Protein-losing enteropathy as a result of colon polyposis and colon cancer: a multidisciplinary approach to diagnosis and treatment.

A man in his 60s presented to our emergency department with severe peripheral pitting oedema, weight gain, dyspnoea and diarrhoea. Blood tests showed a hypoalbuminaemia of 15 g/L. A suspicion of protein-losing enteropathy arose after the exclusion of albuminuria, cardiac failure, protein deficiency and liver cirrhosis. An abdominal CT scan revealed a wall thickening of the colon, and a subsequent colonoscopy identified multiple large obstructive polyps in the ascending colon. The patient underwent a right hemicolectomy which revealed the presence of tubulovillous polyps and a pT2N0 colon carcinoma. Following surgery, the patient experienced clinical improvement with normalisation of serum albumin and resolution of the oedema.Protein-losing enteropathy should be considered an underlying syndrome in patients with peripheral oedema and hypoalbuminaemia in the absence of cardiac failure, proteinuria, malnutrition and hepatic disease. This diagnostic process requires a multidisciplinary approach. For adequate treatment, the primary cause of protein-losing enteropathy needs to be investigated.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency (RF) ablation were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease. Five procedures were performed in 4 patients (3 men and 1 woman; median age, 49 years; range, 31-71 years). Transhepatic lymphangiography demonstrated abnormal periduodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RF ablation of the leakage sites followed by PTLE using 3:1 ethiodized oil-to-n-butyl cyanoacrylate glue ratio resulted in improved symptoms and serum albumin levels (before procedure, 2.6 g/dL [SD ± 0.2]; after procedure, 3.5 g/dL [SD ± 0.4]; P = .004) over a median follow-up of 16 months (range, 5-20 months). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RF ablation is an option to treat patients with PLE.

Neonatal perspective on central lymphatic disorders.

Lymphatic disorders presenting in the first year of life are difficult to identify and manage given the broad range of underlying etiologies. Neonatal lymphatic disease arising from congenital or acquired conditions results in the abnormal accumulation of lymph fluid in the pleura (chylothorax), peritoneum (chylous ascites) and skin (edema/anasarca). There is also increasing recognition of lymphatic losses through the intestine resulting in protein-losing enteropathy (PLE). While the incidence of lymphatic disorders in neonates is unclear, advances in genetic testing and lymphatic imaging are improving our understanding of the underlying pathophysiology. Despite these advancements, medical management of neonatal lymphatic disorders remains challenging and variable among clinicians.

Comprehensive nutrition guidelines and management strategies for enteropathy in children.

Protein-losing enteropathy (PLE) describes a syndrome of excessive protein loss into the gastrointestinal tract, which may be due to a wide variety of etiologies. For children in whom the protein loss is associated with lymphangiectasia, medical nutrition therapy focused on restricting enteral long-chain triglycerides and thus intestinal chyle production is an integral component of treatment. This approach is based on the principle that reducing intestinal chyle production will concurrently decrease enteric protein losses of lymphatic origin. In patients with ongoing active PLE or those who are on a fat-restricted diet, particularly in infants and young children, supplemental calories may be provided with medium-chain triglycerides (MCT). MCT are absorbed directly into the bloodstream, bypassing intestinal lymphatics and not contributing to intestinal chyle production. Patients with active PLE or who are on dietary fat restriction should be monitored for associated micronutrient deficiencies. In this paper, we seek to formally present recommended nutrition interventions, principles of dietary education and patient counseling, and monitoring parameters in pediatric populations with PLE based on our experience in a busy clinical referral practice focused on this population.

The long-term clinical course of protein-losing enteropathy combined with iron deficiency anemia in Korean toddlers: Possible association with cow's milk protein.

BACKGROUND: Protein-losing enteropathy (PLE), a rare condition with excessive gastrointestinal protein loss, presents with hypoalbuminemia, edema, or ascites. Several cases of PLE combined with severe iron deficiency anemia (IDA) have been reported in infants and toddlers that were considered to result from excessive cow's milk consumption, although the mechanism has not been clearly established. METHODS: We retrospectively reviewed the clinical, laboratory, endoscopic, and radiologic characteristics of patients diagnosed and treated for PLE with IDA between 2015 and 2021. Long-term outcomes were analyzed according to dietary intervention during the follow-up period. RESULTS: A total of 10 patients aged 7.0-26.7 months were enrolled in the study and the median follow-up duration of them was 9.4 months (range, 1.3-18.0). Six of them were fed powdered formula, while two were fed whole cow's milk, and their median daily intake was 700 mL (range, 300-900). The times to normalization of hemoglobin, albumin, and eosinophil count were shorter in patients with dietary elimination of cow's milk protein immediately after diagnosis compared to those with reduced intake or no dietary change. CONCLUSION: Early complete elimination of cow's milk protein should be considered, especially if the laboratory parameters are not normalized with adequate iron supplementation even though the clinical symptoms show improvement. We would like to draw attention to the possibility of the cow's milk protein in the pathogenesis of the condition through the non-IgE-mediated immune reactions.

A very rare cause of protein losing enteropathy: Gaucher disease.

BACKGROUND: Mesenteric lymphadenopathy is a rare manifestation of Gaucher disease (GD) in children and can be accompanied by protein losing enteropathy (PLE). PLE is a difficult-to-treat complication of GD. To date, only a few pediatric GD cases with PLE and massive mesenteric lymphadenopathies have been reported. CASE: Here, we report a girl with chronic neuronopathic GD, whose disease course was complicated by massive mesenteric lymphadenopathies with resultant protein losing enteropathy despite a regular and appropriate enzyme replacement therapy of 60 IU/kg/biweekly until the development of mesenteric lymphadenopathies and 120 IU/kg/biweekly thereafter. CONCLUSIONS: PLE is a devastating and life threatening complication of GD developing despite long term use of high dose ERT. Clinicians should be alert for this complication particularly in GD patients presenting with progressive abdominal distension, edema, ascites and diarrhea or in patients who have already developed mesenteric lymphadenopathies. Timely diagnosis may allow early intervention with previously suggested surgical or medical treatment options. Although there is no specific and effective treatment, surgical and aggressive medical interventions in addition to ERT were reported to relieve diarrhea and halt progression of mesenteric lymphadenopathies.

The effect of assisted enteral feeding on treatment outcome in dogs with inflammatory protein-losing enteropathy.

BACKGROUND: The effect of assisted enteral feeding on treatment outcome in dogs with protein-losing enteropathy (PLE) is unknown. OBJECTIVES: To determine if dogs with inflammatory PLE that had an enteral feeding tube placed had better outcome vs dogs with inflammatory PLE without a feeding tube. ANIMALS: Fifty-seven dogs with inflammatory PLE. METHODS: A retrospective study at a UK referral hospital identified dogs with inflammatory PLE using a standard diagnostic criterion. Positive outcome was defined as survival greater than 6 months or death unrelated to PLE and negative outcome as death related to PLE within 6 months of diagnosis. Several variables were assessed to identify factors for positive outcome using logistic regression. RESULTS: Thirty-five (61%) and 22 (39%) dogs had a positive and negative outcome at 6 months, respectively. Of the 21 dogs that had a feeding tube placed within 5 days of gastrointestinal biopsy, 16 (76%) had a positive outcome and 5 (24%) had a negative outcome. Dogs treated with dietary treatment alone (P = .002) and dogs with an enteral feeding tube (P = .006) were significantly associated with a positive outcome. When stratified by treatment, assisted enteral feeding was significantly associated with a positive outcome in dogs treated with concurrent immunosuppressive treatment (P = .006), but there was insufficient data to evaluate dogs treated with dietary treatment alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Assisted enteral feeding in dogs with inflammatory PLE could be associated with improved treatment outcome, especially in those receiving immunosuppressive treatment, and should be considered in the treatment plan of these dogs.

Successful Treatment of Protein-Losing Enteropathy After Superior Mesenteric Artery Occlusion without Surgery.

BACKGROUND Protein-losing enteropathy as a complication of superior mesenteric artery occlusion is extremely rare and severe, and sometimes requires intestinal resection. However, the ideal treatment strategy has not yet been determined. CASE REPORT A 77-year-old man with underlying hypertension and diabetes was admitted to the Emergency Department with acute abdominal pain after eating. Contrast-enhanced computed tomography revealed complete occlusion of the superior mesenteric artery with thrombosis, and superior mesenteric artery occlusion was diagnosed. It was successfully treated with interventional therapy, followed by continuous intra-arterial prostaglandin E1 infusion and continuous intravenous heparin infusion. However, the patient developed hypoproteinemia and diarrhea about 10 days after the interventional therapy. Colonoscopy and X-ray studies did not reveal any abnormal findings; however, technetium-99m-labeled human serum albumin scintigraphy indicated protein-losing enteropathy. With total parenteral nutrition and protein-rich oral nutrition, with protein intake at twice the amount in a standard diet, serum albumin improved from 15 g/L to 32 g/L after treatment. Additionally, we administered diuretics to avoiding edema related to the hypoproteinemia. The patient recovered from the hypoproteinemia and diarrhea without complications. CONCLUSIONS Protein-losing enteropathy is an extremely rare but critical complication of superior mesenteric artery occlusion. Treating the underlying pathology is the mainstay of protein-losing enteropathy and dietary modifications also play a critical role. Our patient was successfully treated with strict nutritional therapy, combined oral protein-rich nutrition and total parenteral nutrition, which avoided surgery.

Therapeutic Lymphatic Embolization in Pediatric Primary Intestinal Lymphangiectasia.

Primary intestinal lymphangiectasia (IL) can cause leakage of lymphatic fluids into the gastrointestinal tract, eventually leading to protein-losing enteropathy. A 15-year-old male patient, whose disease began at the age of 8 years, recently felt worsening general weakness. After diagnosing abnormal lymphatic lesions in the duodenum through endoscopy with biopsy and contrast-enhanced magnetic resonance lymphangiography, glue embolization of the leaking duodenal lymphatic channel was successfully performed. This procedure is typically reserved for adult patients, although as shown in this case, it can be properly performed in children. His serum albumin level was initially 1.5 g/dL, but elevated to 5.0 g/dL after two sessions of lymphatic embolization. Accordingly, we suggest that embolization could potentially be considered a first-line treatment for focal lesions of primary intestinal IL.

Sjögren syndrome associated with protein-losing enteropathy: case-based review.

The association between Sjögren's syndrome (SS) and protein-losing enteropathy (PLE) was scarcly reported. To analyze the clinical, therapeutic, and outcome characteristics of patients with SS and PLE and also to delineate the potential mechanisms and pathways connecting the gut to SS targeted organ's pathology. Systematic screening was conducted using PubMed/MEDLINE, LILACS, SciELO, Web of Science, and Cochrane, dating 1980 to 2020. SS and PLE were the key words. Eighteen patients with SS and PLE were summarized. The patient's ages ranged between 20 and 88 years, and only 4 were males. Primary SS was observed in most cases. Anti-Ro was detected in 100% of the cases while anti-La was reported in 64% of them. The clinical manifestations were protein loss, edema of the lower limbs, pleural effusion, ascites, facial edema, anasarca, diarrhea, and weight loss. Among these clinical manifestations, edema of the lower limbs was the most severe. Albumin concentration was 0.9-3.4 g/dL which increased to 2.8-4.3 g/dL after treatment. Small bowel biopsy was performed in all of the cases. Concerning the therapy, all the patients received systemic glucocorticoids. All of them improved. The period of onset of improvement ranged from 3 weeks to 36 months (an average of 3 months). The early diagnosis and appropriate therapy of PLE in patients with anti-Ro positive SS and who present edema, anasarca, or hypoalbuminemia is vital for a beneficial outcome. An excellent clinical improvement in all the cases was observed when treated early enough by cortico-therapy, thus preventing patient's deterioration, complications, and reducing morbidity and potential mortality.

Overlap of lymphatic dysplasia in Fontan-associated protein-losing enteropathy and Mucosa-Associated Lymphoid Tissue (MALT lymphoma): implications for management of protein-losing enteropathy.

Lymphatic vessel dysplasia is associated with Fontan-associated protein-losing enteropathy. Extra nodal non-Hodgkin lymphomas including mucosa-associated lymphoid tissue (MALT lymphoma) are associated with lymphatic vessel dysplasia. Here, we describe the case of a 7-year-old with Fontan-associated protein-losing enteropathy who developed MALT lymphoma with a clinical course indicative of interaction between these pathologies and improvement in protein-losing enteropathy after MALT lymphoma treatment. This case suggests a pathophysiologic overlap which has implications for the management of Fontan-associated protein-losing enteropathy.

Decompression of the thoracic duct: A novel transcatheter approach.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

Primary intestinal lymphangiectasia in an adult patient: A case report and review of literature.

BACKGROUND: Primary intestinal lymphangiectasia (PIL), first described in 1961, is a rare disorder of unknown etiology resulting in protein-losing enteropathy. The disease is characterized by dilatation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia, and lymphopenia. Since the severity and location of lymph vessels being affected can vary considerably, the range of associated symptoms is wide from mild lower-limb edema to generalized edema, abdominal and/or pleural effusion, and recurrent diarrhea, among others. Although usually developing in early childhood, we present the case of a 34-year-old woman with PIL. Moreover, we performed a literature review systematically assessing clinical presentation, and provide a practical approach to facilitate diagnosis and therapy of PIL in adults. CASE SUMMARY: Our patient presented with unspecific symptoms of abdominal discomfort, fatigue, nausea, and recurrent edema of the lower limbs. Interestingly, a striking collinearity of clinical symptoms with female hormone status was evident. Additionally, polyglobulia, hypoalbuminemia, hypogammaglobulinemia, and transient lymphocytopenia were evident. Due to suspicion of a bone marrow disease, an extensive diagnostic investigation was carried out excluding secondary causes of polyglobulinemia and hypoalbuminemia. The diagnosis of primary intestinal lymphangiectasia was established after 22 wk by histological analysis of biopsy samples obtained via enteroscopy. Consecutively, the patient was put on a high-protein and low-fat diet with medium-chain triglycerides supplementation leading to significant improvement of clinical symptoms until 2 years of follow-up. CONCLUSION: PIL can be the reason for cryptogenic hypoalbuminemia, hypogammaglobulinemia, and lymphopenia in adulthood. Due to difficulty in correct diagnosis, treatment initiation is often delayed despite being effective and well-tolerated. This leads to a significant disease burden in affected patients. PIL is increasingly been recognized in adults since the majority of case reports were published within the last 10 years, pointing towards an underestimation of the true prevalence. The association with female hormone status warrants further investigation.

Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy.

We herein report a 44-year-old man suffering from systemic edema due to protein-losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and development of collateral veins, which subsequently proved to be a chronic result of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly induced by both intestinal erosion and thrombosis-related lymphangiectasia, which was histologically proven in his surgically-resected ileal stenosis. Elemental diet and anti-TNFα agent improved his hypoalbuminemia after surgery. The rarity of the simultaneous coexistence of SMV obstruction and PLE and the precedence of these complications over typical abdominal symptoms of CD made the clinical course complex.

Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage.

Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.

This report describes two patients with sporadic lymphangioleiomyomatosis complicated by protein-losing enteropathy (PLE). Imaging studies indicated retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one patient; whereas the site in the other patient was intestinal. Treatment with sirolimus led to the complete resolution of PLE within several months; additionally, marked shrinkage was observed in the lymphangioleiomyomas of both cases. These findings suggest that colonic or intestinal lymphatic congestion due to neighboring lymphangioleiomyomas was the mechanism for the development of PLE. At the time of writing this report, the beneficial effect of sirolimus has lasted for more than 3 years.

Restrictive atrial septum after the Fontan procedure.

In this study, three patients presenting with early or late postoperative Fontan complications were identified to suffer from restriction of the native atrial septum. This caused significant obstruction to pulmonary venous return and elevated systemic venous pressure. Dobutamine stress testing was used in one patient to identify this lesion. Transcatheter stenting was performed in the other two patients. Patients improved after relief of the obstruction.

Protein-losing enteropathy in inflammatory bowel diseases.

Protein-loosing enteropathy in patients with inflammatory bowel diseases (IBDs) is an uncommon complication, but should be considered in any patient with hypoproteinemia in whom other causes have been excluded such as concomitant hepatic disease, severe malnutrition or proteinuria. The diagnosis is based on determination of fecal alpha-1 antitripsin clearance and stool analysis. Prognosis depends upon the patient and the disease location, severity and complication. Treatment is directed at control of the underlying IBDs but also includes albumin infusion in the most severe cases of hypoalbuminemia and fluid retention, dietary modifications for recovery and maintenance of nutritional status and supportive care to prevent further complication like deep venous thrombosis. Surgery is not curative in Crohn's disease patients, but in severe protein-loosing enteropathy with severe disease, not responding to conventional therapy, it may be the best choice.