Experience from Largest Tertiary Care Hospital in Karachi, Pakistan.

Celiac disease (CD) is a systemic autoimmune enteropathy triggered by dietary gluten in genetically susceptible individuals. Celiac disease affects 0.6-1.0% of the population worldwide. The prevalence of CD in Pakistan is yet unknown due to under diagnosis and lack of awareness. To determine a vast variety of presenting features in subtypes of CD to overcome the burden of disease. This was a prospective, comparative, cross-sectional study conducted at Gastroenterology department of Jinnah Postgraduate Medical Center, Karachi from December 2022 till June 2023. This study included all adult patients ≥18 years diagnosed with CD on the basis of clinical presentation, positive IgA and IgG anti-transglutaminase antibodies (value >12 IU/mL detected by ELISA followed by small intestinal biopsy classified as per Marsh criteria. The data obtained were analyzed on the statistical software SPSS version 23. Descriptive statistics were obtained by frequencies and percentages. About 142 patients were enrolled in the study, 103 (91.5%) had classical CD (CCD) whereas 36 (25%) had non-classical (NCCD). About 89 (62.7%) were females and 53 (37.3%) were males. The mean age was found to be 23 ± 6 years. Nutritional deficiencies including anemia, B12, folate, osteopenia and low body mass index (BMI) <18 was found more in CCD group as compared with NCCD group with significant p-values. Titers of anti-TTG between CCD and NCCD were not statistically significant. Hypothyroidism and PCOS were the most common associated conditions observed in adult CD patients. In conclusion, CD in adults and has diverse presentations. Adults with unexplained extra-intestinal symptoms like anemia and bone pain should be investigated for CD. Butt N, Shahid B, Butt S, et al. Clinical Spectrum of Celiac Disease among Adult Population: Experience from Largest Tertiary Care Hospital in Karachi, Pakistan. Euroasian J Hepato-Gastroenterol 2024;14(1):24-29.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Nomenclature and diagnosis of seronegative celiac disease and chronic non-celiac enteropathies in adults

Small bowel villous atrophy is one of the main histopathological manifestations of chronic enteropathy. In most cases, this condition is caused by celiac disease. Celiac disease is an autoimmune disease that occurs in genetically predisposed individuals and is characterized by damage to the mucous membrane of the small intestine (T-cell-mediated enteropathy) due to the influence of gluten and is treated with the help of a lifelong gluten-free diet. Diagnosis of classic celiac disease does not cause difficulties. Diagnostic algorithms have been developed for years. Diagnostic problems arise when small bowel villous atrophy occurs in patients who have gastrointestinal symptoms but are negative for celiac disease-specific antibodies. Differential diagnosis of small bowel villous atrophy without serological markers for celiac disease in adults includes seronegative celiac disease and chronic non-celiac enteropathies. There has long been diagnostic and clinical uncertainty about these conditions. This uncertainty has led to misdiagnoses and increased the number of people following a gluten-free diet unnecessarily. Between September 2019 and July 2021, an international working group of 13 gastroenterologists from six countries worked to create a consensus on the nomenclature and diagnosis of seronegative celiac disease and non-celiac enteropathies in adults.

Diagnostic challenges in children with celiac disease. A five-year experience with new guidelines in a General Pediatrics Department

Background. The clinical characteristics of patients with celiac disease cover a wide range of signs and symptoms. Our study aimed to describe the main clinical features and investigations performed on our celiac patients diagnosed in the past five years. Material and methods. We collected data from medical records of patients aged 0 to 18 years diagnosed with celiac disease. We included in the analysis patients newly diagnosed with celiac disease, in our department, between January 2017 and August 2022. Results. In this period, 30 children were diagnosed with celiac disease in our general pediatrics department. The mean age at diagnosis ± standard deviation was 6.3±4.2 years (median age=4.3 years). The period between onset of symptoms ranged between 3 months to 5 years (median=6 months). Twenty children (66%) had features of classical celiac disease. Thirteen/30 patients (43.3%) were found to have iron deficiency anemia at diagnosis. In 23/30 (76%) of the children, the values of the IgA-TGA were more than 10 times the upper limit of the normal values. Nineteen children were diagnosed between 2017 and 2019. Fifteen of these 19 patients (79%) were diagnosed based on positive levels of antibodies and duodenal biopsy samples showing Marsh 2 or 3 features, and 4/19 (21%) based on positive IgA-TGA and AEM and a genetic test showing HLA DQ2 and/or DQ8. Conclusions. Classical celiac disease remains the predominant phenotype in our patients. Adherence to new guidelines allowed in the past 2 years a diagnosis without histological examination of biopsy fragments in most of the patients.

Clinical Presentation Is Dependent on Age and Calendar Year of Diagnosis in Celiac Disease: A Hungarian Cross-Sectional Study.

International trends indicate that celiac disease (CeD) is becoming more common, while the clinical presentation of CeD tends to change. We aimed to investigate factors associated with the clinical presentation of CeD. We reviewed all CeD cases diagnosed at our tertiary center, University of Pécs (Hungary), between 1992 and 2019. We collected data of verified CeD patients on clinical presentations (classified by the Oslo Classification), the age at and calendar year of diagnosis, and sex, serology and histology at diagnosis. To assess the associations of baseline variables with clinical presentations, we applied univariate and multivariate (binary logistic regression) statistics. A total of 738 CeD patients were eligible for inclusion. In the univariate analysis, patients with classical CeD were more common in the latest calendar period (p < 0.001) and tended to be older (p = 0.056), but we failed to observe a significant association between the clinical presentation and sex, serology or histology at diagnosis. In the multivariate analysis, only age at diagnosis and calendar year were independently associated with clinical presentations (OR = 1.02, CI: 1.01-1.04 and OR = 0.93, CI: 0.89-0.98, respectively). Our findings confirmed that classical CeD is independently associated with age at diagnosis and calendar year of diagnosis of CeD, whereas other parameters were not significantly associated with clinical presentations.

Clinical and endoscopic characteristics of adult celiac disease

Objective: The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment. Methods: In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed. Results: A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant (P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD (P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions: Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

Rapid Immunochromatography on Fresh Intestinal Biopsy Is Highly Accurate in Detecting Intestinal Antitransglutaminase Antibodies.

Intestinal antitransglutaminase antibodies (I-anti-TG2) are a specific marker of celiac disease (CeD). The aim of this study was to evaluate the diagnostic accuracy of a novel application of an immunochromatographic assay referred to as Rapid_AntiTG2 to detect I-anti-TG2 on intestinal biopsy lysate. Consecutive pediatric patients referred to a single center for elective upper endoscopy were enrolled. Biopsies were taken from duodenal bulb and distal duodenum. For each sampling site, 2 biopsies were analyzed for standard histology, 1 biopsy was cultured to perform the reference standard assay for I-anti-TG2 detection (endomysium [EMA] biopsy), and 1 biopsy was mechanically lysed to perform Rapid_AntiTG2. The primary outcome was the diagnostic accuracy of Rapid_AntiTG2 on biopsy lysate compared with that of the gold standard (serology + histopathology) for CeD diagnosis. The secondary outcome was the agreement of Rapid_AntiTG2 with EMA biopsy. One hundred forty-eight patients were included. Of them, 79 were those with CeD (64 classical CeD, 2 seronegative CeD, and 13 potential CeD) and 69 were controls. Rapid_AntiTG2 on biopsy lysate had very high diagnostic accuracy (sensitivity 100%, specificity 97%, LR+ 34.1, LR- 0.01) in separating patients with CeD from controls. Diagnostic accuracy was unchanged in patients with potential and seronegative CeD. Rapid_AntiTG2 on biopsy lysate had almost perfect agreement with the EMA biopsy reference test (99% agreement, Cohen K 0.97). I-anti-TG2 can be detected with an immunochromatographic assay after simple mechanical lysis of fresh intestinal biopsy with very high diagnostic accuracy. The test is quick and easy to perform and can be widely available in any endoscopy unit. Its implementation would allow a better understanding of the prognostic value of I-anti-TG2 and help clinicians in cases of suspected CeD that are difficult to classify.

Spanish National Registry of Paediatric Coeliac Disease: Changes in the Clinical Presentation in the 21st Century.

Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain. A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected. In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines. Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.

Assessment of the Predictive Factors Influencing the Diagnosis and Severity of Villous Atrophy in Patients with Celiac Disease and Iron Deficiency Anemia Referred for Diagnostic Endoscopy in Basrah, Iraq

Background: The classic celiac disease (CD) presentation in individuals with iron deficiency anemia (IDA) has been changed given the large percentage of subtle or asymptomatic cases. The study objective was to assess the predictive factors influencing the diagnosis and severity of villous atrophy in individuals with CD and IDA referred for a diagnostic endoscopy. Methods: This was a retrospective observational, cross-sectional analysis of the medical records of 499 individuals with IDA in 2 centers in Basrah, Iraq, who referred for possible diagnosis of CD within 10 years (2006-2016). The relationship of the severity of anemia, demographic characteristics, symptomatology, and celiac serological results on the final diagnostic endoscopic evaluation was evaluated using a univariate analysis, at a P value ≤ 0.05. The study adopted the Marsh classification for celiac disease diagnosis where Marsh type 3 represents the definite celiac disease. Results: The definite diagnosis was seen in 44.5% of the cohort (n = 222), with asymptomatic cases representing 22.5% of cases (n = 50). The mean age was (27 ± 11) years, with significant association to (female gender, age ≤45 years, positive celiac serology, and severity of anemia). After adjustment of the variables, the Marsh type was significantly correlated with positive celiac serology, low hemoglobin, and presence of gastrointestinal symptoms. Conclusion: The positive celiac serology, low hemoglobin <9 g/L, and the presence of gastrointestinal symptoms are strong predictors of the severity of villous atrophy (Marsh type).

Histological Features of Celiac-Disease-like Conditions Related to Immune Checkpoint Inhibitors Therapy: A Signal to Keep in Mind for Pathologists.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1), and its ligand PDL-1, are finding increasing application in the treatment of malignant neoplasms. The widespread clinical use of these drugs, however, resulted in the discovery of side effects. The occurrence of celiac disease (CD) after ICIs therapy has been reported in the literature, but its incidence remains unknown and the role of ICIs in its onset is not yet clear. In this review, we examine the published data on this topic in order to better understand and define this entity from a histological point of view. We performed an electronic literature search to identify original reports in which CD or pathological CD-like conditions were documented histologically in patients treated with ICIs. We identified ten papers. A total of twenty-five patients were included in these publications, eleven of them receiving a serologic and histological diagnosis of CD, and four a histological diagnosis of CD-like conditions, in which pathogenesis appears to be multifactorial. ICIs can cause a CD-like enteropathy and biopsies with clinical integration are crucial to diagnose this condition. CD rarely has been observed during treatment with ICIs and its morphological aspects are similar to ICIs-CD enteropathy. Moreover, the onset of ICIs-CD may have a distinct immune mechanism compared to classical CD. Thus, the pathologists must make a histological diagnosis of CD with caution and only in adequate clinical and serological context.

Quality of Life and Psychological Disorders in Coeliac Disease: A Prospective Multicentre Study

Coeliac disease (CeD) has been associated with psychological disorders and reduced quality of life. Our prospective study evaluated the changes in the quality of life, anxiety and depression in CeD patients up to two years after diagnosis. We recruited adult patients residing in the Veneto region with a new diagnosis of CeD. Several validated questionnaires were administered to measure quality of life, psychological symptoms and adherence to a gluten-free diet (GFD) at the time of diagnosis and after 1 and 2 years. Ninety-three patients reached the 1-year follow-up (81.7% were females with a median age at diagnosis of 35 years), and 55 patients reached the 2-year follow-up. We observed a significant improvement in quality of life, anxiety and depression scores at 1 year after diagnosis, particularly in patients who complied with a GFD. The improvements among classical CeD patients were similar to those observed in nonclassical patients except for anxiety, which improved only in patients with a classical presentation at diagnosis. Age, sex and other disease factors did not affect the change in quality of life (QoL) or other mood disorders. Most of the improvements measured 1 year after diagnosis and 2 years after diagnosis were not significant. In conclusion, QoL and mood disorders must be considered, and psychological counselling should be used when needed.

Celiac Disease among Adults and Children in AL-Anbar Province West of Iraq: a Comparative Cross-Sectional Study

Background: gluten-sensitive Enteropathy is a public non-communicable, immune-associated disease whichis activated by wheat (gluten) ingesting that occur in hereditarily susceptible individuals in initial childhood&amp; elderly individuals with varied presentations whereas several studies have shown CD are predominantin adults. The purpose of this study was to compare the clinical presentation, serological, endoscopic, andhistopathological features in adults and children with celiac disease at Al-Anbar province, west of Iraq. Atotal of 170 consecutive newly confirmed CD patients in AL-Ramadi teaching hospital, GastroenterologyClinic during a period between August 2017 &amp; Jun 2020 had been involved in comparative cross-sectionaldesign research. Patients were divided into two groups: adults and children and each of them was alsodivided into two groups- classical and non-classical celiac disease based upon the clinical presentation.Clinical presentation, endoscopic findings were recorded.in all cases gastrointestinal endoscopy &amp; duodenalbiopsy with Anti -TTG lgA had been determined &amp; tested for the CD diagnosis. Histopathology results hadbeen divided using modified Marsh taxonomy. Results had been examined through a suitable statisticaltest. Of 170 CD patients that include 97 (57.1%) adults CD and 73(42.9) children. Classical symptomswere predominant among 85.56% of adults while non-classical symptoms were more common among45.2% of children. Bloating with abdominal pain and anemia were predominant among adults and childrenrespectively. No significant differences in the Levels of anti –tTG among each of adults and a pediatricgroup of CD patients (P-Value 0.072). The most common endoscopic finding was scalloping 60.3%, 40.2%)among children and adults respectively. Marsh grade G3A were predominant among adults [83 (89.2%)]versus [67 (95.7%)] among children of CD patients with anti-tTG lgA U/ml 10+1 and more levels.No statistical difference regarding marsh grade G3 frequency among adults and children CD patients (p0.191).

Современное состояние диагностики целиакии в Узбекистане: проблемы и решения

Objective. To study the state of diagnosis, clinical manifestation and laboratory changes in children with celiac disease in the Republic of Uzbekistan. Patients and methods. The article presents a description of 64 newly diagnosed cases of celiac disease registered in the Republican Specialized Scientific and Practical Medical Center of Pediatrics. Celiac disease was diagnosed according to the ESPGHAN criteria. Results. Out of 64 patients, celiac disease was more frequently diagnosed among girls (69.6%), the median age at diagnosis was 5.3 ± 0.6 years. Classic symptoms were observed in 46 (71.9%) patients, the number of patients with extraintestinal manifestations was 18 (28.1%). In classical celiac disease, the most common intestinal symptoms were bloating, diarrhea, and severe protein-energy malnutrition (p ≤ 0.05; p ≤ 0.0001). Among the patients with extraintestinal manifestations, there were more often children with subnanism (p ≤ 0.05). Hemoglobin and calcium levels decreased with the same frequency in atypical and typical forms of celiac disease; there was an increase in the level of alkaline phosphatase in both groups, but higher amounts were found in typical forms of the disease. The majority of patients had a histological study of the intestinal mucosa according to Marsh III, most commonly – IIIc (total villous atrophy). Conclusion. The diagnosis of celiac disease in children living in Uzbekistan is established with a considerable delay. Most patients have classic symptoms accompanied by intestinal manifestations. It is essential to be alert to the diagnosis of celiac disease in patients with extraintestinal manifestations in the absence of diarrhea. In this regard, it is necessary to raise doctors’ awareness of the diagnosis of atypical forms of the disease, as well as to improve their knowledge about different manifestations of celiac disease. Key words: celiac disease, extraintestinal manifestations, children, diagnosis

The Presentation Pattern of Celiac Disease in Central India –A Prospective Study in Children

Introduction: Celiac disease is a common immune-mediated enteropathy characterised by villous atrophy. It has clinical phenotypes of classic, non-gastrointestinal and silent/subclinical or potential depending on the clinical phenotype. We intended to assess the clinical features and laboratory findings of patients with celiac disease and compare the classical celiac disease with non-gastrointestinal celiac disease. &#x0D; Methods: This is a two-year cross-sectional study conducted at our institute. Children from one year to 18 years diagnosed as celiac disease based on the revised ESPGHAN criteria were enrolled. They were categorised into classical celiac disease and non-gastrointestinal celiac disease (atypical) and their clinical features and laboratory findings were documented. &#x0D; Results: Forty patients had confirmed celiac disease. The mean age of the subjects was 6.84 ± 4.41 years, with male: female ratio of 1.85. The commonest presentations were failure to thrive (75%), anaemia (70%), associated rickets (67.5%) and 32% diarrhoea. Patients with classical features were identified at an earlier age than those with non-gastrointestinal celiac disease. Marsh grade 3a and above were more commonly seen in classical celiac disease. The most common symptom among the classical group was abdominal distension. Among the non-gastrointestinal group, the most common symptom was anaemia. Vitamin D deficiency was almost equally present in both groups. &#x0D; Conclusions: Non-gastrointestinal celiac disease is not uncommon among our population. Patients with clinical features of recurrent abdominal pain, vomiting, failure to thrive, or merely short stature and refractory anaemia should be worked up for celiac disease.

Rotavirus gastroenteritis as a precipitating factor of celiac crisis in infancy: Case reports and review of literature

Introduction. Celiac crisis is a rare and life-threatening complication of celiac disease. Although it occurs in all ages, the most common affects children within the first two years. Outline of cases. We report three infants (two female, one male, age range 9?12) with celiac crises as an initial presentation of celiac disease precipitated with rotavirus gastroenteritis. Celiac crisis was preceded by failure to thrive caused by anorexia, occasional vomiting and frequent abundant stools for 4?8 weeks, and 1?2 days before admission with fever, frequent vomiting and profuse watery diarrhea. They were admitted in a very severe general condition, severely dehydrated, markedly malnourished, with an enormously distended abdomen, edema of the lower legs and feet, and perianal erythema. After correction of dehydration and hypoalbuminemia, they were placed on a gluten- and disaccharide-free diet and within the first two weeks on additional parenteral nutrition. The applied therapeutic measures resulted in stabilization and further rapid improvement of the patient?s condition. In all three patients the latex agglutination test for rotavirus was positive, IgA anti-TTG antibodies elevated (58.6?78 U/ml) and all three were homozygous carriers of the HLA DQ2 gene. Enterobiopsy was performed two weeks after the admission and total villous atrophy (Marsh IIIc) was registered in all three patients. In the further course, the complete recovery of the patient was accomplished by a strict gluten-free diet. Conclusion. Our experience indicates that rotavirus gastroenteritis in timely unrecognized classical celiac disease in infants can lead to celiac crisis.

Estudios clínicos sobre la enfermedad celíaca (2014-2019): revisión sistemática de la prevalencia de la presentación clínica y enfermedades asociadas por edades

Introducción: La enfermedad celíaca (EC) se caracteriza por una gran variedad de signos, síntomas y enfermedades asociadas en su forma de presentación, incluso puede cursar de forma asintomática. Recientes estudios muestran la variación del espectro clínico según la edad. En niños y niñas pequeñas predomina la forma clásica con síntomas como distensión abdominal, disminución del apetito, diarrea y pérdida de peso. Las manifestaciones atípicas frecuentes en niños mayores son dolor abdominal, estreñimiento, reflujo, vómitos, fatiga, talla baja. En adultos se observa una reducción de la forma de presentación clásica e incremento de la no clásica.Material y métodos: Se realizó una revisión sistemática en la que se han incluido los artículos sobre signos y síntomas de la EC clásica y atípica en niños y adultos, además de las enfermedades que se asocian de forma frecuente a esta patología. Las bases de datos utilizadas para la búsqueda de los artículos fueron PubMed, Web of Science y Scopus, de los últimos seis años (2014-2019). Se han evaluado un total de 164 artículos tras los criterios de selección, de los cuales se han incluido en el estudio los 20 artículos más relevantes.Resultados: La EC se diagnostica con mayor frecuencia en mujeres y a edades más tempranas que a los hombres. En niños menores de dos años predomina la EC clásica, aunque de forma más intensa que en niños y niñas pequeñas. En niños y niñas mayores, adolescentes y edad adulta varía la forma de presentación hacia la atípica o no clásica y asintomática.Conclusiones: El incremento en la prevalencia en los últimos años, gran heterogeneidad de síntomas, enfermedades asociadas y la variación del espectro clínico hacia una forma atípica con síntomas extraintestinales causa retraso en su diagnóstico por lo que deben reconocerse para que se detecte de manera más precoz.

Immune checkpoint inhibitor-associated celiac disease.

BackgroundRare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD.MethodsA medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student’s t-test and Fisher’s exact test.ResultsThe eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3+ CD8+ T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms.ConclusionsICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.

Diagnostic accuracy and applicability of intestinal auto-antibodies in the wide clinical spectrum of coeliac disease.

BackgroundIntestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD.MethodsIntestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects.FindingsTwo-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%).InterpretationIntestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations.FundingInterreg Central-Europe, IRCCS “Burlo Garofolo”.

Effect of a Gluten-free Diet on Quality of Life in Patients With Nonclassical Versus Classical Presentations of Celiac Disease.

Celiac disease (CD) often presents with symptoms of diarrhea and malabsorption, termed classical CD. However, it can also present as nonclassical CD, which is commonly associated with nongastrointestinal symptoms. Studies suggest that nonclassical CD tends to have less severe symptoms than classical CD, which may affect both adherence to a gluten-free diet (GFD) and psychological stress. Therefore, we compared adherence to a GFD and psychological measures, including quality of life (QOL) and somatization, between patients with nonclassical and classical presentations of CD. Patients at a tertiary care center with biopsy-proven CD, who completed a Talley Bowel Disease Questionnaire and the Short Form-36 at diagnosis and who had been on a GFD for at least 1 year, were included in this study. Patients were further surveyed to assess gastrointestinal symptoms, QOL, Somatization Symptom Checklist (SSC), and adherence to a GFD. Results were compared between patients with classical versus nonclassical CD presentation. Among 122 patients included in this study, 62 had classical CD and 60 had nonclassical CD. At diagnosis, health-related QOL was lower in the classical CD group than in the nonclassical CD group. After following a GFD, both groups had improved QOL after following a GFD, and body mass index significantly increased in both groups. Most subscales of QOL, SSC scores, and adherence to the GFD were similar between the groups, except the Short Form-36 Mental Component summary scores that were still lower in the classical CD (48.4 vs. 52.6 nonclassical CD group; P=0.03). Despite QOL at diagnosis being higher in those with nonclassical CD versus lower in those with classical CD, both groups had improved QOL and achieved a similar QOL after following a GFD.

Gluten-induced Distal Tubular Acidosis?

The expanding spectrum of gluten-related autoimmune disorders may encompass distal tubular acidosis. We report a case of an infant presenting a classical digestive celiac disease along with a transient, reversible tubular acidosis that vanished after gluten free diet.