Primary intestinal lymphangiectasia (ORPHA:90362)
A rare intestinal disease characterized by dilated intestinal lacteals which cause lymph leakage into the small bowel lumen. Clinical manifestations include edema related to hypoalbuminemia (protein-losing gastro-enteropathy), asthenia, moderate diarrhea, lymphedema, serous effusion and failure to thrive in children.
Epidemiology
Prevalence is unknown. Less than 500 cases have been reported worldwide.
Clinical description
Primary intestinal lymphangiectasia (PIL) is generally diagnosed before 3 years of age but may be diagnosed in older patients with very few symptoms. The main symptom is predominantly bilateral lower limb edema related to protein-losing enteropathy associated with hypoalbuminemia. Edema may be moderate (in foot, ankle, calf) to severe with anasarca and can be associated with pericarditis, ascites (chylous or not) or pleural effusion. Fatigue, abdominal pain, weight loss, inability to gain weight, failure to thrive in children, moderate diarrhea, fat-soluble vitamin deficiencies due to malabsorption or iron deficiency with moderate anemia may also be present. In some patients, limb lymphedema is associated with PIL and it is difficult to distinguish from edema. Stemmer's sign is an important element to confirm the diagnosis and also differentiate lymphedema from edema: it is impossible to lift and pinch the skin on the second toe basis because of skin-thickening as the result of fibrosis.
Etiology
The etiology remains unknown. Very rare familial cases of PIL have been reported.
Diagnostic methods
Exsudative enteropathy is confirmed by elevated 24-hour stool alpha-1 antitrypsin clearance. Diagnosis of PIL is confirmed by endoscopic observation of dilated intestinal lacteals with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful to visualize intestinal lymphangiectasia (localization, extent) when endoscopic findings are not conclusive. Characteristic biochemical findings related to lymph leakage into bowel lumen include lymphopenia, hypoalbuminemia, hypogammaglobulinemia, hypocalcemia, and hypocholesterolemia.
Differential diagnosis
The main differential diagnosis includes enteropathy-associated T-cell lymphoma, Whipple disease, Crohn disease, sarcoidosis, tuberculosis (with extrapulmonary involvement), systemic sclerosis, and constrictive pericarditis.
Management and treatment
A strictly 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 ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and prevent lacteal overloading. Octreotide has been effective in treating some PIL patients. 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. Albumin infusion is a symptomatic treatment proposed in patients with important serous effusion or uncomfortable lower limb edema. Repeated albumin infusions may be useful in reducing edema but their efficacy is transient. Repeated fat-soluble vitamin supplementation, particularly vitamin D, is required. A prolonged clinical and biological follow-up is recommended.
Prognosis
The prognosis varies. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease or in patients who follow a low-fat diet. PIL outcome may be poor or even life-threatening when voluminous serous effusion(s) (pleural, pericardial) spontaneously occur, after low-fat diet withdrawal, or in cases with malignant complications. So, several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, mid gut or ileum) or with extra-intestinal localizations have also been reported in PIL patients.

                            Last update: 
                            June 2019


                            - Expert reviewer(s): 
                            Dr Stéphane VIGNES