Study of the immune response in celiac patients with selective IgA deficiency who start a gluten-free diet.

Studies are scarce regarding IgG anti-tissue transglutaminase 2 (tTG) normalization in selective IgA deficient (SIgAD) celiac disease (CD) patients after beginning a gluten free diet (GFD). The aim of this study is to analyse the decreasing dynamics of IgG anti-tTG in patients diagnosed with CD who start a GFD. To achieve this objective, IgG and IgA anti-tTG levels at diagnosis and during follow-up in 11 SIgAD CD patients and in 20 IgA competent CD patients were retrospectively evaluated. At diagnosis, statistical differences were not found when comparing IgA anti-tTG levels of IgA competent subjects with IgG anti-tTG levels of SIgAD subjects. Regarding the decreasing dynamics, even though no statistical differences were found (p = 0.06), normalization rates were slower for SIgAD CD patients. After 1 and 2 years on GFD, respectively, only 18.2% and 36.3% of the SIgAD CD patients normalized IgG anti-tTG levels; otherwise, IgA anti-tTG reached values under the reference values in 30% and 80% of the IgA competent patients in the same time-points. Although IgG anti-tTG has demonstrated a high diagnostic efficiency in SIgAD CD pediatric patients, this test does not appear to be as precise for long-term GFD response monitoring as IgA anti-tTG levels in IgA sufficient patients.

Encephalopathy in short bowel syndrome: a diagnostic challenge.

A 15-year-old boy was admitted to the hospital due to ataxia, drowsiness and bradypsychia. He was known to have a short bowel syndrome Initial venous blood gases revealed a metabolic acidosis with a high anion gap of 24 mmol/L and normal L-lactate. He improved with fasting and fluids and was discharged with oral metronidazole. 2 weeks later he was admitted again with similar symptoms. A specific study of D-Lactic acidosis was carried out, confirming the diagnosis. D-lactic acidosis is an uncommon complication of short bowel syndrome. It occurs as a consequence of the metabolism of unabsorbed carbohydrates. The symptoms are mainly neurological. Limiting the dietary carbohydrates is useful to avoid recurrences. Poorly absorbable antibiotics are used but with varying results. Surgery may be an option if medical treatment fails. Probiotics might be useful to avoid symthoms recurrence.

Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions.

Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.

Screening-detected positive serology for celiac disease: a real clinical challenge.

According to European Society for Paediatric Gastroenterology, Hepatology, and Nutrition 2020 criteria for celiac disease diagnosis, the small bowel biopsy (SBB) can be omitted in selected circumstances, even in asymptomatic patients. Hence, we have conducted a retrospective study to identify the histological findings of the asymptomatic patients with antitransglutaminase IgA antibodies 10 times above the upper limit of normal and positive antiendomisium antibodies; 5/24 patients fulfilling these criteria had, however, a nonconclusive SBB and were diagnosed with potential celiac disease. The nonbiopsy approach in these cases needs to be carefully evaluated and the risk of overdiagnosis pondered as the management and evolution of potential celiac disease cases is still a matter of study.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

PURPOSE: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. METHODS: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. RESULTS: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. CONCLUSION: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

Recurrent Metabolic Alkalosis in a Cystic Fibrosis Patient: Coexistence with Congenital Chloride Diarrhea.

Metabolic alkalosis is uncommon in infancy. Cystic fibrosis (CF) patients can develop dehydration because of sweat salt or gastrointestinal losses; with the correct salt supplementation, the electrolyte alterations can be reversed. Here, we present a CF patient with recurrent metabolic alkalosis, initially oriented as pseudo-Bartter's syndrome. However, despite accurate treatment, patient needed daily intravenous fluids to maintain homeostasis. An extended study was made, including a urine study that could rule out Bartter's diagnosis. Finally, after a complementary test that included electrolyte stools study and genetic analysis, congenital chloride diarrhea could be diagnosed.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Common Problems Found in the Methodological Approach to Small Bowel Biopsies in the Diagnosis of Celiac Disease.

Small bowel biopsy (SBB) is not always helpful to establish celiac disease diagnosis. Hence we have conducted a retrospective study to know the amount of SBB in our center that was not optimal for this purpose. Histological findings were not appropriate for diagnosis in 3.56% (34 out of 955). The main problem encountered was inadequate sample cutting, although this could be solved by a new recut in almost 30% of cases.

Detection and quantification of gluten immunogenic peptides in feces of infants and their relationship with diet

Background: there are no effective methods to easily control the correct adherence to a gluten-free diet (GFD) in celiac disease (CD) patients. Aim: to assess the sensitivity and specificity of a rapid immunochromatographic (IC) test that detects gluten immunogenic peptides (GIP) in feces, compared to an enzyme-linked immunosorbent assay (ELISA) method. Methods: fecal samples from healthy infants were analyzed by a rapid IC test and ELISA, both methods are based on the anti-gliadin 33-mer monoclonal antibody. Group 1 included infants aged from 6 to 24 months, with an unrestricted consumption of gluten containing cereals. Group 2 (negative controls) was comprised of infants aged from 0 to 6 months, either breastfed or formula fed who had never ingested gluten. Results: in group 1 (n = 34), all infants had positive values by ELISA, the mean was 13.13 μgGIP/g (range 0.56-46.79). The IC test was negative in 5/20 cases and there was a significant correlation (p=0.006) between the mean daily gluten intake and GIP in feces. In group 2 (n = 20), all the samples were negative by both methods. Moreover, the Kappa Fleiss concordance index (Kappa = 0.79 CI95% [0.616, 0.965]) indicated a moderate concordance between both methods. Conclusions: according to our results, both methods are highly specific. However, the ELISA test had a higher sensitivity. Although we found a significant correlation between the amount of gluten consumed and GIP recovery in feces, further studies are needed to clarify the impact of individual confounding factors in GIP recovery

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Detection and quantification of gluten immunogenic peptides in feces of infants and their relationship with diet.

BACKGROUND: there are no effective methods to easily control the correct adherence to a gluten-free diet (GFD) in celiac disease (CD) patients. AIM: to assess the sensitivity and specificity of a rapid immunochromatographic (IC) test that detects gluten immunogenic peptides (GIP) in feces, compared to an enzyme-linked immunosorbent assay (ELISA) method. METHODS: fecal samples from healthy infants were analyzed by a rapid IC test and ELISA, both methods are based on the anti-gliadin 33-mer monoclonal antibody. Group 1 included infants aged from 6 to 24 months, with an unrestricted consumption of gluten containing cereals. Group 2 (negative controls) was comprised of infants aged from 0 to 6 months, either breastfed or formula fed who had never ingested gluten. RESULTS: in group 1 (n = 34), all infants had positive values by ELISA, the mean was 13.13 µgGIP/g (range 0.56-46.79). The IC test was negative in 5/20 cases and there was a significant correlation (p=0.006) between the mean daily gluten intake and GIP in feces. In group 2 (n = 20), all the samples were negative by both methods. Moreover, the Kappa Fleiss concordance index (Kappa = 0.79 CI95% [0.616, 0.965]) indicated a moderate concordance between both methods. CONCLUSIONS: according to our results, both methods are highly specific. However, the ELISA test had a higher sensitivity. Although we found a significant correlation between the amount of gluten consumed and GIP recovery in feces, further studies are needed to clarify the impact of individual confounding factors in GIP recovery.

Actualización en deficiencia de lipasa ácida lisosomal: diagnóstico, tratamiento y seguimiento de los pacientes / Update on lysosomal acid lipase deficiency: Diagnosis, treatment and patient management

La deficiencia de lipasa ácida lisosomal (DLAL) es una enfermedad ultrarrara causada por un error congénito del metabolismo lipídico, que se caracteriza por el depósito de ésteres de colesterol y triglicéridos en el organismo. En pacientes con nula función enzimática la enfermedad se inicia en el período perinatal y es inevitablemente mortal durante el primer año de vida. En el resto de los casos el fenotipo es heterogéneo, aunque la mayoría de los pacientes desarrollan hepatopatía crónica y pueden presentar enfermedad cardiovascular prematura. Clásicamente, el tratamiento de la DLAL ha consistido en el uso de medidas de soporte, que no evitan su progresión. En 2015, las agencias reguladoras aprobaron el uso de una LAL recombinante humana para el tratamiento de la DLAL. Dicho tratamiento de sustitución enzimática a largo plazo se ha asociado con mejorías significativas de los parámetros lipídicos y hepáticos, incrementándose la supervivencia en lactantes con enfermedad rápidamente progresiva. La gravedad de la enfermedad, junto con la reciente disponibilidad de un tratamiento específico, hace especialmente relevante la necesidad de identificar a estos pacientes en la práctica clínica, aunque la baja prevalencia de la DLAL y el solapamiento clínico con otras enfermedades más frecuentes dificulta su reconocimiento. Con base en la evidencia científica publicada y la experiencia clínica e investigacional de los autores, el presente documento incluye recomendaciones prácticas para la identificación y la monitorización de los pacientes con DLAL, incluyendo un algoritmo diagnóstico, junto con una actualización de su tratamiento (AU)

Lysosomal acid lipase deficiency (LALD) is an ultra-rare disease caused by a congenital disorder of the lipid metabolism, characterized by the deposition of cholesterol esters and triglycerides in the organism. In patients with no enzyme function, the disease develops during the perinatal period and is invariably associated with death during the first year of life. In all other cases, the phenotype is heterogeneous, although most patients develop chronic liver diseases and may also develop an early cardiovascular disease. Treatment for LALD has classically included the use of supportive measures that do not prevent the progression of the disease. In 2015, regulatory agencies approved the use of a human recombinant LAL for the treatment of LALD. This long-term enzyme replacement therapy has been associated with significant improvements in the hepatic and lipid profiles of patients with LALD, increasing survival rates in infants with a rapidly progressive disease. Both the severity of LALD and the availability of a specific treatment highlight the need to identify these patients in clinical settings, although its low prevalence and the existing clinical overlap with other more frequent pathologies limit its diagnosis. In this paper we set out practical recommendations to identify and monitor patients with LALD, including a diagnostic algorithm, along with an updated treatment (AU)

Update on lysosomal acid lipase deficiency: Diagnosis, treatment and patient management. / Actualización en deficiencia de lipasa ácida lisosomal: diagnóstico, tratamiento y seguimiento de los pacientes.

Lysosomal acid lipase deficiency (LALD) is an ultra-rare disease caused by a congenital disorder of the lipid metabolism, characterized by the deposition of cholesterol esters and triglycerides in the organism. In patients with no enzyme function, the disease develops during the perinatal period and is invariably associated with death during the first year of life. In all other cases, the phenotype is heterogeneous, although most patients develop chronic liver diseases and may also develop an early cardiovascular disease. Treatment for LALD has classically included the use of supportive measures that do not prevent the progression of the disease. In 2015, regulatory agencies approved the use of a human recombinant LAL for the treatment of LALD. This long-term enzyme replacement therapy has been associated with significant improvements in the hepatic and lipid profiles of patients with LALD, increasing survival rates in infants with a rapidly progressive disease. Both the severity of LALD and the availability of a specific treatment highlight the need to identify these patients in clinical settings, although its low prevalence and the existing clinical overlap with other more frequent pathologies limit its diagnosis. In this paper we set out practical recommendations to identify and monitor patients with LALD, including a diagnostic algorithm, along with an updated treatment.

Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. MATERIAL AND METHODS: We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. RESULTS: After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. CONCLUSION: Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Celiac disease: the new proposed ESPGHAN diagnostic criteria do work well in a selected population.

BACKGROUND: The need for an early and accurate diagnosis in celiac disease (CD) has focused attention on new diagnostic approaches, based on the efficiency of serological markers and the high negative predictive value of human leukocyte antigen (HLA) non-DQ2/8. METHODS: We performed a retrospective review of all of the patients suspected of having CD who had undergone a small bowel biopsy in our gastroenterology unit. All symptomatic children with serological marker at time of biopsy (immunoglobulin A-tissue transglutaminase antibody, endomysial antibody, and HLA genotype) were included. The triple test (TT) was positive if immunoglobulin A-tissue transglutaminase antibody was 10 times the upper limit of normal, plus positive endomysial antibody plus human leukocyte antigen-DQ2/DQ8. RESULTS: A total of 150 patients met the inclusion criteria and were enrolled in the study. One hundred sixteen were positive for the TT; 113 of 116 (97.4%) had a Marsh 2/3 histological lesion and had been considered to have CD. Thus, positive predictive value of the TT was 97.4%. The other 3 cases (2.6%) had Marsh 0/1 lesion, so we consider them to be false-positives for the TT; however, on follow-up, all 3 children developed histological damage after a gluten challenge. Finally, the positive predictive value of the TT was 100%. Thirty-four patients were negative for the TT: 22 patients are celiac, 3 are celiac but challenge gluten diet is pending, and the 9 patients left have other gastrointestinal disorder. CONCLUSIONS: Our study supports the view that in selected children who are symptomatic and positive for the TT, CD diagnosis could be established independent of histological findings.

Sesión de hemodiálisis en pacientes con peso inferior a 6 kilos / No disponible

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