Background
Intestinal lymphangiectasia is a rare protein-losing gastroenteropathy characterized by impaired drainage of lymph from the small intestine, associated with dilatation of the intestinal lymphatic channels. This leads to inappropriate loss of lymph into the gastrointestinal (GI) tract, causing hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunologic dysfunction. [1]
Protein-losing gastroenteropathies have been classified into three groups (depending on the mechanism of their etiology) that include the following [2] : (1) inflammatory-induced mucosal erosions and/or ulcerations (eg, Crohn disease), (2) mucosal damage or abnormalities resulting in increased protein permeability without mucosal erosions or ulcerations (eg, celiac disease), and (3) protein loss stemming from mechanical lymphatic obstruction (eg, intestinal lymphangiectasia).
See protein-losing enteropathy for a more comprehensive discussion on this topic.
Pathophysiology
Protein-losing gastroenteropathy occurs when protein loss into the gastrointestinal (GI) tract exceeds the liver’s production capacity. Intestinal lymphangiectasia is defined by compromised enteric lymph drainage and the presence of dilated lymphatic channels. [3, 4] This condition is categorized into two types: primary and secondary intestinal lymphangiectasia.
Primary intestinal lymphangiectasis (PIL), also known as Waldmann disease, pertains to congenital anomalies. These malformations manifest as extensive or localized dilatations (ectasia) of enteric lymphatics, situated within the mucosa, submucosa, and/or subserosa layers of the intestine. Several genes associated with the development of the lymphatic system have been studied, but none have been conclusively identified as clinically significant contributors to PIL. [5]
Secondary intestinal lymphangiectasia typically results from obstruction. Cardiac diseases can give rise to secondary lymphangiectasia by elevating central venous pressure, subsequently hindering the drainage of the thoracic duct into the left subclavian vein. [6] These conditions encompass structural heart disease such as constrictive pericarditis and cardiomyopathy. Other potential causes of secondary intestinal lymphangiectasia include malignancy (eg, lymphoma), infection (eg, tuberculosis), inflammatory conditions (eg, sarcoidosis), blood clots (eg, mesenteric venous thrombosis), portal hypertension, retroperitoneal fibrosis, and enlargement of retroperitoneal lymph nodes. [7]
Serum proteins commonly impacted include albumin, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), ceruloplasmin, and fibrinogen. This results in immunologic abnormalities, leading to hypogammaglobulinemia, anergy, and impaired allograft rejection. Other serum constituents can also be lost, including iron, lipids, and trace elements, many of which are bound to proteins. [4]
Etiology
The following conditions can cause secondary intestinal lymphangiectasia:
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Abdominal or retroperitoneal carcinoma
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Cardiac disease (eg, constrictive pericarditis, congestive heart failure)
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Enteric-lymphatic fistula
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Hepatic venous outflow obstruction
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Malignancy involving mesenteric lymph nodes or lymphatics
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Mesenteric tuberculosis
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Mesenteric venous thrombosis
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Retroperitoneal lymph node enlargement
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Sclerosing mesenteritis
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Thoracic duct obstruction
Epidemiology
The incidence and prevalence of primary and secondary intestinal lymphangiectasia remains unknown due to rarity. [5]
There is no known racial predilection for this condition. [4] However, there is a male-to-female ratio of 3:2. Intestinal lymphangiectasia can be primary (congenital), typically impacting children and young adults with a mean age of onset at 11 years. In these cases, the diagnosis often occurs during the first decade of life, with initial symptoms such as persistent diarrhea and peripheral edema. Alternatively, this condition can be secondary to other disease states, affecting older adults. [1, 7] In a series from Japan, the average age at onset was 22.9 years.
Prognosis
The clinical course of intestinal lymphangiectasia is highly variable, with approximately 23% of patients experiencing improvement, 64% remaining unchanged, and a mortality rate of 13%.
In patients with primary intestinal lymphangiectasia, especially those with an early onset, which typically occurs during the first decade, growth retardation is a common concern due to malabsorption. [5] On the other hand, the prognosis of patients with secondary intestinal lymphangiectasia depends on the extent and severity of the underlying disease.
Morbidity/mortality
Morbidity in this disease is closely tied to its pathophysiology. Predominant clinical features include edema and diarrhea, but the condition is also associated with the following negative sequelae:
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Lymphocytopenia, hypogammaglobulinemia
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Hypoalbuminemia, hypocalcemia, trace metal deficiency
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Chylous pleural effusions, ascites (Chylous ascites and transudative ascites are reported.)
Complications
Primary intestinal lymphangiectasia is linked to an increased risk of lymphoma. [7] Patients with congenital intestinal lymphangiectasia have reported fibrotic entrapment of the small bowel. [8] Oral manifestations of this condition include gingivitis caused by poor lymphocytic function and enamel defects caused by inadequate calcium absorption. [9]
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Intestinal villi of normal height with dilated lymphatics as usually seen on histology of villi in intestinal lymphagiectasia.
