Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.

BACKGROUND: There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity. METHODS: This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances. RESULTS: Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE. CONCLUSIONS: Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.

An undernutrition screening score for dogs with protein-losing enteropathy: A prospective multicenter study.

BACKGROUND: The impact of undernutrition in dogs with protein-losing enteropathy (PLE) caused by inflammatory enteritis, intestinal lymphangiectasia, or both and which variables are most predictive of outcome are unknown. OBJECTIVES: Develop an undernutrition screening score (USS) for use at the time of diagnosis of PLE in dogs, which is predictive of outcome. ANIMALS: Fifty-seven dogs with PLE prospectively recruited from 3 referral hospitals in the United Kingdom. METHODS: An USS based on the presence and severity of 5 variables: appetite, weight loss, and body, muscle, and coat condition and scored out of 15, with higher scores reflecting worse undernutrition, was calculated at the time of diagnosis. Follow-up information was obtained for at least 6 months. RESULTS: Dogs that failed to achieve clinical remission within 6 months had higher USS at diagnosis compared with dogs that achieved remission (median, 7.5; range, 2-14 and median, 5; range, 0-14, respectively). The USS at diagnosis gave an area under the receiver operating characteristic curve (AUC) of 0.656 for predicting nonclinical remission within 6 months, whereas a score consisting of just epaxial muscle loss and coat condition resulted in a larger AUC of 0.728. CONCLUSIONS AND CLINICAL IMPORTANCE: Of the 5 variables assessed in the USS, a combination of epaxial muscle loss and coat condition was most predictive of not achieving clinical remission within 6 months in dogs with PLE. Additional studies will help determine the effect of changes in USS and the 5 associated variables after diagnosis on outcome variables in these dogs.

Clinical Manifestation of Cytomegalovirus-Associated Protein-Losing Enteropathy in Children.

In children, CMV-associated protein-losing enteropathy (PLE) is characterised by a benign course and spontaneous healing but can lead to generalised oedema. Poorly defined, it is diagnosed after unnecessary invasive tests. Children with CMV-associated PLE between 2009 and 2019 in two French hospitals are retrospectively described. Clinical and biological signs, CMV identification, endoscopy and histological findings, disease management and course are analysed. CMV-associated PLE is proven in 21 immunocompetent and 22 immunosuppressed patients, with ages consistent with primo-infection and reactivation, respectively. The digestive symptoms prevail in immunocompetent children, mainly with vomiting (85.7% versus 50%, CI [1.2; 39.2], p = 0.02). Immunocompetent patients show more oedema (61.9% versus 4.5%, CI [3.6; 1502.4], p < 0.001), linked to more severe hypoalbuminemia (21.2 g/L [17.6-25.7] versus 29.6 g/L [24.9-33.9], p = 0.01). A severe course is observed in 23.8% of the immunocompetent patients and 54.5% of the immunosuppressed ones (p = 0.06). Evidence of CMV infection based on non-invasive methods is found on 88.9% of immunocompetent and 95.5% of immunosuppressed patients (p = 0.58), while endoscopy was performed on 95.2% and 100% of them, respectively (p = 0.48), without any therapeutic change. Thus, CMV-associated PLE should be suspected in children with generalised oedema. Not as benign as previously described, it can be confirmed using non-invasive tests.

Child with protein losing enteropathy as presentation of collagenous duodenitis and eosinophilic gastroenteritis.

Background: Collagenous duodenitis and gastritis are rare histopathological findings in children. Patients and methods: : We describe a four-year old girl, who presented with non-bloody diarrhea for two months and progressive edema with an albumin of 16g/dl. Results: The diagnosis of a protein losing enteropathy was made. Extensive investigations withheld only an infectious cause of the protein losing enteropathy (cytomegalovirus and adenovirus). However, the patients still required repetitive albumin infusions 3.5 months after onset of symptoms without spontaneous recovery. Therefore, a new endoscopic work-up was performed. Duodenal biopsies revealed collagen deposition, in association with a high number of eosinophils and mast cells throughout different parts of the gastrointestinal tract. Conclusions: The collagen deposition seems to be triggered by an eosinophilic gastrointestinal disorder. Treatment was started with amino acid-based formula, oral iron therapy, an antihistamine, and a proton pomp inhibitor that resulted in persistent normalization of serum albumin already after 1.5 weeks.

Does intestinal obstruction influence hypo-albuminemia: assessment of the physio-pathogenesis of protein-losing enteropathy with literature review.

BACKGROUND: Non-steroidal anti-inflammatory drug (NSAID) use may cause diaphragm-like lesions in the bowel. Although NSAID-enteropathy is among the causes of protein-losing enteropathy (PLE), intractable hypoalbuminemia is rare. CASE REPORT: Here, we discuss a case of NSAID-enteropathy with a diaphragm-like disease that presented with Protein Losing Enteropathy (PLE) rather than obstruction. The hypoalbuminemia recovered immediately after resection of the obstructive segment, despite ongoing annular ulcerations in the early postoperative period. Thus, it was not clear whether obstructive mechanisms influenced resistant hypoalbuminemia besides the ulcers. We also reviewed the English-written literature for "diaphragm-type lesion, NSAID-enteropathy, obstruction, and protein-losing enteropathy". We noted that the role of obstruction in the pathophysiology of PLE was not clear. CONCLUSIONS: As our case and a couple of cases reported in literature, slow-onset obstructive pathology seems to contribute to well-known factors: inflammatory response, exudation, tight-junction dysfunction, and increase in permeability in the physiopathology of NSAID-induced PLE. Factors such as distention-induced low-flow ischemia and reperfusion, cholecystectomy-related continuous bile flow, bacterial overgrowth-related bile deconjugation and concomitant inflammation are among other potential influencers. The possible role of a slow-onset obstructive pathology in the physiopathology of NSAID-induced and other PLE needs to be further elucidated.

Computed tomographic features of focal lipogranulomatous lymphangitis for differentiating from malignant intestinal lesions in a dog.

An eight-year-old Maltese dog presented with diarrhea and anorexia. Ultrasonography revealed marked focal wall thickening with loss of layering in the distal ileum. Contrast-enhanced computed tomography (CT) revealed a preserved wall layer with hypoattenuating middle wall thickening. In some segments of the lesion, small nodules protruding toward the mesentery from the outer layer were observed. Histopathology revealed focal lipogranulomatous lymphangitis (FLL) with lymphangiectasia. This is the first report to describe the CT features of FLL in a dog. CT features of preserved wall layers with hypoattenuating middle wall thickening and small nodules can assist in diagnosing FLL in dogs.

Intestinal helminths-an outlander in a case of protein losing enteropathy.

Malabsorption is the major disease burden in tropical countries. Both primary and secondary forms exist and a secondary form overshadows the primary category. Intestinal parasitic infections lead to secondary form of tropical malabsorption in both native and travelers and presentation varies from mild glossitis to severe protein losing enteropathy. The underlying condition is often masked unless an endoscopic biopsy is performed. This is followed by a histopathological examination which unravels the etiology.

Periorbital edema as the presenting sign of protein-losing enteropathy from excessive cow's milk intake.

We report the case of a 15-month-old girl who presented with bilateral, positional periorbital edema, systemic hypoalbuminemia, and profound iron deficiency caused by excessive cow's milk intake. Her symptoms rapidly improved with reduction of cow's milk intake and iron supplementation.

A case of familial adenomatous polyposis with protein-losing enteropathy treated by laparoscopic total colorectal resection: A literature review.

Familial adenomatous polyposis (FAP) with protein-losing enteropathy is a rare disorder and is difficult to treat medically. A 74-year-old female patient was referred to our hospital with a chief complaint of anorexia. Lower gastrointestinal endoscopy showed multiple adenomas from the ascending colon to the rectum and adenocarcinoma in the sigmoid colon and descending colon. Laboratory findings showed hypoalbuminemia (albumin 1.6 mg/dl). Protein leak scintigraphy using 99mTc-HSAD found a protein leak from the colon. Although hypercaloric infusion was administered, the nutritional status was not improved and albumin transfusion was required. The patient underwent laparoscopic total proctocolectomy, ileal pouch-anal anastomosis, and temporary ileostomy. She had a good postoperative course and the hypoalbuminemia normalized in a few weeks. The patient underwent temporary ileostomy reversal. Here we report a case of FAP with protein-losing enteropathy who underwent laparoscopic total proctocolectomy, which resulted in improvement of the protein leak as well as cancer treatment.

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.

Incidence of relapse of inflammatory protein-losing enteropathy in dogs and associated risk factors.

BACKGROUND: Dogs with inflammatory protein-losing enteropathy (iPLE) that attain remission may be at risk of subsequent relapse. OBJECTIVES: To determine the incidence of relapse of iPLE in dogs that have previously attained complete clinical and biochemical remission and identify associated risk factors. ANIMALS: Seventy-five client-owned dogs diagnosed with iPLE. METHODS: Medical records of dogs diagnosed with iPLE based on histopathology of intestinal biopsy specimens between March 2010 and March 2020 were retrospectively reviewed. Variables were recorded from the time of investigation at histopathologic diagnosis and subsequent follow-up information was obtained from the records of referring veterinarians. RESULTS: Twenty-three dogs (31%) achieved sustained remission without documentation of relapse for at least 2 years. Nineteen dogs (25%) achieved remission, but then subsequently relapsed within 2 years of histopathologic diagnosis, and 33 dogs (44%) never achieved remission with disease-associated death occurring a median of 19 (range, 3-114) days after histopathologic diagnosis. Dogs that achieved remission and subsequently relapsed had significantly higher poor dietary compliance, as defined by frequent scavenging or changing from the recommended diet compared to dogs with sustained remission (P = .01). CONCLUSIONS: Inflammatory PLE is associated with a high rate of relapse in dogs. Ensuring owners adhere to dietary recommendations might help prevent subsequent relapse in dogs with iPLE that attain initial remission.

[Hybrid treatment of protein-losing enteropathy in a patient with univentricular circulation].

Protein-losing enteropathy (PLE) is a severe Fontan complication. This is a case report of the first hybrid treatment of PLE in Denmark of an 11-year-old Fontan patient with severe symptoms (diarrhoea, fatigue and swelling) and low albumin level. Diagnostics included intranodal and intrahepatic dynamic contrast magnetic resonance lymphangiography. The hybrid intervention consisted of selective lymphatic duct embolisation and innominate vein turn-down to treat PLE. The interventions went well, and two months after discharge the patient was relieved from PLE symptoms, the albumin level was normalised, and the patient felt more energetic.