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Revista Espanola de Enfermedades... Nov 2023Autoimmune enteropathy is a rare intestinal disease. Here we report an elderly female with autoimmune enteropathy and primary biliary cholangitis who presented with...
Autoimmune enteropathy is a rare intestinal disease. Here we report an elderly female with autoimmune enteropathy and primary biliary cholangitis who presented with chronic diarrhea, malnutrition and severe hypokalemia and metabolic acidosis. Enteroscopy showed atrophied small intestinal villi with scallop-like and fissure-like changes. Hormone treatment relieved diarrhea. Four months later, she developed primary biliary cholangitis, and the liver function returned to normal after treatment with ursodeoxycholic acid, corticosteroids and immunosuppressants.
Topics: Aged; Humans; Female; Liver Cirrhosis, Biliary; Polyendocrinopathies, Autoimmune; Atrophy; Diarrhea; Rare Diseases
PubMed: 37771301
DOI: 10.17235/reed.2023.9901/2023 -
Revista Espanola de Enfermedades... Oct 2023Olmesartan-induced enteropathy (OIE) is an emergent enteropathy related to this angiotensin II receptor blocker. Main clinical manifestation is chronic diarrhea and...
Olmesartan-induced enteropathy (OIE) is an emergent enteropathy related to this angiotensin II receptor blocker. Main clinical manifestation is chronic diarrhea and duodenal biopsy is characterized by villous atrophy. Therefore, it is necessary to exclude other causes of enteropathy such as celiac disease, autoimmune enteropathy, intestinal lymphoma, parasitic infections, immunodeficiencies, or Crohn disease. Although it is supposed to be triggered by an immune mechanism, it is not clear its relation to other autoimmune disorders. We report for the first time a case of OIE associated with antiphospholipid syndrome.
PubMed: 36633177
DOI: 10.17235/reed.2022.9427/2022 -
BMC Pediatrics Nov 2023Autoimmune enteropathy (AIE) defined by intractable diarrhoea and nonceliac enteropathy with villous atrophy, is a rare digestive disease. Case reports of this disease... (Review)
Review
BACKGROUND
Autoimmune enteropathy (AIE) defined by intractable diarrhoea and nonceliac enteropathy with villous atrophy, is a rare digestive disease. Case reports of this disease are sporadic and the clinical characteristics of AIE is seldom discussed.
PURPOSE
We evaluate the clinical, laboratory, histopathological features, response to therapy and outcome of AIE in children.
METHOD
We conducted a retrospective analysis of five children with AIE in our hospital. A comprehensive search of MEDLINE was performed using PubMed, through keywords of "autoimmune enteropathy, pediatric or children". The clinical manifestations, endoscopic results, pathological results, and medication therapy of these children were collected and the cases were divided into two groups, infants (≤ 1 year old) and children (> 1 year old).
RESULTS
Five cases treated in our department: one case took eight years to make the final diagnosis; one case was positive for anti-intestinal epithelial cell (AE) antibody; three cases showed crypt apoptosis in histopathology; and two cases showed celiac-like changes. All cases were responsive to glucocorticoid therapy in the early stage of treatment, while three cases required immunosuppressant maintenance. After reviewing the literature, we performed a statistical analysis of 50 cases with a male-to-female ratio of 31:19. Among them, 35 patients (70%) were within 1 year of age, and their clinical manifestations were mainly watery stool (43 cases, 86%), weight loss (28 cases, 56%), abdominal distension (3 cases, 6%), serum AE or anti-goblet cell (AG) antibody positivity (32 cases, 64%), other immune-related antibodies (21 cases, 42%), gene mutations (9 cases, 18%), and family history (21 cases, 42%). All the children showed different degrees of intestinal villous atrophy. Thirty-seven (74%) of the children were treated early, and their clinical symptoms were relieved. Comparing the cases between different age groups, it was found that the mortality rate of children with onset in infancy was higher (P < 0.05), and there was no difference in other autoimmune diseases, AE antibody positivity rates, and other antibodies between the two groups. In addition to survival rate between different age group (P = 0. 005), there was no difference in sex, autoantibody positivity rate, single gene mutation, or family history between the two groups (P > 0.05) through analysis of mortality and clinical remission cases.
CONCLUSION
Endoscopic examination and mucosal pathological examination should be performed to diagnose AIE in children with watery stool and weight loss who fail to be treated with diet therapy. Immunotherapy is the core of medical management of AIE and can improve prognosis. Children with a poor prognosis in infancy should be actively treated to reduce mortality rates associated with AIE.
Topics: Infant; Humans; Child; Male; Female; Retrospective Studies; Polyendocrinopathies, Autoimmune; Intestinal Diseases; Diarrhea; Atrophy; Weight Loss
PubMed: 38017413
DOI: 10.1186/s12887-023-04435-x -
Journal of Gastrointestinal and Liver... Jun 2023A 74-year-old woman was admitted for weight loss, abdominal pain and diarrhea for a year. Blood tests showed elevated transaminases, cholestasis and hyperbilirubinemia....
A 74-year-old woman was admitted for weight loss, abdominal pain and diarrhea for a year. Blood tests showed elevated transaminases, cholestasis and hyperbilirubinemia. Capsule endoscopy revealed extensively scattered lymphangiectasias, shortened villi and erosions in the jejunum and ileum. The histological examination of the small bowel mucosa biopsies evidenced severe mucosal atrophy and crypt hyperplasia, without significant intraepithelial lymphocytosis. The clinical picture, lack of response to a gluten-free diet and endoscopic and histopathologic findings were compatible with autoimmune enteropathy. Simultaneously, autoimmune hepatitis was also diagnosed. The patient showed significant improvement after starting treatment with prednisolone and azathioprine. To our knowledge, this is the first case of autoimmune enteropathy diagnosed simultaneously with autoimmune hepatitis.
Topics: Female; Humans; Aged; Hepatitis, Autoimmune; Polyendocrinopathies, Autoimmune; Intestinal Mucosa; Diarrhea; Celiac Disease
PubMed: 37345595
DOI: 10.15403/jgld-4624 -
Frontiers in Immunology 2023Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in gene, which encodes a...
INTRODUCTION
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or mutations (Ferre-Lionakis criteria).
PATIENTS AND METHODS
We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms.
RESULTS
Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome.
CONCLUSION
Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.
Topics: Humans; Male; Child; Female; Hepatitis, Autoimmune; Polyendocrinopathies, Autoimmune; Mutation; Italy; Intestinal Diseases
PubMed: 37457714
DOI: 10.3389/fimmu.2023.1172369 -
Revista Espanola de Enfermedades... Jan 2024Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds... (Observational Study)
Observational Study
Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds to a gluten-free diet (GFD) and is sometimes the only manifestation in paucisymptomatic CD. Through this descriptive observational study, we determined the prevalence of liver abnormalities upon diagnosis of CD. A total of 140 patients were included. The prevalence of alterations in liver markers at diagnosis of CD was 47%. In 2.9% of patients, liver abnormalities were the only manifestation at diagnosis. A higher prevalence of liver alterations was found in those patients who presented a more severe histological alteration (MARSH 3c).
Topics: Humans; Celiac Disease; Liver Diseases; Diet, Gluten-Free; Biopsy; Inflammatory Bowel Diseases
PubMed: 37204091
DOI: 10.17235/reed.2023.9516/2023 -
Clinical and Translational... Dec 2023Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD).
INTRODUCTION
Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD).
METHODS
We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi.
RESULTS
Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not.
DISCUSSION
tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.
Topics: Humans; Celiac Disease; Retrospective Studies; Transglutaminases; Biomarkers; Autoantibodies; Immunoglobulin A; Atrophy; Cytokines; Lipoproteins, LDL; Cholesterol
PubMed: 37753949
DOI: 10.14309/ctg.0000000000000639 -
Journal of Clinical Immunology Aug 2023Hyper activation of the JAK-STAT signaling underlies the pathophysiology of many human immune-mediated diseases. Herein, the study of 2 adult patients with SOCS1...
PURPOSE
Hyper activation of the JAK-STAT signaling underlies the pathophysiology of many human immune-mediated diseases. Herein, the study of 2 adult patients with SOCS1 haploinsufficiency illustrates the severe and pleomorphic consequences of its impaired regulation in the intestinal tract.
METHODS
Two unrelated adult patients presented with gastrointestinal manifestations, one with Crohn's disease-like ileo-colic inflammation refractory to anti-TNF and the other with lymphocytic leiomyositis causing severe chronic intestinal pseudo-occlusion. Next-generation sequencing was used to identify the underlying monogenic defect. One patient received anti-IL-12/IL-23 treatment while the other received the JAK1 inhibitor, ruxolitinib. Peripheral blood, intestinal tissues, and serum samples were analyzed before-and-after JAK1 inhibitor therapy using mass cytometry, histology, transcriptomic, and Olink assay.
RESULTS
Novel germline loss-of-function variants in SOCS1 were identified in both patients. The patient with Crohn-like disease achieved clinical remission with anti-IL-12/IL-23 treatment. In the second patient with lymphocytic leiomyositis, ruxolitinib induced rapid resolution of the obstructive symptoms, significant decrease of the CD8+ T lymphocyte muscular infiltrate, and normalization of serum and intestinal cytokines. Decreased frequencies of circulating Treg cells, MAIT cells, and NK cells, with altered CD56:CD16:CD16 NK subtype ratios were not modified by ruxolitinib.
CONCLUSION
SOCS1 haploinsufficiency can result in a broad spectrum of intestinal manifestations and need to be considered as differential diagnosis in cases of severe treatment-refractory enteropathies, including the rare condition of lymphocytic leiomyositis. This provides the rationale for genetic screening and considering JAK inhibitors in such cases.
Topics: Adult; Humans; Haploinsufficiency; Tumor Necrosis Factor Inhibitors; Suppressor of Cytokine Signaling Proteins; Interleukin-12; Interleukin-23; Suppressor of Cytokine Signaling 1 Protein
PubMed: 37156989
DOI: 10.1007/s10875-023-01495-7 -
Iranian Journal of Biotechnology Jul 2023Celiac disease (CD) is a gluten-sensitive chronic autoimmune enteropathy. A strict life-long gluten-free diet is the only efficient and accepted treatment until now....
BACKGROUND
Celiac disease (CD) is a gluten-sensitive chronic autoimmune enteropathy. A strict life-long gluten-free diet is the only efficient and accepted treatment until now. However, maintaining a truly gluten-free status is both difficult and costly, often resulting in a social burden for the person. Moreover, 2 to 5 percent of patients fail to improve clinically and histologically upon elimination of dietary gluten. Therefore, novel therapeutic approaches, including gluten degrading enzymes, are an unmet need of celiac patients.
OBJECTIVES
To evaluate the function of sunn pest prolyl endoprotease for gluten and gliadin hydrolysis in vitro.
MATERIALS AND METHODS
The spPEP was expressed as a recombinant protein in , and its catalytic activity was assessed by SDS-PAGE and RP-HPLC analyses.
RESULTS
Production of a 100-kDa spPEP protein was confirmed by SDS-PAGE and western blot analysis. Also, we demonstrate that spPEP efficiently degrades gluten and α-gliadin (30-40 kDa) in vitro under conditions similar to the GI and is resistant to pepsin and trypsin.
CONCLUSION
The gathered data demonstrated that spPEP might be a novel candidate for Oral Enzymatic Therapy (OET) in CD and other gluten-related disorders.
PubMed: 38344704
DOI: 10.30498/ijb.2023.347693.3420 -
JPGN Reports Feb 2024Autoimmune enteropathy is a rare cause of chronic intractable diarrhea and is present in <1 in 100,000 infants. We report the case of a 9-month-old boy who presented...
Autoimmune enteropathy is a rare cause of chronic intractable diarrhea and is present in <1 in 100,000 infants. We report the case of a 9-month-old boy who presented with intractable diarrhea and vomiting. Genetic panel testing revealed a STAT3 heterozygous mutation in exon 6, suggesting infantile-onset multisystem autoimmune disease-1. The patient was initially treated with steroids and sulfasalazine. However, on tapering steroids, he had another episode of diarrhea and was subsequently put on baricitinib to which he responded.
PubMed: 38545278
DOI: 10.1002/jpr3.12038