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.

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.

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.

• Primary intestinal lymphangiectasia
• Waldmann´s disease
• Protein losing enteropathy
• Hypoproteinemia
• Case report

• Adult
• Child, Preschool
• Diet, Fat-Restricted
• Edema/etiology
• Female
• Humans
• Lymphangiectasis, Intestinal/complications
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/therapy
• Protein-Losing Enteropathies/diagnosis
• Protein-Losing Enteropathies/etiology
• Protein-Losing Enteropathies/therapy
• Triglycerides

• Adolescent
• Adult
• Balloon Enteroscopy/methods
• Child
• Feasibility Studies
• Female
• Humans
• Intraoperative Care/methods
• Laparotomy/methods
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/surgery
• Lymphography/methods
• Male
• Preoperative Care/methods
• Tomography, X-Ray Computed/methods

• direct lymphangiography
• multiple detector computed tomography
• primary intestinal lymphangiectasia

Primary intestinal lymphangiectasia (PIL) is a rare disorder, especially in adults. It causes a local disruption of chylus transport and is part of the exudative gastroenteropathies. Conservative therapy includes dietary measures or somatostatin medication. Taking the differential diagnosis of PIL into consideration is a major challenge, since patients suffering from PIL may present with diarrhoea and lymphedema or chylous ascites. This can be explained by the chronic lymphedema of the bowel leading to dilation of the vessels (intraluminal loss) and sometimes even to a rupture (peritoneal loss). Push–pull enteroscopy and capsule endoscopy are the proper interventional diagnostic tools to discover PIL. Exploratory laparoscopy may be useful in unclear cases. Surgical resection of the altered intestine has been described with positive results. Exploratory laparoscopy may even be a diagnostic tool in unclear cases. Resection of the altered intestine is a treatment option in symptomatic and treatment-refractory cases.

• Gamma globulin
• Linfangiectasia intestinal primaria
• Primary intestinal lymphangiectasia
• Uso de gammaglobulina

• Capsule endoscopy
• Chromosome 4q25
• Chromosome deletion
• Double balloon enteroscopy
• Primary intestinal lymphangiectasia

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and “secondary” changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple’s disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn’s disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

• Intestinal lymphangiectasia
• Adults
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Adults
• Intestinal lymphangiectasia
• Submucosa

• Capsule Endoscopy
• Child
• Child, Preschool
• Dilatation, Pathologic
• Female
• Humans
• Immunoglobulin E/blood
• Lymphangiectasis, Intestinal/blood
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/pathology
• Lymphangiectasis, Intestinal/therapy
• Lymphatic Vessels/pathology
• Male
• Retrospective Studies

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

• Age Factors
• Diarrhea/diagnosis
• Diarrhea/diet therapy
• Diarrhea/pathology
• Diet, Fat-Restricted/methods
• Humans
• Lymphangiectasis, Intestinal/diagnosis
• Lymphangiectasis, Intestinal/diet therapy
• Lymphangiectasis, Intestinal/pathology
• Lymphedema/diagnosis
• Lymphedema/diet therapy
• Lymphedema/pathology
• Malabsorption Syndromes/diagnosis
• Malabsorption Syndromes/diet therapy
• Malabsorption Syndromes/pathology

Primary intestinal lymphangiectasia (PIL) 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. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.