PIL is caused by a variety of causes of lymphatic flow obstruction, resulting in dilatation and rupture of the lymphatic ducts of the small intestine, and leakage of lymphatic fluid. Lymphatic vessels of the small intestine are distributed in the lamina propria, submucosa, and serosal layer. They return to the blood circulation through the chylomicron and the thoracic ducts. When the lymphatic flow is blocked, the lymphatic pressure rises, expands, and ruptures. As a result, the protein, fat, and lymphocytes contained in the fluid leak into the lumen of the intestine or are lost from the abdominal cavity. Clinical manifestations such as hypoproteinemia, steatorrhea, and reduction in lymphocyte count may occur with it. In addition, PIL may present with a broad spectrum of clinical manifestations, including edema, ascites, moderate diarrhea, pleural effusion, lymphedema, abdominal pain, weight loss and fat-soluble vitamin deficiencies [6].
PIL is largely responsible for lymphatic leakage into the intestinal lumen, which leads to edema, lymphopenia and hypoalbuminemia [15]. Edema and diarrhea are usually the main clinical manifestations. Edema is of pitting type, and usually bilateral and symmetrical in distribution involving the upper and lower limb, face, scrotum or vagina [6–7]. Lymphedema is a rare disorder which may be associated with intestinal lymphangiectasia [8], and is not easy to regress as the abnormality may be persistent [9–10]. And also there may be hypogammaglobulinemia with low levels of IgA, IgM and IgG, low counts of CD4 and lymphocytes [12].
To date, the pathogenesis of PIL is not yet clear. Therefore, it has brought serious difficulties for our diagnosis. Because clinical manifestations of PIL are similar to many diseases, it is often misdiagnosed as other diseases. At present, there is no uniform standard for diagnosing PIL in children. The diagnosis of small intestine lymphatic ectasia is mainly based on clinical manifestations, biochemical indicators, imaging examinations, and biopsy, of which the biopsy is considered as the gold standard of the disease.
When children have edema, diarrhea, hypoproteinemia and other clinical manifestations, and the general treatment is invalid, then PIL should be considered. In order to confirm the hypothesis, we usually use endoscopy to obtain tissue biopsy to further confirm the diagnosis. For the diagnosis of PIL in children, endoscopic methods including gastroscopy, duodenoscopy, double-balloon enteroscopy, and capsule endoscopy are commonly used. It is usually determined by the condition of the hospital and the wishes of the patient for which endoscopy method is chosen. In our previous study, we found that the diagnostic rate of gastroscopy in PIL can be as high as 86% [8]. The mucosa of the small intestine of duodenal proximal segment is often swollen and hypertrophied, with yellow or snow-like protrusions on the surface, and even intestinal stenosis through the gastroscopy. In our study, gastroscopy was used in 8/10 of the patients. When the lesion occurs in the small intestine, capsule endoscopy can be used to observe changes in the intestinal mucosa [16]. In recent years, the prevalence of PIL has increased with the development of capsule endoscopy. The clear image of the lesioned bowel surface and complete examination shown by capsule endoscopy has a good diagnostic value for PIL, which is the extent that general endoscopy cannot achieve [17–19]. Unfortunately, the disadvantage of capsule endoscopy is that it cannot obtain biopsy for pathological diagnosis. If possible, capsule endoscopes can be used in combination with double-balloon enteroscopy, which can obtain biopsy for pathological diagnosis [17, 20]. Due to limited conditions, only 40% of children in this study used capsule endoscopy to observe changes in the intestinal mucosa.
At present, in addition to endoscopy, there are many other non-invasive methods, including 24 h stool alfa-1-antitrypsin clearance,99Tc-HSA,lymphoscintigraphy, ultrasonography (USG),computed tomography (CT) scan, and magnetic resonance imaging(MRI) for diagnosing PIL. Although these inspection methods all have non-invasive advantages, they also have various disadvantages, such as high cost, complicated operation, infections risk and so on [21].
Come so far, there is still a lack of uniform and standardized treatment methods for PIL. Medical conservative treatment and surgical treatment are currently two commonly used methods. In general, the therapeutic goals are to improve the clinical symptoms of children, increase serum protein levels, promote weight gain through nutrition interventions, and ensure children's growth and development.
Once diagnosed with PIL, the MCT diet therapy (low in long chain fatty acids, high in protein and medium chain triglycerides) is usually given first[22–24]. The fat in the natural diet consists mainly of LCT, and is absorbed in the form of chylomicrons through the lymphatic circulation. In contrast, MCT can be directly absorbed into the blood through the hepatic portal vein. As MCT does not enter the lymphatic circulation, it can reduce the production of lymph, which can relieve the pressure of the lymphatic lumen of the capillaries, and ultimately prevent the leakage of the lymph to reduce the intestinal protein loss[25–26]. For patients who have not yet added complementary food, formulas which are rich in MCT should be used. In our study, formulas with medium chain fatty acids accounting for 60% of total fat were given to the patients. For older children (> 6 months), MCT oil can be used to cook food on the basis of formula being rich in MCT.
When the clinical symptoms are severe and dietary therapy is restricted, parenteral nutrition (PN), infusion of albumin and diuretics can be used in combination with MCT diet, which will achieve good results. In our study, most patients received parenteral nutrition and fat free (or low fat) diet at the beginning of treatment. After a positive symptomatic treatment, the gastrointestinal symptoms improved and the MCT diet was given. The clinical symptoms of the children were all significantly less than before. Patient 4 was given the regular diet because of no gastrointestinal manifestations.
When the child is insensitive to those treatments, other options can be considered or in conjunction with the MCT diet. These are corticosteroids, octreotide, and antiplasmin (tranexamic acid) [27–28], which play important roles in Anti-inflammation [27, 29], decreasing absorption of triglycerides and reduces clinical manifestations [27, 30], and improving lymphatic permeability to proteins respectively [31–32].
When medical treatment is not satisfactory, and serious complications, such as uncontrolled bleeding from gastrointestinal ulcers or refractory mechanical obstruction resulting from severe focal bowel wall edema occur, surgical treatment may be considered [33–34]. However, since the lymphatic dilatation of the small intestine is diffuse, surgical treatment is often not the preferred method. Surgical resection of segmental or locally expanding bowel is the recommended surgical procedure [35]. The key to success in surgery is not to cause short bowel syndrome, but also to completely remove the diseased bowel. Most of them still need to adhere to MCT dietary therapy and/or PN after surgery.