From edematous syndrome to the diagnosis of " intestinal lymphangiectasia " ( clinical observation of a rare disease )

Clinical case In 2007, the gastroenterological department of the Donetsk Regional Clinical Territorial Medical Union (DRCTMU) hospitalized patient L., 29 years old, which is when you receive a complain weight gain, swelling of the face, extremities, anterior abdominal wall weakness. Particular excitement patient caused weight gain without an apparent gain in appetite or a significant increase in the volume of food consumed over the past few months. By carefully observing the operation selection bodies, the patient is not marked tendency to constipation (intestinal emptying 1-2 times/day) and the appearance of pathological contaminants in the stool; also there were no visual changes in urine and dysuric complaints, and the volume of urine released during the day was about 1 liter.

Separately, we emphasize that the villi of the duodenum were not shortened, not thickened, enlarged lymphatic vessels and PAS-positive foamy macrophages were absent.
Based on the history of the disease, life, objective examination, the results of laboratoryinstrumental research, the following alleged clinical diagnosis is formulated: Main diagnosis: Edematous syndrome of unknown etiology. Concomitant diagnosis: Secondary hypochromic anemia?

Differential diagnosis
The absence of visible pathological abnormalities according to the ultrasound of various organs and systems in the presence of clinically significant edema caused a careful analysis of the results obtained and a logical exclusion of probable causes of edema. Our reasoning proceeded in the following direction. Swelling can occur with the following diseases (Table 1). When analyzing the probable causes of hypoproteinemic edema, the pathology of the liver, kidneys, and cachexia were quickly excluded, whereas for the elimination of enteropathy it was considered necessary to carry out capsular video endoscopy. Below is a description of the research and the conclusion of a physician of functional diagnostics who performed capsular video endoscopy (November 20, 2007, Fig. 2): "The mucous stomach is moderately focalized hyperemic. In the lumen of the stomach is the secretory contents without pathological impurities. Peristalsis of the stomach is uniform, its activity is slightly reduced. The folds of the jejunum are edematic, the villous tissue is preserved throughout, the intestinal mucosa has a colorful appearance due to the presence of multiple whitish spots 1-2 mm in size, located from the distal parts of the duodenum to the ileum. The wall of the small intestine is rigid, the peristalsis weakened, uneven due to the reduction or total absence of long peristaltic waves. The video capsule reached the initial section of the transverse colon. The mucosa of this part of the large intestine is pale pink, smooth, the submucosal vascular pattern is clearly contoured. Conclusion: exudative enteropathy".

Final diagnosis and tactics of patient management
The results of capsular video endoscopy allowed to establish the cause of edematous syndrome and the following way to transform the final diagnosis: Main diagnosis: Primary intestinal lymphangiectasia (Waldman's disease or exudative enteropathy) with pronounced edematous syndrome, hypoproteinemia and hypoalbuminemia, severe course.
The patient was prescribed albumin (intravenously), iron preparations (oral). In order to strengthen the intercellular contacts in the epithelium of the small intestine mucosa, we deemed it advisable to designate the octerotide and Essentiale forte N. The above therapy helped regress the edematous syndrome, significantly reduce weakness and body weight, increase the level of albumins and total protein, leveling the phenomena of hypochromic anemia.

Literature review Brief historical information
In 1961, Waldman et al. described 18 cases of "idiopathic hypercatabolic hypoproteinemia": in the patients examined there were pronounced edemas that were associated with hypoproteinemia, hypoalbuminemia, and a decrease in γ-globulin concentration [2][3][4][5][6]. Researchers recorded a marked decrease in the total protein reserve determined with labeled 131I-albumin. In the course of a microscopic examination of the biopsy specimens of the small intestine, dilatation of the lymphatic vessels in the mucous, submucosal and serous layer of varying severity was revealed. To describe the discovered pathology, scientists suggested using the new term "intestinal lymphangiectasia" (IL) [2][3][4][5][6].

Epidemiology
The prevalence of clinically manifested IL is not known exactly [2][3][4][5][6]. It should be noted that IL can be asymptomatic, affect children, adolescents, adults. In the medical literature, single cases of the family form of Waldman's disease are described [2,4].

Etiology
The causes of IL are currently not known exactly [2][3][4][5][6]. It has been established that exudative enteropathy can complicate the course of various diseases ( Table 2). Sometimes the course of the disease is accompanied by the appearance of diarrhea, malabsorption syndrome, mechanical obstruction of the small intestine (due to local edema leading to thickening and contraction of the intestinal wall). Patients with IL often suffer from celiac disease, have concomitant iron deficiency and anemia, rarely suffer from recurrent hemolytic uremic syndrome, osteomalacia [2][3][4][5][6]. In some cases, IL can manifest with recurrent gastrointestinal bleeding.

Diagnostics
IL is confirmed by the detection of intestinal lymphangiectasia according to the histological examination of the biopsy specimen obtained during endoscopic examination of the small intestine [2][3][4][5][6]. Macroscopically, IL is characterized by a gently creamy, almost yellow staining of the villi in combination with a significant dilatation of the lymphatic vessels. The density of lymphangiectasia and its size varies from several mm to several cm. Histological examination of biopsy specimens of the duodenum and jejunum confirms the presence of lymph, dilated lymphatic vessels in the mucosa, submucosa, serosa and the presence of polyclonal plasma cells. With IL can be changed (dilatation) set or only a few intestinal lymphatic vessels. In the case of segmental or local lymphatic vascular lesions, upper endoscopy can give negative results, in such cases it is advisable to conduct video-video endoscopy, which has the maximum specificity in diagnosis of IL, regardless of its localization [2][3][4][5][6].

Complications
The course of the disease can be complicated by the development of neoplasia, the highest likelihood of lymphoma: the time interval from the diagnosis of IL to the development of lymphoma is 39-40 years. As a rule, lymphomas are localized in the gastrointestinal tract (stomach, small intestine). Lymphoma, in turn, can cause secondary IL [2][3][4]6].

Treatment
Patients with IL are recommended to follow a diet with a low fat content [2][3][4]6]. Previously, anti-plasmin inhibitors have been used in the treatment of IL (several studies have documented a positive effect of tranexamic acid at a dose of 1 g 3 times/day); scientists explained this fact by improving the permeability of lymphatic vessels against the background of increased fibrinolysis. At present, octreotide is widely used for the treatment of IL (sandostatin 150-200 μg 2 times/day subcutaneously), which allows achieving clinical, biochemical and histological improvement [2][3][4]6]. The mechanism of action of the somatostatin analogue on the gastrointestinal tract remains unclear. It is suggested that octerotide induces short-term vasoconstriction of internal organs, including lymphatic vessels, and also inhibits the absorption of triglycerides, which leads to a significant clinical effect.
In some cases, with secondary IL (in patients with inflammatory bowel diseases) corticosteroids are prescribed [2][3][4]6]. Symptomatic therapy includes albumin infusions, this type of therapy is used in severe disease [2][3][4]6]. Some authors consider it expedient to perform surgical intervention in case of segmental or local involvement of the small intestine.

Prognosis
The prognosis for IL depends on the underlying disease: in primary IL it is unfavorable, at secondary IL it depends on the underlying disease that caused its appearance.
Currently, the contact with the patient is lost (the patient has changed her residence), so how did her fate develop in the future, and whether the disease progressed is not known.
In conclusion, we give the basic data on intestinal lymphangiectasia, which are presented in this article (Table 3). Table 3 Key provisions Expressed peripheral edema combined with hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia or lymphocytopenia are typical manifestations of IL. To confirm the diagnosis, a histological examination of the small intestine biopsy obtained during upper endoscopy or video-endoscopy is necessary. For successful treatment of IL it is necessary to observe a diet with a low fat content, symptomatic therapy (administration of albumins, correction of electrolyte disorders), administration of octreotide, if necessary, corticosteroids. The prognosis for primary IL is unfavorable.