Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults p...Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease.Initial diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe immu-nodeficiency.Refined criteria emphasize characteristic histological findings and exclusion of other causes of villous atrophy.AIE is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial lympho-cytosis.Treatment primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional support.Despite the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient outcome.Further research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.展开更多
BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically e...BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.展开更多
BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.Howe...BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.展开更多
BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis an...BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with ...Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.展开更多
This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented int...This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major close-limiting factor. Microvascular injury is a prominent feature of both early （inflammatory）, as well as delayed （fibroproliferative） radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.展开更多
Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological ...Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (α1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4- positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-γ) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.展开更多
Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasing...Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentationand grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed.展开更多
AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obs...AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.展开更多
A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa,and histopathological examination was compatible with collagenous...A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa,and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon,particularly in the ascending portion,was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy (PLE) without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.展开更多
AIM: To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy,59 patients were followed up after 15-18 years. METHODS: Fifty-nine patients were prospectively en...AIM: To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy,59 patients were followed up after 15-18 years. METHODS: Fifty-nine patients were prospectively enrolled by twelve surgical departments. Primary malignant disease,radiation therapy and surgical management were recorded at inclusion. The cause of death or persistence of symptoms was examined in public death records or by interview of survivors. RESULTS: Thirty-nine patients had received radiation therapy for gynaecological cancers,twelve for urological cancers,four for gastrointestinal cancers and four for other malignancies. Forty-five patients (76%) required surgical intervention. Complications occurred in 11 (25%) operated patients. Forty-seven patients had died at the time of follow-up,seven (12%) died as a direct result of radiation enteropathy,while radiation enteropathy contributed to death in an additional seven patients. Four of the twelve surviving patients suffered from chronic debilitating symptoms of radiation enteropathy,while three had moderate symptoms. CONCLUSION: Patients with severe delayed radiation enteropathy have a high risk of persistence of symptoms after surgery. At least one in ten patients dies from radiation-induced bowel injury.展开更多
AIM:To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE).METHODS:This was a single center,non-randomized,open-label,uncontrolled pilot study,usin...AIM:To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE).METHODS:This was a single center,non-randomized,open-label,uncontrolled pilot study,using the PillCam SB CE system with RAPID 5 software.The Lewis Index Score (LIS) for small bowel injury was investigated to evaluate the severity of mucosal injury.Arthropathy patients with at least one month history of daily naproxen use of 1000 mg and proton pump inhibitor co-therapy were screened.Patients with a minimum LIS of 135 were eligible to enter the 4-wk treatment phase of the study.During this treatment period,3 × 1000 mg/d mesalazine granules were added to ongoing therapies of 1000 mg/d naproxen and 20 mg/d omeprazole.At the end of the 4-wk combined treatment period,a second small bowel CE was performed to re-evaluate the enteropathy according to the LIS results.The primary objective of this study was to assess the mucosal changes after 4 wk of mesalazine treatment.RESULTS:A total of 18 patients (16 females),ranging in age from 46 to 78 years (mean age 60.3 years) were screened,all had been taking 1000 mg/d naproxen for at least one month.Eight patients were excluded from the mesalazine therapeutic phase of the study for the following reasons:the screening CE showed normal small bowel mucosa or only insignificant damages (LIS < 135) in five patients,the screening esophagogastroduodenoscopy revealed gastric ulcer in one patient,capsule technical failure and incomplete CE due to poor small bowel cleanliness in two patients.Ten patients (9 female,mean age 56.2 years) whose initial LIS reached mild and moderate-to-severe enteropathy grades (between 135 and 790 and ≥ 790) entered the 4-wk therapeutic phase and a repeat CE was performed.When comparing the change in LIS from baseline to end of treatment in all patients,a marked decrease was seen (mean LIS:1236.4 ± 821.9 vs 925.2 ± 543.4,P=0.271).Moreover,a significant difference between pre-and post-treatment mean total LIS was detected in 7 patients who had moderate-tosevere enteropathy gradings at the inclusion CE (mean LIS:1615 ± 672vs 1064 ± 424,P=0.033).CONCLUSION:According to the small bowel CE evaluation mesalazine granules significantly attenuated mucosal injuries in patients with moderate-to-severe enteropathies induced by naproxen.展开更多
AIM： To evaluate computed tomography （CT） findings, useful to suggest the presence of refractory celiac disease （RCD） and enteropathy associated T cell lymphoma （EATL）. METHODS： Coeliac disease （CD） patients...AIM： To evaluate computed tomography （CT） findings, useful to suggest the presence of refractory celiac disease （RCD） and enteropathy associated T cell lymphoma （EATL）. METHODS： Coeliac disease （CD） patients were divided into two groups. Group Ⅰ ： uncomplicated CD （n = 14） and RCD type Ⅰ （n = 10）. Group Ⅱ ： RCD type Ⅱ （n = 15） and EATL （n = 7）. RESULTS： Both groups showed classic signs of CD on CT. Intussusception was seen in 1 patient in group Ⅰ vs 5 in group Ⅱ （P = 0.06）. Lymphadenopathy was seen in 5 patients in group Ⅱ vs no patients in group Ⅰ （P = 0.01）. Increased number of small mesenteric vessels was noted in 20 patients in group Ⅰ vs Ⅱ in group 11 （P = 0.02）. Eleven patients （50%） in group 11 had a splenic volume 〈 122 cm^3 vs 4 in group Ⅰ （14%）, 10 patients in group Ⅰ had a splenic volume 〉 196 cm^3 （66.7%） vs 5 in group Ⅱ （33.3%） P = 0.028. CONCLUSION： CT scan is a useful tool in discriminating between CD and （Pre） EATL. RCD Ⅱ and EATL showed more bowel wall thickening, lymphadenopathy and intussusception, less increase in number of small mesenteric vessels and a smaller splenic volume compared with CD and RCD Ⅰ.展开更多
Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before ...Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.展开更多
The case of a 22-year-old patient with symptomatic hypokalemia caused by rhabdomyolysis is presented as a rarely reported complication of gluten-sensitive enteropathy (GSE) and dermatitis herpetiformis Duhring. The pa...The case of a 22-year-old patient with symptomatic hypokalemia caused by rhabdomyolysis is presented as a rarely reported complication of gluten-sensitive enteropathy (GSE) and dermatitis herpetiformis Duhring. The patient's myopathy ceased on potassium supplementation and her other complaints resolved while on gluten-free diet.Recovery was otherwise uneventful with a rapid decline in serum CPK level. At the time of her last follow-up a few months later, she was free of symptoms and CPK remained stable. Patients with GSE may present with hypokalemia in association with diarrhea and emesis, and if potassium loss is rapid, rhabdomyolysis may occur.展开更多
BACKGROUND Congenital tufting enteropathy(CTE)is a rare cause of diarrhea in children.However,it can result in early-onset of chronic diarrhea and failure to thrive.Children with this disease have to depend on total p...BACKGROUND Congenital tufting enteropathy(CTE)is a rare cause of diarrhea in children.However,it can result in early-onset of chronic diarrhea and failure to thrive.Children with this disease have to depend on total parenteral nutrition(TPN),and eventually small intestine transplantation.The epithelial cell adhesion molecule(EPCAM)gene was identified to be associated with CTE.Here,we present a case of an infant with CTE due to a mutation not reported in the literature before.CASE SUMMARY A 1-year and 7-mo infant boy exhibited intractable watery diarrhea and mushy stool within 1 wk after birth,for which he had required medical treatment and hospitalization several times.His sister presented similar symptoms and died at the age of two.On admission,his body weight was 5700 g(-4.8 SDS)and measured 66 cm(-5.4 SDS)in height.Meanwhile,he cannot speak or climb.He exhibited mild anemia,hypocalcemia,hypomagnesemia,and an infection in the upper respiratory tract.Microvilli sparse and vacuolar degeneration of epithelial cells were reported by small intestine biopsy.Whole-exome sequencing showed a novel homozygous splice mutation(c.657+1[IVS6]G>A)in the EPCAM gene.He was treated with TPN and recombinant human growth hormone.After 2 mo,his body weight was up to 8500 g and he has been waiting for small bowel transplantation.CONCLUSION CTE is rare but fatal.Patients with CTE require rapid diagnosis and therapy to improve their survival.展开更多
To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODSFibrinogen wild-type (Fib<sup>+/+</sup>), fibrinogen hetero...To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODSFibrinogen wild-type (Fib<sup>+/+</sup>), fibrinogen heterozygous (Fib<sup>+/-</sup>), and fibrinogen knockout (Fib<sup>-/-</sup>) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTSThere was no difference between sham-irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib<sup>+/-</sup> mice were used as littermate controls. Unlike sham-irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib<sup>-/-</sup> mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib<sup>-/-</sup> mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice. Importantly, irradiated Fib<sup>-/-</sup> mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice at both 2 wk and 26 wk. CONCLUSIONThese data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage.展开更多
Gluten-sensitive enteropathy,also known as coeliac disease(CD),is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nu...Gluten-sensitive enteropathy,also known as coeliac disease(CD),is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients.As it is triggered by dietary gluten and related prolamins present in wheat,rye and barley,the accepted treatment for CD is a strict gluten-free diet.However,a complete exclusion of gluten-containing cereals from the diet is often difficult,and new therapeutic strategies are urgently needed.A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins(HSPs),which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors.HSPs are expressed in several tissues,including the gastrointestinal tract,and their levels are significantly increased under stress circumstances.HSPs exert immunomodulatory effects,and also play a crucial role in the maintenance of epithelial cell structure and function,as they are responsible for adequate protein folding,influence the degradation of proteins and cell repair processes after damage,and modulate cell signalling,cell proliferation and apoptosis.The present review discusses the involvement of HSPs in the pathophysiology of CD.Furthermore,HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective,immunomodulatory,and anti-apoptotic effects in the intestinal mucosal barrier.展开更多
BACKGROUND Autoimmune enteropathy(AIE)and primary biliary cholangitis(PBC)are both immune-mediated diseases.AIE or PBC complicated with ulcerative colitis(UC)are rare.There are no cases of AIE and PBC diagnosed after ...BACKGROUND Autoimmune enteropathy(AIE)and primary biliary cholangitis(PBC)are both immune-mediated diseases.AIE or PBC complicated with ulcerative colitis(UC)are rare.There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before,and the pathogenesis of these comorbidities has not been revealed.CASE SUMMARY A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease,and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016.A few months after the neoileostomy,she began to suffer from recurrent episodes of watery diarrhea.She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect.However,her symptoms of diarrhea relapsed in 2019,with different histological features of endoscopic biopsies compared with 2016,which showed apoptotic bodies,a lack of goblet and Paneth cells,and villous blunting.A diagnosis of AIE was established,and the patient’s stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d.Meanwhile,her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC,and treatment with ursodeoxycholic acid(16 mg/kg per day)achieved satisfactory results.CONCLUSION Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients.Continuous follow-up is essential for UC patients with postoperative complications.展开更多
文摘Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease.Initial diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe immu-nodeficiency.Refined criteria emphasize characteristic histological findings and exclusion of other causes of villous atrophy.AIE is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial lympho-cytosis.Treatment primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional support.Despite the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient outcome.Further research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-132.
文摘BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.
基金Supported by the Shandong Provincial Natural Science Foundation of China,No.ZR2023QH015Qingdao Municipal Natural Science Foundation of China,No.23-2-1-134-zyyd-jch.
文摘BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022 and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.2021-1-I2M-003+1 种基金Undergraduate Innovation Program,No.2023-zglc-06034National Key Clinical Specialty Construction Project,No.ZK108000。
文摘BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
基金Supported by The European Union-NextGenerationEU,Through The National Recov-ery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
基金National Institutes of Health, Grant CA83719US Department of Veterans Affairs
文摘This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major close-limiting factor. Microvascular injury is a prominent feature of both early （inflammatory）, as well as delayed （fibroproliferative） radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.
文摘Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (α1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4- positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-γ) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.
文摘Portal hypertensive enteropathy(PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentationand grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed.
基金Supported by Local funds from Digestive Disease Research Centre, University of Tehran and Gastrointestinal and Liver Disease Research Centre, Iran University of Medical Science
文摘AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.
文摘A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa,and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon,particularly in the ascending portion,was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy (PLE) without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.
文摘AIM: To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy,59 patients were followed up after 15-18 years. METHODS: Fifty-nine patients were prospectively enrolled by twelve surgical departments. Primary malignant disease,radiation therapy and surgical management were recorded at inclusion. The cause of death or persistence of symptoms was examined in public death records or by interview of survivors. RESULTS: Thirty-nine patients had received radiation therapy for gynaecological cancers,twelve for urological cancers,four for gastrointestinal cancers and four for other malignancies. Forty-five patients (76%) required surgical intervention. Complications occurred in 11 (25%) operated patients. Forty-seven patients had died at the time of follow-up,seven (12%) died as a direct result of radiation enteropathy,while radiation enteropathy contributed to death in an additional seven patients. Four of the twelve surviving patients suffered from chronic debilitating symptoms of radiation enteropathy,while three had moderate symptoms. CONCLUSION: Patients with severe delayed radiation enteropathy have a high risk of persistence of symptoms after surgery. At least one in ten patients dies from radiation-induced bowel injury.
基金Supported by Dr.Falk Pharma GmbH,in part,study code:SAG-43/SBE
文摘AIM:To investigate the effect of mesalazine granules on small intestinal injury induced by naproxen using capsule endoscopy (CE).METHODS:This was a single center,non-randomized,open-label,uncontrolled pilot study,using the PillCam SB CE system with RAPID 5 software.The Lewis Index Score (LIS) for small bowel injury was investigated to evaluate the severity of mucosal injury.Arthropathy patients with at least one month history of daily naproxen use of 1000 mg and proton pump inhibitor co-therapy were screened.Patients with a minimum LIS of 135 were eligible to enter the 4-wk treatment phase of the study.During this treatment period,3 × 1000 mg/d mesalazine granules were added to ongoing therapies of 1000 mg/d naproxen and 20 mg/d omeprazole.At the end of the 4-wk combined treatment period,a second small bowel CE was performed to re-evaluate the enteropathy according to the LIS results.The primary objective of this study was to assess the mucosal changes after 4 wk of mesalazine treatment.RESULTS:A total of 18 patients (16 females),ranging in age from 46 to 78 years (mean age 60.3 years) were screened,all had been taking 1000 mg/d naproxen for at least one month.Eight patients were excluded from the mesalazine therapeutic phase of the study for the following reasons:the screening CE showed normal small bowel mucosa or only insignificant damages (LIS < 135) in five patients,the screening esophagogastroduodenoscopy revealed gastric ulcer in one patient,capsule technical failure and incomplete CE due to poor small bowel cleanliness in two patients.Ten patients (9 female,mean age 56.2 years) whose initial LIS reached mild and moderate-to-severe enteropathy grades (between 135 and 790 and ≥ 790) entered the 4-wk therapeutic phase and a repeat CE was performed.When comparing the change in LIS from baseline to end of treatment in all patients,a marked decrease was seen (mean LIS:1236.4 ± 821.9 vs 925.2 ± 543.4,P=0.271).Moreover,a significant difference between pre-and post-treatment mean total LIS was detected in 7 patients who had moderate-tosevere enteropathy gradings at the inclusion CE (mean LIS:1615 ± 672vs 1064 ± 424,P=0.033).CONCLUSION:According to the small bowel CE evaluation mesalazine granules significantly attenuated mucosal injuries in patients with moderate-to-severe enteropathies induced by naproxen.
文摘AIM： To evaluate computed tomography （CT） findings, useful to suggest the presence of refractory celiac disease （RCD） and enteropathy associated T cell lymphoma （EATL）. METHODS： Coeliac disease （CD） patients were divided into two groups. Group Ⅰ ： uncomplicated CD （n = 14） and RCD type Ⅰ （n = 10）. Group Ⅱ ： RCD type Ⅱ （n = 15） and EATL （n = 7）. RESULTS： Both groups showed classic signs of CD on CT. Intussusception was seen in 1 patient in group Ⅰ vs 5 in group Ⅱ （P = 0.06）. Lymphadenopathy was seen in 5 patients in group Ⅱ vs no patients in group Ⅰ （P = 0.01）. Increased number of small mesenteric vessels was noted in 20 patients in group Ⅰ vs Ⅱ in group 11 （P = 0.02）. Eleven patients （50%） in group 11 had a splenic volume 〈 122 cm^3 vs 4 in group Ⅰ （14%）, 10 patients in group Ⅰ had a splenic volume 〉 196 cm^3 （66.7%） vs 5 in group Ⅱ （33.3%） P = 0.028. CONCLUSION： CT scan is a useful tool in discriminating between CD and （Pre） EATL. RCD Ⅱ and EATL showed more bowel wall thickening, lymphadenopathy and intussusception, less increase in number of small mesenteric vessels and a smaller splenic volume compared with CD and RCD Ⅰ.
文摘Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.
文摘The case of a 22-year-old patient with symptomatic hypokalemia caused by rhabdomyolysis is presented as a rarely reported complication of gluten-sensitive enteropathy (GSE) and dermatitis herpetiformis Duhring. The patient's myopathy ceased on potassium supplementation and her other complaints resolved while on gluten-free diet.Recovery was otherwise uneventful with a rapid decline in serum CPK level. At the time of her last follow-up a few months later, she was free of symptoms and CPK remained stable. Patients with GSE may present with hypokalemia in association with diarrhea and emesis, and if potassium loss is rapid, rhabdomyolysis may occur.
基金Key Research and Development Program of Zhejiang Province,China,No.2020C03121。
文摘BACKGROUND Congenital tufting enteropathy(CTE)is a rare cause of diarrhea in children.However,it can result in early-onset of chronic diarrhea and failure to thrive.Children with this disease have to depend on total parenteral nutrition(TPN),and eventually small intestine transplantation.The epithelial cell adhesion molecule(EPCAM)gene was identified to be associated with CTE.Here,we present a case of an infant with CTE due to a mutation not reported in the literature before.CASE SUMMARY A 1-year and 7-mo infant boy exhibited intractable watery diarrhea and mushy stool within 1 wk after birth,for which he had required medical treatment and hospitalization several times.His sister presented similar symptoms and died at the age of two.On admission,his body weight was 5700 g(-4.8 SDS)and measured 66 cm(-5.4 SDS)in height.Meanwhile,he cannot speak or climb.He exhibited mild anemia,hypocalcemia,hypomagnesemia,and an infection in the upper respiratory tract.Microvilli sparse and vacuolar degeneration of epithelial cells were reported by small intestine biopsy.Whole-exome sequencing showed a novel homozygous splice mutation(c.657+1[IVS6]G>A)in the EPCAM gene.He was treated with TPN and recombinant human growth hormone.After 2 mo,his body weight was up to 8500 g and he has been waiting for small bowel transplantation.CONCLUSION CTE is rare but fatal.Patients with CTE require rapid diagnosis and therapy to improve their survival.
基金Supported by Arkansas Space Grant Consortium and National Space Biomedical Research Institute through National Aeronautics and Space Administration,No.NNX15AK32A(RP)and No.RE03701(MH-J)National Institutes of Health,No.P20 GM109005(MH-J)
文摘To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODSFibrinogen wild-type (Fib<sup>+/+</sup>), fibrinogen heterozygous (Fib<sup>+/-</sup>), and fibrinogen knockout (Fib<sup>-/-</sup>) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTSThere was no difference between sham-irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib<sup>+/-</sup> mice were used as littermate controls. Unlike sham-irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib<sup>-/-</sup> mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib<sup>-/-</sup> mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice. Importantly, irradiated Fib<sup>-/-</sup> mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib<sup>+/+</sup> and Fib<sup>+/-</sup> mice at both 2 wk and 26 wk. CONCLUSIONThese data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target in treating intestinal damage.
基金Supported by OTKA-84087/2010,-K81117,-K105530,-PD83431,-PD105361,"Lendulet"Research Grant LP2011-008,2011 and KMR_12-1-2012-0074Vannayáand Veres G are holders of the János Bolyai Research Grant by János Bolyai Research Scholarship of the Hungarian Academy of Sciences
文摘Gluten-sensitive enteropathy,also known as coeliac disease(CD),is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients.As it is triggered by dietary gluten and related prolamins present in wheat,rye and barley,the accepted treatment for CD is a strict gluten-free diet.However,a complete exclusion of gluten-containing cereals from the diet is often difficult,and new therapeutic strategies are urgently needed.A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins(HSPs),which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors.HSPs are expressed in several tissues,including the gastrointestinal tract,and their levels are significantly increased under stress circumstances.HSPs exert immunomodulatory effects,and also play a crucial role in the maintenance of epithelial cell structure and function,as they are responsible for adequate protein folding,influence the degradation of proteins and cell repair processes after damage,and modulate cell signalling,cell proliferation and apoptosis.The present review discusses the involvement of HSPs in the pathophysiology of CD.Furthermore,HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective,immunomodulatory,and anti-apoptotic effects in the intestinal mucosal barrier.
基金Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),No.2017-I2M-3-017.
文摘BACKGROUND Autoimmune enteropathy(AIE)and primary biliary cholangitis(PBC)are both immune-mediated diseases.AIE or PBC complicated with ulcerative colitis(UC)are rare.There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before,and the pathogenesis of these comorbidities has not been revealed.CASE SUMMARY A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease,and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016.A few months after the neoileostomy,she began to suffer from recurrent episodes of watery diarrhea.She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect.However,her symptoms of diarrhea relapsed in 2019,with different histological features of endoscopic biopsies compared with 2016,which showed apoptotic bodies,a lack of goblet and Paneth cells,and villous blunting.A diagnosis of AIE was established,and the patient’s stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d.Meanwhile,her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC,and treatment with ursodeoxycholic acid(16 mg/kg per day)achieved satisfactory results.CONCLUSION Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients.Continuous follow-up is essential for UC patients with postoperative complications.
