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Aim: To investigate the correlation between capsule endoscopy (CE) classification of primary intestinal lymphangiectasia (PIL) and computed tomography (CT) lymphangiography (CTL)., Materials and Methods: A total of 52 patients with diagnosed PIL were enrolled. All patients were examined using CTL and small intestinal CE before surgery. CE assessments included the morphology, scope, colour, and size of lesions. CTL assessments included intestinal wall, lymphatic vessel dilatation, lymph fluid reflux, and lymphatic fistula. Patients were divided into three groups according to type diagnosed by CE, and the CTL characteristics were analysed among the groups., Results: CE showed 15 patients with type I, 27 with II, and 10 with type III. Intestinal wall thickening was observed in 15 type I, 21 type II, and seven type III. Pericardial effusion was observed in only three type I patients; the difference among types was statistically significant (p=0.02). Abnormal contrast agent distribution in the intestinal wall and mesentery was observed in 15 type II patients, and the difference was significantly greater than that of types I and III (p=0.02). Abnormal contrast agent distribution in the abdominal cavity was observed in 12 type II, and the difference was statistically significant (p=0.03)., Conclusion: The CE PIL classification reflects the extent and scope of intestinal mucosa lesions; CTL more systematically demonstrates abnormal lymphatic vessels or reflux, and its manifestations of PIL are related to the CE classification. The combination of CTL with CE is useful for accurately evaluating PIL, and provides guidance for preoperative assessment and treatment management of PIL patients., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL)., Aim: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes., Methods: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type., Results: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers., Conclusion: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Defects in the PIEZO1 gene cause lymphatic dysplasia in an autosomal recessive manner, mostly by loss-of-function variants. Moreover, since 2019, the role of PIEZO1 in bone formation has been established, but there have been no PIEZO1-related cases presenting definite skeletal involvement to date. A 21-year-old male with primary lymphatic dysplasia had some other distinctive clinical features, including multiple fracture history during infancy, thoracolumbar scoliosis, short stature, and left-sided facial bone hypoplasia. We analyzed the whole exome of the patient and found two novel pathogenic variants of PIEZO1 in trans: a 93.7 kb heterozygous deletion (chr16:88,782,477-88,876,207; exon 1-50) and c.2858G>A (p.Arg953His). Sanger sequencing validated the deletion with breakpoints, and each variant was inherited from a different parent. This study presented an extremely rare case of a patient with lymphatic dysplasia caused by compound heterozygous variants of PIEZO1, along with additional clinical manifestations including several skeletal phenotypes., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Primary intestinal lymphangiectasia is an unusual cause of protein losing enteropathy due to either congenital malformation or obstruction of lymphatics of intestine. The disease can affect all or only a small part of the small intestine. Peripheral lymphedema may be associated. The diagnosis is based on endoscopic and histopathological findings. A 30-year-old woman presents lower extremity edema with hypoproteinemia, hypoalbuminemia, and hypogammaglobulinemia. Tc-labeled human serum albumin nanocolloid lymphoscintigraphy of the lower extremity demonstrated a dermal backflow in the right extremity consistent with lymphedema and an unusual ileal uptake on SPECT/CT. Diagnosis is confirmed on histopathological evaluation of biopsy of ileum.

Generalized lymphatic dysplasia (GLD), characterized by lymphedema, lymphangiectasias, chylothorax, effusions, represents a recognized cause of fetal hydrops. We describe for the first time recurrent pregnancies showing different ultrasound presentations of lymphatic dysplasia. The first fetus displayed diffuse subcutaneous cysts and septations while the second one presented fetal hydrops. Exome sequencing results at 18 gestational weeks in the second pregnancy showed compound heterozygosity for two novel PIEZO1 variants, afterwards detected also in the first fetus and in the heterozygous parents. Both ultrasound and genetic findings expand the current knowledge of PIEZO1-related GLD. We suggest exome sequencing in hydropic fetuses with normal cytogenetics and in pregnancies with recurrent hydrops/lymphatic dysplasia., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Competing interests: None declared.

Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by congenital lymphedema, intestinal lymphangiectasia, facial dysmorphism, and variable intellectual disability. Known disease genes include CCBE1, FAT4, and ADAMTS3. In a patient with clinically diagnosed Hennekam syndrome but without mutations or copy-number changes in the three known disease genes, we identified a homozygous single-exon deletion affecting FBXL7. Specifically, exon 3, which encodes the F-box domain and several leucine-rich repeats of FBXL7, is eliminated. Our analyses of databases representing >100,000 control individuals failed to identify biallelic loss-of-function variants in FBXL7. Published studies in Drosophila indicate Fbxl7 interacts with Fat, of which human FAT4 is an ortholog, and mutation of either gene yields similar morphological consequences. These data suggest that FBXL7 may be the fourth gene for Hennekam syndrome, acting via a shared pathway with FAT4., (© 2019 Wiley Periodicals, Inc.)

Objectives: Loss of the complement inhibitor CD55 leads to a syndrome of early-onset protein-losing enteropathy (PLE), associated with intestinal lymphangiectasia and susceptibility to large-vein thrombosis. The in vitro and short-term treatment benefits of eculizumab (C5-inhibitor) therapy for CD55-deficiency have been previously demonstrated. Here we present the 18-months treatment outcomes for 3 CD55-deficiency patients with sustained therapeutic response., Methods: Three CD55-deficiency patients received off-label eculizumab treatment. Clinical and laboratory treatment outcomes included frequency and consistency of bowl movements, weight, patient/parent reports of overall well-being, and serum albumin and total protein levels. Membrane attack complex deposition on leukocytes was tested by flow cytometry, before and during eculizumab treatment., Results: Marked clinical improvement was noted in all 3 patients with resolution of PLE manifestations, that is, diarrhea, edema, malabsorption, overall well-being, growth, and quality of life. In correlation with the clinical observations, we observed progress in all laboratory outcome parameters, including increase in albumin and total protein levels, and up to 80% reduction in membrane attack complex deposition on leukocytes (P < 0.001). The progress persisted over 18 months of treatment without any severe adverse events., Conclusions: CD55-deficiency patients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine.

Objective: Intestinal lymphangiectasia (IL; primary or secondary) is an important cause of protein-losing enteropathy. We evaluated the clinicolaboratory profile, response to therapy, complications, and outcome of children with primary IL (PIL)., Methods: Consecutive children (≤18 years) diagnosed with PIL (clinical setting, typical small bowel histopathology, and exclusion of secondary causes) from 2007 to 2017 were evaluated., Results: Twenty-eight children with PIL (16 boys, age at symptom onset-12 [1-192] months and at diagnosis 8 [1-18] years) were studied. Pedal edema (93%), chronic diarrhea (78.6%), and recurrent anasarca (64%) were the common presentations. Ascites, pleural, and pericardial effusion were seen in 64 (n-18; chylous-5, non-chylous-13), 18, and 18% cases, respectively. Hypoproteinemia, hypoalbuminemia, hypocalcemia, and lymphopenia were present in 82, 82, 75 and 39% cases, respectively. Duodenal biopsy established the diagnosis in 86% cases, while 14% required distal small bowel biopsies. Dietary therapy was given in all and 6 cases required additional therapy (octreotide-6, tranexamic acid-3, and total parenteral nutrition-1). Lymphedema (3/5 vs. 1/23), pleural effusion (4/5 vs. 1/23), and the need for additional therapy (4/5 vs. 2/23) were significantly more in patients with chylous ascites (n = 5) than those without chylous ascites (n = 23). Twenty-four cases in follow-up (39 [6-120] months) showed improvement; however, 8 required readmission (symptom recurrence-6 [25%], complication-2 [8.3%], Budd Chiari Syndrome-1, and abdominal B cell lymphoma-1)., Conclusion: Presence of chylous ascites suggests severe disease in children with PIL. Majority of PIL children respond to dietary therapy; only 20% need additional therapy. Long-term follow-up is essential to monitor for symptoms relapse and complications., (© 2019 S. Karger AG, Basel.)

We report the first case of nonimmune hydrops fetalis (NIHF) associated with a recessive, in-frame deletion of V205 in the G protein-coupled receptor, Calcitonin Receptor-Like Receptor (h CALCRL ). Homozygosity results in fetal demise from hydrops fetalis, while heterozygosity in females is associated with spontaneous miscarriage and subfertility. Using molecular dynamic modeling and in vitro biochemical assays, we show that the hCLR(V205del) mutant results in misfolding of the first extracellular loop, reducing association with its requisite receptor chaperone, receptor activity modifying protein (RAMP), translocation to the plasma membrane and signaling. Using three independent genetic mouse models we establish that the adrenomedullin-CLR-RAMP2 axis is both necessary and sufficient for driving lymphatic vascular proliferation. Genetic ablation of either lymphatic endothelial Calcrl or nonendothelial Ramp2 leads to severe NIHF with embryonic demise and placental pathologies, similar to that observed in humans. Our results highlight a novel candidate gene for human congenital NIHF and provide structure-function insights of this signaling axis for human physiology., (© 2018 Mackie et al.)

Primary intestinal lymphangiectasia (PIL), Waldmann's disease, is a rare disorder of unknown etiology characterized by dilated intestinal lacteals leading to lymph leakage into the small-bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. The main symptom is bilateral lower limb edema. Edema may be moderate to severe including pleural effusion, pericarditis or ascites. Protein-losing enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance and diagnosis by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of biopsies. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Several B-cell lymphomas of the gastrointestinal tract or with extra-intestinal localizations were reported in PIL patients. A long-term strictly low-fat diet associated with medium-chain triglyceride and liposoluble vitamin supplementation is the cornerstone of PIL medical management. Octreotide, a somatostatin analog, have been proposed with an inconsistent efficacy in association with diet. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. A prolonged clinical and biological follow-up is recommended., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103 + DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.

Rationale: Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation., Diagnoses: A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia., Interventions/outcomes: Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein diet, supplements of fat-soluble vitamins, and avoiding long-chain fatty acids, with marked clinical improvement., Lessons: This work shows that: 1)-standard EGD and colonoscopy may miss characteristic lesions of PIL, 2)-enteroscopy or terminal ileal intubation at colonoscopy may be required for the diagnosis because lesions are typically located in distal duodenum/jejunoileum; and 3)-PIL can first present in the very elderly even with symptoms of short duration., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Intestinal lymphangiectasia (IL) is a rare enteropathy involving the expansion and rupture of intestinal lymphatic channels. Although several reports have studied cases of primary IL (PIL), this condition is very rare, and is even less commonly encountered in infants. This study aimed to investigate the nutritional therapy and effect assessment of chylous reflux disorder caused by PIL in infants., Patient Concerns: Infantile patients were enrolled in the Affiliated Beijing Shijitan Hospital of the Capital Medical University between January 2012 and March 2014. The minimum age of onset was 4 months and the maximum age of onset was 16 months, with an average age of 4.9 months., Diagnoses: All children were inpatient who had been diagnosed with chylous reflux syndrome (chylothorax and/or chylic abdomen) caused by PIL., Interventions: Retrospective analysis and individualized nutrition therapy of these cases were carried out. Finally, nutritional therapy and prognosis of PIL were assessed and summarized., Outcomes: All the children survived, showed improvement in the serum total protein, albumin, and HGB levels after nutritional therapy. After comprehensive nutritional therapy, we were able to achieve diarrhea control for all the 9 patients, and after treatment, the children passed soft, yellow stools 1 to 2 times/d. After treatment, the height and weight of all patients increased to within the normal ranges of the World Health Organization standard chart. The mean serum albumin level reached 41.3 g/L. All nutrition-related indicators were found to have significant improvement compared with the baseline levels., Lessons: The results revealed that nutritional therapy for the 9 children with PIL was effective, and it may be able to improve the clinical syndromes and symptoms of children with PIL and promote recovery., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To analyse the findings of multiple detector computed tomography (MDCT) after direct lymphangiography in primary intestinal lymphangiectasia (PIL)., Methods: Fifty-five patients with PIL were retrospectively reviewed. All patients underwent MDCT after direct lymphangiography. The pathologies of 16 patients were confirmed by surgery and the remaining 39 patients were confirmed by gastroendoscopy and/or capsule endoscopy., Results: After direct lymphangiography, MDCT found intra- and extraintestinal as well as lymphatic vessel abnormalities. Among the intra- and extraintestinal disorders, 49 patients had varying degrees of intestinal dilatation, 46 had small bowel wall thickening, 9 had pleural and pericardial effusions, 21 had ascites, 41 had mesenteric oedema, 20 had mesenteric nodules and 9 had abdominal lymphatic cysts. Features of lymphatic vessel abnormalities included intestinal trunk reflux (43.6%, n = 24), lumbar trunk reflux (89.1%, n = 49), pleural and pulmonary lymph reflux (14.5%, n = 8), pericardial and mediastinal lymph reflux (16.4%, n = 9), mediastinal and pulmonary lymph reflux (18.2%, n = 10), and thoracic duct outlet obstruction (90.9%, n = 50)., Conclusions: Multiple detector computed tomography after direct lymphangiography provides a safe and accurate examination method and is an excellent tool for the diagnosis of PIL., (© 2017 The Royal Australian and New Zealand College of Radiologists.)

Objective: The purpose of this study was to investigate the role of Fat4 and Dachsous1 signaling in the lymphatic vasculature., Approach and Results: Phenotypic analysis of the lymphatic vasculature was performed in mice lacking functional Fat4 or Dachsous1 . The overall architecture of lymphatic vasculature is unaltered, yet both genes are specifically required for lymphatic valve morphogenesis. Valve endothelial cells (Prox1 high [prospero homeobox protein 1] cells) are disoriented and failed to form proper valve leaflets. Using Lifeact-GFP (green fluorescent protein) mice, we revealed that valve endothelial cells display prominent actin polymerization. Finally, we showed the polarized recruitment of Dachsous1 to membrane protrusions and cellular junctions of valve endothelial cells in vivo and in vitro., Conclusions: Our data demonstrate that Fat4 and Dachsous1 are critical regulators of valve morphogenesis. This study highlights that valve defects may contribute to lymphedema in Hennekam syndrome caused by Fat4 mutations., (© 2017 American Heart Association, Inc.)

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.

Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine., (© The Author(s) 2015.)

Objectives: Lymphangiomatous lesions involving the gastrointestinal (GI) tract remain incompletely characterized, and their clinical and histopathologic features have not been systematically evaluated. The distinction between a primary lymphatic malformation (lymphangioma) and a dilation of existing lymphatics (lymphangiectasia) is of clinical significance, since lymphangiectasia may occur in the setting of lymphatic obstruction due to an unsampled malignancy. We describe clinical and morphologic features of lymphangiomas of the GI tract in adult and pediatric populations and contrast them with lymphangiectasia., Methods: We performed a retrospective review of adult and pediatric lymphangiomas and lymphangiectasia involving the GI tract., Results: Thirty-six cases of lymphangioma and lymphangiectasia were retrieved, and clinical presentation and histologic features were compared. Lymphangiomas had distinct clinical presentations in adults and children, with adult lesions being more frequently asymptomatic and more frequently involving the superficial mucosal layers of the GI tract. Microscopically, lymphangiomas mostly consisted of confluent dilated spaces with a smooth muscle component. This appearance differed from lymphangiectasia, which lacked a complete distinct endothelial or smooth muscle lining and diffusely involved the mucosa and submucosa., Conclusions: Morphologic features of GI tract lymphangiomas can be reliably distinguished from lymphangiectasia by clinical and pathologic characteristics., (Copyright© by the American Society for Clinical Pathology.)

After an earlier study defining immunolabeled lymphoid follicles, obstructed lymphatics, and granulomas of the diseased ilea of 24 Crohn's disease patients, we chose to trace the lymphatics of these cases and 10 additional by serial sectioning. Particular attention was given to establishing physical continuity between granuloma-obstructed lymphatics and lymphatics with 'lymphocytic thrombi'. Formalin-fixed paraffin-embedded tissue blocks from resected diseased ilea and proximal colons from 34 patients were reviewed. Patients were 13 men and 21 women, aged 14-60 years. Duration of disease ranged from 1 month to 10 years. Immunohistochemistry employed D2-40 antibody to label lymphatics and anti-CD68 to label granulomas. Twenty-nine of the 34 (85%) resection tissues had lymphangectasia, in mucosa, submucosa, and subserosa. In 53% of the specimens, lymphatics of the various layers were obstructed by granulomas that filled the lumina. In 44%, 15/34, there were also distended lymphatics that were totally plugged with lymphocytes. In 10 of the 15, serial sections revealed continuity between the lymphocyte-plugged lymphatics and the endolymphatic granulomatous obstruction downstream. In 5 of the cases, D2-40 immunostaining revealed redundant lymphatic endothelium interwoven with the granuloma cells. Granulomas totally obstruct lymphatics in all layers of the intestine in Crohn's disease. Upstream of these obstructions, lymphatics are distended with lymphocytes. The degree and extent of this potentially irreversible 'lymphangitis nodosa' have undoubtedly confounded treatment regimens and clinical trials. There currently are no imaging methods to demonstrate the lymphangitis, nor treatments to resolve it., (© 2014 APMIS. Published by John Wiley & Sons Ltd.)

Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, and vitamin D malabsorption resulting in osteoporosis. We report here a case of long-lasting misdiagnosed PIL with a peculiar liver picture, characterized by a very high stiffness value at transient elastography, which decreased with clinical improvement. The complex interplay between lymphatic and hepatic circulatory system is discussed., (© 2014 by the American Association for the Study of Liver Diseases.)

Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death.

Background/aims: We classified intestinal lymphangiectasia (IL) into two categories, the white and non-white villi types, and evaluated their clinical characteristics and therapeutic responses., Methods: Of the 988 patients who underwent double-balloon enteroscopy, 14 consecutive patients (7 men and 7 women, median age at onset 34 years) were enrolled with immunohistochemically confirmed IL with protein-losing enteropathy., Results: Enteroscopically the white villi type (n = 8) showed white plaques and white-tipped villi were scattered in the small bowel, while non-white villi type (n = 6) showed that apparently normal but under more detailed observation, low and round villi with a normal color were diffused. The serum albumin levels and fecal α1-antitrypsin clearance before treatment were significantly worse in the non-white villi type (p = 0.017 and 0.039, respectively), whereas the serum immunoglobulin A and M levels were significantly lower in the white villi type (p = 0.010 and 0.046, respectively). At gastroscopy, a non-cirrhotic snakeskin appearance was significantly observed in the non-white villi type (p = 0.015). The corticosteroid response was better in the non-white villi type (p = 0.015)., Conclusion: Two distinct subgroups were found in IL. This classification was useful in pathophysiological clustering and in predicting the therapeutic response., (© 2014 S. Karger AG, Basel.)

Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal., (© 2013 Veterinary Radiology & Ultrasound.)

Primary intestinal lymphangiectasia (PIL) is a protein-losing, exsudative gastroenteropathy causing lymphatic obstruction. Diagnosis depends on clinical examination and histological findings. Conservative treatment modalities include a low-fat diet and enteral nutritional therapy in order to reduce enteric protein loss and to improve fat metabolism. Other treatment options consist of administration of antiplasmin or octreotide to lower lymph flow and secretion. We report on a 58-year-old patient who underwent exploratory laparotomy due to a worsening physical status, recurrent chylaskos and leg oedema under conservative dietary therapy. Intraoperative findings showed a typical PIL of the jejunum about 20 cm distal to the Treitz's ligament. Histological examinations confirmed this diagnosis. One year after segmental small bowel resection (105 cm) with end-to-end anastomosis the patient is healthy, free of symptoms, has gained weight and his serum protein level has increased. Intraabdominal ascites and leg oedema have not reoccurred since.

Background: The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported., Hypothesis/objectives: To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity., Animals: 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies., Methods: Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated., Results: Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%., Conclusions and Clinical Importance: Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

To investigate the toxicity and carcinogenic potential of indole-3-carbinol (I3C), the National Toxicology Program has conducted 13-week subchronic studies in Fisher 344 rats and B6C3F1 mice, and chronic 2-year bioassays in Sprague-Dawley rats and B6C3F1 mice. While the chronic study results are not yet available, subchronic study results and short-term special evaluations of interim sacrifices in the 2-year rat bioassay are presented. F344 rats were orally gavaged ≤300 mg I3C/kg body weight 5 days a week for 13 weeks. Rats treated with ≥150 mg/kg demonstrated a dose-related dilation of lymphatics (lymphangiectasis) of the duodenum, jejunum, and mesenteric lymph nodes. Material within dilated lacteals stained positively for Oil Red O and Sudan Black, consistent with lipid. Electron microscopic evaluation confirmed extracellular lipid accumulation within the villar lamina propria, lacteals, and within villar macrophages. Analyses of hepatic and pulmonary CYP1A enzymes demonstrated dose-dependent I3C induction of CYP1A1 and 1A2. B6C3F1 mice orally gavaged ≤250 mg I3C/kg body weight did not demonstrate histopathological changes; however, hepatic CYP induction was similar to that in rats. The histopathologic changes of intestinal lymphangiectasis and lipidosis in this study share similarities with intestinal lymphangiectasia as observed in humans and dogs. However, the resultant clinical spectrum of protein-losing enteropathy was not present.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease. Typically, ISH patients present with progressive painful joint contractures, intractable diarrhea, hyperpigmented skin lesions, and peri-anal fleshy nodules. We report a case of a 19-month-old male child with atypical ISH presentation. His main clinical finding was protein-losing enteropathy due to intestinal lymphangectasia. This report is intended to enhance awareness about the gastrointestinal tract presentation of ISH.

Distended lacteals, described as expanded white villi in duodenum, are strongly indicative of primary intestinal lymphangiectasia. In the present study, we evaluated the significance of white spots present in the duodenal mucosa of dogs with lymphocytic plasmacytic enteritis (LPE). Fifty dogs with LPE were included in this study, and white spots were detected in the duodenal mucosa in 22 dogs during endoscopy. Hypoproteinemia was more frequent in dogs with white spots than in dogs without spots (p = 0.02). Serum protein and albumin concentration were significantly lower in LPE dogs with white spots (p = 0.038) compared to LPE dogs without white spots (p = 0.039). There was a significant correlation between white spots density and lymphatic dilatation histological scores (p = 0.023; ρ = 0.481). These results suggest that the presence of white spots in the duodenal mucosa of dogs is not a finding exclusive for intestinal lymphangiectasia. Low serum protein and albumin concentrations together with lymphatic dilatation seem to be related to the presence of white spots in the duodenal mucosa of LPE dogs.

Background: Primary intestinal lymphangiectasia (PIL) is a rare digestive disease and most articles on this condition are isolated case reports., Aims: Our purpose is to investigate the clinical characteristics, therapeutic management, and outcome of PIL through case studies., Methods: We conducted a retrospective analysis and obtained detailed clinical information for four PIL patients treated at our institution. A MEDLINE database search was also performed using the search term "intestinal lymphangiectasia" and all pertinent literature was carefully reviewed., Results: Four children treated in our department showed elevated IgE and a good response to diet intervention. After reviewing the literature, we conducted statistical analysis on the basis of all the cases, with a total of 84 cases. Thirty-eight cases have been reported with diet treatment, 24 (63%) of whom showed apparent improvement in clinical symptoms and laboratory parameters. Four cases (5%) had a malignant transformation of lymphoma, and the average time from PIL onset to lymphoma diagnosis was 31 years (range, 19-45 years). No difference was observed regarding the presence of major clinical manifestations among children and adults. Diet intervention in children was more effective than that in adults., Conclusions: Diet intervention is the cornerstone of PIL medical management, which was found to be more effective in children than in adults. Early diagnosis and treatment of IL is of great importance for effective diet therapy. An elevated IgE level should be monitored periodically since it could be an indication of malignant transformation-lymphoma.

Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. The symptoms usually start in early infancy. We report a case of secondary hyperparathyroidism, osteopenia, monoclonal gammopathy and digital clubbing in a 57-year-old patient with a 12-year history of discontinuous diarrhea. Malabsorption with inability to gain weight, and finally weight loss and formation of leg edema were associated with protein-losing enteropathy. A low-fat diet associated with medium-chain triglyceride supplementation was clinically effective as medical management in reducing diarrhea and leg edema, and promoting weight gain. Double-balloon enteroscopy and small bowel biopsy histopathology confirmed dilated intestinal lacteals. Digital clubbing associated with primary intestinal lymphangiectasia which may causally be related to chronic platelet excess has not been reported before.