Diagnosis Of Protein-losing Enteropathy Research Articles

Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome

Introduction: Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation. Hypothesis: We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation. Methods: This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites. Results: Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period. Conclusions: Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation. Key words: Camostat mesylate; protein-losing enteropathy; Fontan operation Source of Funding: This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.

Constrictive Pericarditis and Protein-Losing Enteropathies: Exploring the Heart-Gut Axis.

Background/Objectives: Constrictive pericarditis very rarely causes protein-losing enteropathy (PLE) induced by secondary intestinal lymphangiectasia. This study thoroughly reviewed the literature to shed light on the clinical management of PLE provoked by intestinal lymphangiectasia following constrictive pericarditis. Methods: We performed a PubMed search using the keywords enteropathy, protein-losing enteropathy, pericarditis, acute pericarditis, pericardial effusion, recurrent pericarditis, constrictive pericarditis, noninfectious pericarditis, idiopathic pericarditis, and infective pericarditis, with only English-language publications included. Results: Although constrictive pericarditis is primarily idiopathic, less common causes include infectious etiologies, connective/autoimmune tissue disorders, previous cardiac surgery, congenital syndromes, and cancer. On the one hand, PLE secondary to intestinal lymphangiectasia may cause a severe cellular immune deficiency that could raise infection hazards due to lymphocytopenia and hypogammaglobulinemia. On the other hand, lymphocytopenia may cause anergy and mask an underlying tuberculous etiology of constrictive pericarditis. Cardiac catheterization is the most useful diagnostic tool for constrictive pericarditis, though it may be misdiagnosed in rare cases. The videocapsule endoscopy and double-balloon enteroscopy techniques can detect small bowel lymphangiectasias distal to the Treitz ligament. MRI or a CT scan helps confirm constrictive pericarditis, visualize lymphangiectasias, and reveal features specific to the underlying etiology of PLE. Radioisotopic techniques may ensure PLE diagnosis in challenging cases, whereas fecal alpha1-antitrypsin can estimate gastrointestinal protein loss. Conclusions: Constrictive pericarditis is rarely associated with PLE. The cardio-intestinal abnormalities of PLE caused by constrictive pericarditis are frequently reversed following a complete pericardiectomy, though its ability to invert severe hypoalbuminemia is currently unknown.

Protein-Losing Enteropathy after Fontan Operation: A Clinical Case Description

The clinical observation of a boy with protein-losing enteropathy after the Fontan operation is presented. The boy, S.M., 2 years old, was admitted with complaints of abdominal pain, bloating, enlarged abdomen, frequent watery stools, and peripheral edema in the arms and legs. The child was diagnosed with a congenital heart defect at birth, for which Fontan surgery was performed. One month later, diarrhea and swelling appeared on the face, arms, and legs. Edema was temporarily relieved by symptomatic therapy. At the age of 2, the child was hospitalized in the gastroenterology department of our center. Examinations revealed low levels of total protein and albumin, and an increase in alpha-1 antitrypsin values. The diagnosis of protein-losing enteropathy after the Fontan operation was established. The child was prescribed a diet enriched with medium-chain triglycerides, spironolactone, and prednisolone. After 6 months of follow-up, no edema was observed, and the child’s overall condition was satisfactory. However, over the past year until the present, the boy has experienced slight swelling in the arms, legs, and face, requiring periodic albumin transfusions. Fontan operation and protein-losing enteropathy represent different aspects of medicine; however, sometimes one diagnosis becomes a consequence of another. As a collective of authors, we conducted the research, processed the data, obtained results, and we believe that we are correct. We affirm that the responsibility for the results and activity in writing the material remains with the authors.

The impact of the COVID-19 pandemic on individuals with Fontan circulation: Focus on gaps in care

BackgroundGaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors. MethodsThis retrospective study evaluated individuals with Fontan circulation followed at our center since 2010. A gap in care was defined as an absence of any formal cardiology provider-patient contact (clinic visit or telehealth) for >15 months. ResultsOver a third of 308 patients with Fontan circulation experienced at least one gap in care between 2010 and 2022, and 77 experienced a gap in care during the COVID-19 pandemic. Of this latter group, 27 (35%) had never experienced a prior gap in cardiology care until the pandemic. Those who experienced gaps in care during the pandemic were on average older (18.0 [IQR 9.6–25.6] vs. 14.2 [7.2–21.2] years, p = 0.01), more likely to be of Black/African American race (23.4% vs 7.4%, p = 0.001), and less likely to have a diagnosis of protein-losing enteropathy or plastic bronchitis (0% vs. 8.6%, p = 0.005). Those without a gap in care during the pandemic were more likely to have utilized telehealth visits (13% vs 3%, p = 0.02). ConclusionGaps in care are common and appear to have been exacerbated by the COVID-19 pandemic in those with a Fontan circulation. Such gaps are particularly common among African American and adult patients, and may potentially be mitigated by expanding telehealth access.

S3415 Gastroenterological Manifestations in a Patient With Common Variable Immunodeficiency

Introduction: Gastrointestinal manifestation of common variable immunodeficiency (CVID) can present with protein-losing enteropathy (PLE). A wide spectrum of liver injuries can occur with CVID, including nodular regenerative hyperplasia (NRH). Case Description/Methods: 41 y.o. female with PMH of CVID on IgG, chronically elevated LFTs, and nutritional deficiencies. Patient presented with 8-year history of diarrhea, bloating, weight loss, abdominal pain, hepatic encephalopathy (HE), new ascites, and shock. Previously was diagnosed with celiac disease and has strictly followed a gluten-free diet with no improvement. EGD on the current presentation showed visible changes in duodenal mucosa including villous flattening. Biopsies this time revealed villous flattening and absence of plasma cells consistent with CVID enteropathy. Liver biopsy 5 years prior to admission showed no liver disease. Serologic workups, including anti-gp210 and anti-sp100, were negative. Biopsy showed nodular regenerative hyperplasia and non-cirrhotic portal hypertension, which was confirmed by reticulin stain. Patient was started on budesonide 9 mg daily for treatment of PLE, and marked improvement of diarrhea was noted. Non-cirrhotic portal hypertension was managed with furosemide and spironolactone. HE was managed with oral lactulose. The patient was started on enteral and parenteral supplements. Discussion: Duodenal villous atrophy which is a diagnostic criterion for celiac disease can be seen in multiple other conditions including immune disorders such as CVID. In CVID patients with gastrointestinal symptoms, up to 80% of biopsies from different sites in the GI tract will show histological abnormalities. Given their common presentation, celiac disease can be initially diagnosed. The absence of plasma cells and apoptosis presence in duodenal biopsy can suggest PLE diagnosis. Serological studies are not reliable for celiac disease diagnosis due to deficiency of immunoglobulin production in CVID. Steroids can be used for the treatment of PLE in CVID. Hepatic manifestations in CVID are extremely varied and often misdiagnosed given they can mimic other diseases. NRH is a potentially fatal complication of CVID. Recognition of this complication allowed for symptom resolution within two days of starting lactulose therapy. NRH in CVID represents an autoimmune-like liver disease that might be driven by a local vasculopathy, and thus severe cases can warrant a trial of immunosuppression.

Anesthetic Management in Parturients With Fontan Physiology

Anesthetic Management in Parturients With Fontan Physiology

Long-term Outcome of Fontan-Associated Protein-Losing Enteropathy: Treatment Modality and Predictive Factor of Mortality.

Protein-losing enteropathy (PLE) is a devastating complication after the Fontan operation. This study aimed to investigate the clinical characteristics, treatment response, and outcomes of Fontan-associated PLE. We reviewed the medical records of 38 patients with Fontan-associated PLE from 1992 to 2018 in 2 institutions in Korea. PLE occurred in 4.6% of the total 832 patients after the Fontan operation. After a mean period of 7.7 years after Fontan operation, PLE was diagnosed at a mean age of 11.6 years. The mean follow-up period was 8.9 years. The survival rates were 81.6% at 5 years and 76.5% at 10 years. In the multivariate analysis, New York Heart Association Functional classification III or IV (p=0.002), low aortic oxygen saturation (<90%) (p=0.003), and ventricular dysfunction (p=0.032) at the time of PLE diagnosis were found as predictors of mortality. PLE was resolved in 10 of the 38 patients after treatment. Among medical managements, an initial heparin response was associated with survival (p=0.043). Heparin treatment resulted in resolution in 4 patients. We found no evidence on pulmonary vasodilator therapy alone. PLE was also resolved after surgical Fontan fenestration (2/6), aortopulmonary collateral ligation (1/1), and transplantation (1/1). The survival rate of patients with Fontan-associated PLE has improved with the advancement of conservative care. Although there is no definitive method, some treatments led to the resolution of PLE in one-fourth of the patients. Further investigations are needed to develop the best prevention and therapeutic strategies for PLE.

A193 DGAT1 DEFICIENCY WITHOUT DIARRHEA

Abstract Background Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis and is highly expressed in enterocytes (EC). DGAT1 deficiency (DGAT1D) is a rare autosomal recessive protein losing enteropathy (PLE) classified as a congenital diarrheal disorder (CDD). Presumably, fat ingestion causes accumulation of DGAT1 substrates within the EC causing lipotoxicity-induced EC dysfunction and death. Aims Report a presentation of DGAT1D atypical for a CDD. Methods We present an infant with DGAT1D with protracted emesis and failure to thrive (FTT) in the absence of diarrhea despite enteral nutrition with varied fat containing formulas (FCF). Results A male infant presented with emesis and FTT requiring multiple admissions. He was initially diagnosed with cow’s milk protein allergy due to concurrent bloody stools, which resolved with hypoallergenic formula. Reportedly watery stools when exclusively breastfed became formed following switch to formula at 2 weeks of age. Interestingly, he subsequently required intermittent suppositories. However, emesis and malnutrition progressed, refractory to omeprazole, baclofen, and varied hypo- and non-allergenic FCF (all containing &amp;gt;0.02g/ml fat, mixtures of medium and long chain FA). He had persistently low serum albumin, ceruloplasmin, and IgG, but SA1AT was normal. TGs were normal, although not measured on FCF. Low fecal elastase (FE) normalized after nutritional support but sweat chloride was intermediate. CFTR sequencing revealed CFTR mutations S466X and R1070 in cis. TPN was started for severe malnutrition at 2 months. Emesis resolved while fasted or receiving enteral electrolyte solution. Endoscopic biopsies on FCF showed increased lamina propria cellularity, no villous abnormalities in the duodenum, chronic inflammation in the gastric body, and normal colonic mucosa. Whole exome sequencing at 2 months showed homozygous c.838C&amp;gt;T (p.Arg280Ter) mutations in DGAT1, explaining his clinical presentation and biochemical features of PLE. After diagnosis, he was started on Tolerex® formula (fat = 0.017g/ml), which was tolerated. Conclusions DGAT1D is classified as a CDD, with vomiting often reported. This case describes a unique presentation of this rare condition, with emesis the predominant symptom, and notable constipation, demonstrating the variable phenotype of this condition. Fat malabsorption may contribute to constipation by altering viscosity of luminal contents or activating the ileal brake. Thus, DGAT1D should be considered on the differential for congenital PLE, even without diarrhea. This case also demonstrates the limitations of stool testing in DGAT1D as random SA1AT concentrations may not reflect A1AT clearance in the diagnosis of PLE. Low FE has been detected in children with malnutrition or dietary restriction and has been reported in DGAT1D, where it likely represents a physiologic consequence of FTT. Funding Agencies None

Patients with Fontan circulation beyond the fourth decade of life

Abstract Background The survival rate after Fontan procedure is improving and many of these patients now survive well into adulthood. Data on the late morbidity and mortality of Fontan patients in their fourth decade of life are lacking. Purpose To evaluate the late outcome of adult patients with Fontan circulation who have survived beyond 35 years. Methods Data were collected retrospectively on consecutive patients with a Fontan circulation ≥35 years between 2005 and 2019. Baseline (at 35th birthday) and follow-up data includes functional class, blood tests, history of arrhythmia, heart failure (HF), thromboembolism, Fontan related liver disease (FLD), protein losing enteropathy (PLE) and plastic bronchitis. Echocardiographic data on systemic atrioventricular valve (SAVV) regurgitation and ventricular function were also analysed. Results 61 patients were included (29, 47.5% female). Tricuspid atresia was the most common underline anatomy (29,47.5%) and the median age at Fontan procedure was 12 [8.0–19.0] years. 34 (56%) patients had an atrio-pulmonary connection Fontan and 15 (24.5%) total cavo-pulmonary connection (86.7% lateral tunnel and 13.3% extra-cardiac conduit), 10 (16%) a Bjork Fontan and 2 (3%) a Kawashima procedure. At baseline 40 (66%) patients were in NYHA class II or III, 7 (11%) had a moderate or severely impaired ventricular function and 12 (20%) had at least moderate SSAV regurgitation. At baseline, 35 (57.4%) patients had experienced at least one arrhythmia, 7 (11.4%) patients had a history of atrial thrombosis or thromboembolic events and 2 (3.3%) of PLE. At a median follow-up of 6.4 [2.9–11.3] years, 11 (18%) patients died, 7 of chronic HF, 1 hepatic carcinoma, 1 sepsis, 1 pulmonary embolism, 1 malignancy (1 cause unknown). During follow-up, 28 (46%) patients had a new episode of atrial arrhythmia, 23 (38%) developed FLD and 2 (3.3%) PLE. 9 (15%) required at least one admission for HF. 2 (3.3%) patients experienced worsening of their ventricular function and 7 (11.4%) of their SAVV regurgitation. On univariable analysis, a baseline diagnosis of PLE (HR 15.23, 95% CI:2.77–83.86, p=0.002), HF (HR 6.18, 95% CI:1.74–21.99, p=0.005), atrial arrhythmia (HR 4.99, 95% CI:1.07–23.21, p=0.04), lower serum albumin (HR 1.14, 95% CI:1.06–1.23, p=0.0006), lower iron levels (HR 1.31, 95% CI:1.02–1.68, p=0.04) and a higher urea (HR 1.18, 95% CI:1.04–1.34, p=0.01) were associated with death or heart transplantation. On bivariable analysis, lower serum albumin was stronger than all other univariable predictors. Conclusions Adult Fontan survivors are a high risk population with significant morbidity and mortality driven primarily by HF and other long-term complications of the Fontan operation. The predictors of outcome in this cohort reflects the chronic low cardiac output state and systemic venous hypertension. Vigilance is required to identify patients who may benefit of haemodynamic optimization and close monitoring for Fontan-related complications. Funding Acknowledgement Type of funding source: None

Hypovitaminosis D is associated with negative outcome in dogs with protein losing enteropathy: a retrospective study of 43 cases

BackgroundHypovitaminosis D has previously been shown to be prevalent amongst dogs with protein losing enteropathy (PLE).The hypothesis of this study was that Low 25-hydroxyvitamin D (25(OH) D) serum concentrations could be a risk factor for negative outcome in dogs with PLE.Forty-three dogs diagnosed with PLE (2005–2014) and which serum Vitamin D serum concentrations were collected and archived at −80 Degrees C were analyzed.Post-diagnostic communication with referring veterinarians was made to determine outcome of PLE dogss: Dogs which died due to PLE within 4 months after diagnosis (negative outcome group, n = 22) and dogs alive or which died due to another disease at the end point of the study (1 year after diagnosis, good outcome group, n = 21). Serum samples taken at the time of diagnosis were analysed for ionized calcium (iCa) concentrations and serum 25(OH) D concentration.ResultsClinical (CCECAI) scores, age at PLE diagnosis, and iCa concentrations were not significantly different between dog groups. A significantly greater (p < 0.001) number of PLE dogs treated with hydrolyzed or elimination diet alone showed good outcome as compared to the PLE negative outcome group. Median serum 25(OH) D concentration was significantly (p = 0.017) lower in dogs with negative outcome versus PLE dogs with good outcome. Using logistic regression analysis, 25(OH) D serum concentration was shown to be a statistically significant factor for outcome determination. Cox regression analysis yielded a hazard ratio of 0.974 (95% CI 0.949, 0.999) per each one nmol/l increase in serum 25(OH) D concentration.ConclusionsLow serum 25(OH) D concentration in PLE dogs was significantly associated with poor outcome. Further studies are required to investigate the clinical efficacy of Vitamin D (cholecalciferol) as a potential therapeutic agent for dogs with PLE.

Protein-losing enteropathy

Protein-losing enteropathy (PLE) is a rare complication of intestinal diseases. Its main manifestation is hypoproteinemic edema. The diagnosis of PLE is based on the verification of protein loss into the intestinal lumen, by determining fecal α1-antitrypsin concentration and clearance. The localization of the affected colonic segment is clarified using radiologic and endoscopic techniques. The mainstay of treatment for PLE is a fat-free diet enriched with medium-chain triglycerides. Surgical resection of the affected segment of the colon may be the treatment of choice for severe hypoproteinemia resistant to drug therapy.

Protein-losing Enteropathy in Association with Right Heart Failure

A 65-year-old woman, with past history of mitral valve replacement, developed severe right heart failure. In addition to elevated right heart pressure, she had significant hypoalbuminemia as the important cause of refractory edema. Technetium-99m-labelled human serum albumin scintigraphy showed leak of protein from the transverse colon and the excretion of alpha 1 antitrypsin in the stool was markedly increased. Diagnosis of protein losing enteropathy was established. The etiology was increased lymphatic pressure secondary to right heart failure of multifactorial cause, including elevated left side filling pressures and out of proportion pulmonary hypertension due to old tuberculosis, resulting in significant tricuspid regurgitation. The patient was managed conservatively with increased dose of furosemide from 10-20mg every other day up to 40-60mg/day, and maximum dose of tolvaptan (a vasopressin 2 receptor blocker) of 15mg/ day, in addition to high protein diet.

Performance Evaluation of an ELISA for the Quantitative Measurement of α1-Antitrypsin in Stool.

The diagnosis of protein-losing enteropathy is aided by the measurement of α1-antitrypsin (A1A) in stool and serum to calculate A1A clearance. The objective of this study was to determine the performance characteristics of an ELISA for the measurement of A1A in stool and to determine reference limits for stool A1A and A1A clearance. A1A in stool was measured with a polyclonal antibody-based ELISA. Assay imprecision, analytical sensitivity, linearity, accuracy, analyte stability, and reference intervals were determined. Within-run and total CVs were 5.4% and 6.5% and 13.8% and 14.5% at 17.3 and 66.9 ng/mL, respectively. The limit of quantification was 2.0 ng/mL, and the assay was linear to 85 ng/mL. Mean recovery of A1A added to samples was 108.2%. A1A was stable in stool for a minimum of 2 days, 7 days, and 3 months at room temperature, 4-8 °C and -20 °C, respectively. The upper 95th percentile reference limits for A1A in stool and A1A clearance were 0.48 mg/g and 49 mL/day, respectively. The A1A ELISA demonstrates acceptable performance for quantifying A1A in stool. The assay can be used in conjunction with serum A1A measurements for determining A1A clearance.

40-Year Follow-Up After the Fontan Operation: Long-Term Outcomes of 1,052 Patients

BackgroundThere are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation. ObjectivesThis study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic. MethodsRecords of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study. ResultsOverall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively. ConclusionsAs the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges.

Fontan-Associated Protein-Losing Enteropathy and Plastic Bronchitis

To characterize the medical history, disease progression, and treatment of current-era patients with the rare diseases Fontan-associated protein-losing enteropathy (PLE) and plastic bronchitis. A novel survey that queried demographics, medical details, and treatment information was piloted and placed online via a Facebook portal, allowing social media to power the study. Participation regardless of PLE or plastic bronchitis diagnosis was allowed. Case control analyses compared patients with PLE and plastic bronchitis with uncomplicated control patients receiving the Fontan procedure. The survey was completed by 671 subjects, including 76 with PLE, 46 with plastic bronchitis, and 7 with both. Median PLE diagnosis was 2.5 years post-Fontan. Hospitalization for PLE occurred in 71% with 41% hospitalized ≥ 3 times. Therapy varied significantly. Patients with PLE more commonly had hypoplastic left ventricle (62% vs 44% control; OR 2.81, 95% CI 1.43-5.53), chylothorax (66% vs 41%; OR 2.96, CI 1.65-5.31), and cardiothoracic surgery in addition to staged palliation (17% vs 5%; OR 4.27, CI 1.63-11.20). Median plastic bronchitis diagnosis was 2 years post-Fontan. Hospitalization for plastic bronchitis occurred in 91% with 61% hospitalized ≥ 3 times. Therapy was very diverse. Patients with plastic bronchitis more commonly had chylothorax at any surgery (72% vs 51%; OR 2.47, CI 1.20-5.08) and seasonal allergies (52% vs 36%; OR 1.98, CI 1.01-3.89). Patient-specific factors are associated with diagnoses of PLE or plastic bronchitis. Treatment strategies are diverse without clear patterns. These results provide a foundation upon which to design future therapeutic studies and identify a clear need for forming consensus approaches to treatment.

Gastro-entéropathies exsudatives

Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation.

Clinical Outcomes and Improved Survival in Patients With Protein-Losing Enteropathy After the Fontan Operation

BackgroundPatients with protein-losing enteropathy (PLE) following the Fontan operation have a reported 50% mortality at 5 years after diagnosis. ObjectivesThe aim of this study was to review outcomes in patients with PLE following the Fontan operation. MethodsFrom 1992 to 2010, 42 patients (55% male) with PLE following the Fontan operation were identified from clinical databases at the Mayo Clinic. Data were collected retrospectively. ResultsMean age at PLE diagnosis was 18.9 ± 11.0 years. Initial Fontan operation was performed at 10.1 ± 10.8 years of age. Mean time from Fontan operation to PLE diagnosis was 8.4 ± 14.2 years. Survival was 88% at 5 years. Decreased survival was seen in patients with high Fontan pressure (mean >15 mm Hg; p = 0.04), decreased ventricular function (ejection fraction <55%; p = 0.03), and New York Heart Association functional class >2 at diagnosis (p = 0.04). Patients who died had higher pulmonary vascular resistance (3.8 ± 1.6 Wood units [WU] vs. 2.1 ± 1.1 WU; p = 0.017), lower cardiac index (1.6 ± 0.4 l/min/m2 vs. 2.7 ± 0.7 l/min/m2; p < 0.0001), and lower mixed venous saturation (53% vs. 66%; p = 0.01), compared with survivors. Factors were assessed at the time of PLE diagnosis. Treatments used more frequently in survivors with PLE included spironolactone (21 [68%]), octreotide (7 [21%]), sildenafil (6 [19%]), fenestration creation (15 [48%]), and relief of Fontan obstruction (7 [23%]). ConclusionsPLE remains difficult to treat; however, in the current era, survival has improved with advances in treatment. Further study is needed to better understand the mechanism of disease and ideal treatment strategy.

Anazarka Tarzı Ödem ile Başvuran İki̇ Sütçocuğu: Protei̇n Kaybetti̇ren Enteropati̇

Protein-losing enteropathy (PLE) is characterized by the development of hypoproteinemia and the loss of serum proteins from the gastrointestinal system. It can be complicated with edema, acid, malnutrition, and pleural and pericardial effusion. PLE is rare but has many causes. The reasons can be grouped as erosive and non-erosive gastrointestinal diseases, diseases characterized by central venous pressure increase, and diseases characterized by the development of mesenteric lymphatic obstruction. A PLE diagnosis should be made for the patient who presents with hypoproteinemia after excluding other disorders causing malnutrition, proteinuria and impaired protein synthesis. Treatment consists of a supportive treatment that includes dietary modifi cation. This paper presents two infants who developed anasarca-type edema following different causes and were diagnosed with protein-losing enteropathy due to different etiologies.

Clinical Features, Intestinal Histopathology, and Outcome in Protein‐Losing Enteropathy in Yorkshire Terrier Dogs

BackgroundA poorly understood protein‐losing enteropathy (PLE) disorder has been reported in Yorkshire Terrier dogs.ObjectivesTo describe clinical features, intestinal histopathology, and outcome in Yorkshire Terrier dogs with PLE, and to identify variables predictive of outcome.AnimalsThirty client‐owned Yorkshire Terrier dogs with PLE.MethodsRetrospective study. Records of dogs with a diagnosis of PLE were reviewed. Intestinal histopathology was interpreted using the World Small Animal Veterinary Association gastrointestinal histopathology classification system. Discriminate analysis techniques were used to identify variables predictive of outcome.ResultsFemales outnumbered males (20/30). Median age was 7 years (range 1–12). Common clinical signs were diarrhea (20/30), vomiting (11), ascites and abdominal distension (11), and respiratory difficulty (8). Histopathologic abnormalities included villous lymphatic dilatation, crypt lesions, villous stunting, and variable increases in cellularity of the lamina propria. All dogs were treated with glucocorticoids. Of 23 dogs with long‐term follow‐up, 9 had complete, and 3 had partial, resolution of signs, and 11 failed to respond to treatment. Median survival of responders was 44 months and of nonresponders was 12 months, with 4 dogs experiencing peracute death. Vomiting, monocytosis, severity of hypoalbuminemia, low blood urea nitrogen concentration, and villous blunting were predictive of survival <4 months.ConclusionsIn addition to classic GI signs, Yorkshire Terriers with PLE often show clinical signs associated with hypoalbuminemia and low oncotic pressure. Lymphatic dilatation, crypt lesions, and villous stunting are consistent histopathologic findings. Clinical outcomes are variable, but many dogs experience remission of clinical signs and prolonged survival.

Treatment of children with protein - losing enteropathy after fontan and other complex congenital heart disease procedures in condition with limited human and technical resources.

BackgroundProtein-losing enteropathy (PLE) is a disorder characterized by abnormal and often profound enteric protein loss. It’s relatively uncommon complication of Fontan and other complex congenital heart disease (CCHD) procedures. Because of the complexity and rarity of this disease process, the pathogenesis and pathophysiology of protein-losing enteropathy remain poorly understood, and attempts at treatment seldom yield long-term success.Aim of presentationis to describe single centre experience in diagnosis, evaluation, management and treatment of children with protein-losing enteropathy after Fontan and other CCHD procedures in the current era and in centre with limited human and technical resources, follows with a comprehensive review of protein-losing enteropathy publications, and concludes with suggestions for prevention and treatment.Material and methodologyRetrospectively we analyzed patients with CCHD and protein-losing enteropathy in our institution, starting from January 2000 to December 2012. The including criteria were age between two and 17 years, to have a complex congenital heart disease and available complete documentation of cardiac surgery under cardiopulmonary bypass.ResultsOf all patients we evaluated 18 cases with protein-losing enteropathy, aged 6 to 19 years (mean 14±9); there were three children who had undergone screening procedure for D-transposition, one Tetralogy of Fallot, and remaining 14 patients had undergone Fontan procedures; (anatomic diagnosis are: six with tricuspid atresia, seven with d-transposition, double outlet right ventricle and pulmonary atresia and two with hypoplastic left heart syndrome). The diagnosis of protein-losing enteropathy was made at median age of 5.6 years, ranging from 13 months to 15 years. Diagnosis was made using alpha 1-antitrypsin as a gold marker in stool. By physical examination in 14 patients edema was found, in three ascites, and six patients had pleural effusion. Laboratory findings at the time of diagnosis are: abnormal enteric protein loss was documented at the time of diagnosis in all 18 patients. At the time of diagnosis all patients receiving some form of anticoagulation, 17 patients receiving other medication: 17 – diuretics and ACE inhibitors, 12 digoxin, 9 antiarrhytmics. Cross-sectional echocardiography was performed for all patients and different abnormalities were registered. In 14 patients also magnetic resonance was performed. Therapeutic approach was based on the non-specific medication (diet, diuretics, digoxin, ACE inhibitors, and anticoagulants), heparin and corticosteroids therapy. Long-term response to this type of therapy was registered in three patients. Nine patients underwent treatment with heparin and corticosteroids and no one experienced long term benefit. Despite of needs for catheter therapy or surgical intervention in our study, in the absent of technical and human resources now any one had underwent those procedures. Six patients has been transferred abroad and in five of them surgical intervention was perform.ConclusionProtein-losing enteropathy remains a devastating complication of Fontan procedure and despite in advantages in surgical and medical therapy there is no evidence that protein-losing enteropathy is less common in the current area.