Lymphangiectasia is a condition wherein the lymphatics are dilated. The result is that lymph channels may become blocked and there is a "leakage" of fluid into the affected body area. (It is also associated with lymphedema. See below list of complications)
Signs and symptoms
Symptoms include diarrhea, nausea, vomiting, fatty stools, and abdominal pain may be present. Other indicators may include edema, low protein levels (caused from the protein loss from the condition), and low albumin levels.
Malformation or dilation of lymphatic channels resulting in lymph blockages and accumulation of fluids in the affected body areas.
This condition can either be primary (hereditary), primary (congenital) or can be secondary as a result of cancers, cardiac conditions, chronic inflammations, tuberculosis, scleroderma, lupus, fibrosis, endometriosis as well as other factors.
There is no cure for lymphangiectasia. Treatment is focused on control of complications, control through dietary habits and possible drug therapy for various symptoms. In the case of secondary lymphangiectasia treatment also focuses on the underlying cause.
...............................................Primary intestinal lymphangiectasia causing severe weight loss: CT, MR and histologic findings
Ianaccone R, Pietropaolo A, Marin D, Celestre M, Pasqualini V
|Age: 22 year(s)
|Clinical History and Imaging|
The patient presented with a 2-year history of marked weight loss (approximately 16 kg), lower extremity edema, stipsis, and intermittent episodes of colicky abdominal pain followed by steatorrhea. Results of laboratory studies showed hypoalbuminemia, hypogammaglobulinemia, and lymphocytopenia. A 24 h fecal fat collection showed loss of 16 g of fat.
Small bowel follow-through, not shown, revealed slight dilatation of the duodenum and small bowel and minimal thickening of the mucosal folds.
CT of the abdomen and pelvis was performed using a
multidetector-row helical scanner and revealed dilatation of the small
bowel due to increased fluid content associated with thickening and
hypervascularity of the mucosal folds (Fig. 1). There was no paraaortic
adenopathy and no abnormality at the level of the liver and
Small bowel biopsy revealed dilatation of lymphatics within the villi, consistent with the diagnosis of intestinal lymphangiectasia (Fig. 3). The patient was subsequently placed on a protein-rich, low-fat diet supplemented with medium-chain triglycerides with gradual increase of body weight.
Primary Intestinal Lymphangiectasia (PIL) is a rare congenital disorder characterized by abnormally dilated lymphatics located primarily in the small bowel wall. This results in severe leakage of lymph into the gastrointestinal tract which translates into loss of proteins, immunoglobulins, and lymphocytes. Common laboratory findings of PIL are: hypoalbuminemia, hypogammaglobulinemia, lymphocytopenia, and steatorrhea. The major clinical findings of PIL may include: protein-losing enteropathy, secondary edema, chylous ascites, pleural effusions, and abdominal pain.
PIL is usually a diagnosis of exclusion, taking into account the wide variety of pathologic conditions which may be associated with intestinal lymphangiectasia (i.e. secondary forms of the disease), including Crohn disease, Whipple disease, celiac disease, sarcoidosis, amyloidosis, tuberculosis, lymphoma, retroperitoneal tumors, Budd-Chiari syndrome, Systemic Lupus Erythematosus, chronic congestive heart failure, and constrictive pericarditis.
Although the evaluation of patient’s clinical history is often sufficient to rule out some of such secondary forms of intestinal lymphangiectasia, radiological studies are of great value in the achievement of the final diagnosis.
Small bowel follow-through is often the initial examination performed. Typical findings include small bowel dilatation, diffusely thickened mucosal folds, as well as haziness of the barium colon due to increased secretions.
CT and MR can play an important role in suggesting the diagnosis and discriminating many secondary forms of intestinal lymphangectasia. MRI can also provide information on the characteristics of the fluid content in the small bowel (hyperintense on T1-w images because of the high concentration of protein and/or lipid). The absence of ionizing radiation makes MRI more suitable than CT in the follow-up of patients with PIL.
Small bowel biopsy is still necessary to make the definitive diagnosis.
Primary Intestinal Lymphangectasia (PIL)
|MESH = A03.492.411.620.484 C15.604.360|
**Link no longer available**
Successful resection of localized intestinal lymphangiectasia post-Fontan: role of [sup.99m]technetium-dextran scintigraphy
Intestinal lymphangiectasia is a well-recognized complication of the Fontan procedure, occurring in up to 24% of patients. Because of the loss of chylous fluid into the gut lumen, protein-losing enteropathy results as well as lymphopenia and hypogammaglobulinaemia. In some cases, dilated lymphatics in the intestinal serosa or mesentery also rupture, causing chylous ascites. Standard medical and cardiac surgical interventions are generally ineffective and the condition is frequently lethal. We report a case of intractable and life-threatening chylous ascites and chylothorax in a 14-year-old girl, associated with intestinal lymphangiectasia and protein-losing enteropathy after a Fontan procedure for tricuspid atresia. The condition was refractory to all standard medical therapies, including dietary modifications, diuretics, corticosteroid therapy, albumin infusions, octreotide, heparin, bowel rest, and parenteral nutrition. Cardiac surgery to optimize her hemodynamic status was also ineffective and large volume pleural and ascitic fluid losses continued. Having exhausted all other therapeutic modalities, [sup.99m]technetium-dextran scintigraphy was performed to assess the extent of intestinal protein loss and the potential for surgical intervention. Scintigraphy suggested localized protein loss from the proximal jejunum and subsequent segmental resection was effective. Postoperatively, ascites and pleural effusions resolved, and there was no evidence of short bowel syndrome. Growth has accelerated and the patient has entered puberty. There is mild persistent intestinal protein loss requiring diuretic therapy. Ascites or pleural effusions are absent, and the patient remains well >2 years after surgery. Intestinal lymphangiectasia post-Fontan procedures has traditionally been ascribed to hemodynamic factors such as raised systemic venous pressure, which would predispose to a generalized intestinal lesion. However, in this case, scintigraphy demonstrated a localized, surgically correctible lesion. To our knowledge, this is the first reported case of the use of [sup.99m]technetium-dextran scintigraphy for this indication and of successful partial small bowel resection in such a case. Pediatrics 2003;112:e242-e247. URL: http://www. pediatrics.org/cgi/content/full/112/3/e242, intestinal lymphangiectasia, resection, Fontan procedure, [sup.99m]technetium-dextran, scintigraphy.
**Link no longer available**
A Case of Protein-Losing Enteropathy Caused by Intestinal Lymphangiectasia in a Preterm Infant
Intestinal lymphangiectasia is characterized by obstruction of lymph drainage from the small intestine and lacteal dilation that distorts the villus architecture. Lymphatic vessel obstruction and elevated intestinal lymphatic pressure in turn cause lymphatic leakage into the intestinal lumen, thus resulting in malabsorption and protein-losing enteropathy. Intestinal lymphangiectasia can be congenital or secondary to a disease that blocks intestinal lymph drainage. We describe the first case of intestinal lymphangiectasia in a premature infant. The infant presented with peripheral edema and low serum albumin; high fecal concentration of a1-antitrypsin documented intestinal protein loss. Endoscopy showed white opaque spots on the duodenal mucosa, which indicates dilated lacteal vessels. Histology confirmed dilated lacteals and also showed villus blunting. A formula containing a high concentration of medium chain triglycerides resulted in a rapid clinical improvement and normalization of biochemical variables. These features should alert neonatologists to the possibility of intestinal lymphangiectasia in newborns with hypoalbuminemia and peripheral edema. The intestinal tract should be examined for enteric protein losses if other causes (ie, malnutrition and protein loss from other sites) are excluded. The diagnosis rests on jejunal biopsy demonstrating dilated lymphatic lacteal vessels.Key words: hypoalbuminemia, lymphangiectasia, protein-losing enteropathy, preterm infant.
Protein-losing gastroenteropathy (PLGE) includes a large group of diseases characterized by enteric loss of plasma proteins in abnormal amounts.1 In most instances, PLGE is caused by enhanced mucosal permeability to proteins consequent to cell damage, mucosal erosions or ulcerations, and lymphatic obstruction. Protein-losing gastroenteropathy includes nonulcerative diseases (eosinophil gastroenteritis and Menetrier's disease); ulcerative diseases (erosive gastritis and inflamed bowel disease); and disorders resulting from lymphatic obstruction (congenital intestinal lymphangiectasia and Whipple's disease).
Intestinal lymphangiectasia is characterized by obstruction of lymph drainage from the small intestine and dilated lacteal vessels that distort the villus architecture. It is often observed in adults and older children; it has been described prenatally and in 2 full-term siblings.2,3 There are no previous reports of this entity in premature infants.
This infant boy, born at 30 weeks gestation and weighing 1210 g, had hyaline membrane disease and grade II intraventricular cerebral hemorrhage during the first days of life. He was admitted to the neonatal intensive care unit and given expressed breast milk and a formula for preterm infants (Similac Special Care Formula, Ross Laboratories, Columbus, OH). He developed edema on the legs and head during the first week of life. Concentrations of serum albumin (2.0 g/dL), immunoglobulin G (IgG) (324 mg/dL), and transferrin were low. Serum immunoglobulin A (IgA) (6.2 mg/dL) and immunoglobulin M (IgM) concentrations were normal. Blood cell count excluded lymphocytopenia. Proteinuria, inadequate protein intake, and liver and heart diseases were excluded. High a1-antitrypsin stool levels (>3 mg/g dry-weight sample) and fecal a1-antitrypsin clearance (65 mL/die) indicated enteric loss of plasma proteins. Upper intestinal endoscopy, performed with a neonatal fiberscope (5.5 mm diameter; Olympus, Turin, Italy), without sedation showed white opaque spots on the duodenum mucosa, and 2 biopsies were taken from the areas most affected. Duodenal histology showed a distorted villus profile attributable to dilated lymphatic channels and areas of villus blunting intermingled with seemingly normal areas (Fig 1). The esophageal and gastric mucosa appeared histologically normal. Ultrasound examination of the heart and abdomen excluded secondary causes of lymphangiectasia (ie, chronic congestive heart failure, constrictive pericarditis, pericardial effusion, abdominal masses, and intestinal malrotation). The final diagnosis was congenital intestinal lymphangiectasia.
Breast milk and adapted formula were replaced by a formula with a high concentration of medium chain triglycerides (Portagen, Mead Johnson Nutritionals, Rome, Italy), which caused a rapid clinical improvement. At follow-up, the serum albumin level had increased remarkably (3.1-3.8 g/dL) and a1-antitrypsin stool levels were normal; edema had regressed and the infant had gained weight. When the infant was 6 months old, beikost and medium chain triglycerides were introduced as the sole sources of fat in his diet. At present, the infant is 1 year old and is growing well.
Intestinal lymphangiectasia is characterized by obstruction of the intestinal lymphatic vessels and increased lymphatic pressure that cause PLGE and malabsorption of chylomicrons and fat-soluble vitamins. Intestinal lymphangiectasia is a primary disorder in cases of malformation of lymphatic vessels at intestinal level or in other areas of the body. It can also occur secondary to diseases that cause intestinal lymphatic obstruction, eg, abdominal or retroperitoneal tumors, retroperitoneal fibrosis, chronic pancreatitis, mesenteric tuberculosis, Crohn's disease, intestinal malrotation, Whipple's disease, celiac disease, constrictive pericarditis, and chronic congestive heart failure.1,4,5
We describe the first case of intestinal lymphangiectasia in a preterm infant. This entity is rarely suspected in the differential diagnosis of a tiny newborn with peripheral edema and hypoalbuminemia. These features should alert pediatricians to the possibility of enteric loss of proteins if other causes, such as malnutrition and hepatic and renal diseases, are excluded. In our case, an excessive concentration of a1-antitrypsin measured in random dry stool and the high plasma clearance of a1-antitrypsin demonstrated an abnormal enteric loss of proteins. In earlier studies, both tests have detected abnormal enteric loss of proteins.6,7 Differently, radioactive methods, including intravenous administration of 51Cr albumin or 51Cr chloride, are cumbersome and expensive, and are rarely used because radioactive macromolecules are not widely available.
Although lymphocytopenia is supposedly a marker of intestinal lymphatic channel obstruction, it was not found in our patient. This coincides with reports that lymphopenia was not present during the early phases of intestinal lymphangiectasia in young children.2,3 Furthermore, drainage of lymphocytes through the lamina propria can be unremarkable in the absence of inflammatory activation in the intestinal mucosa.3
Endoscopy of the upper intestinal tract was crucial in establishing the diagnosis of intestinal lymphangiectasia. In fact, white opaque spots detected on the duodenal mucosa and biopsies sampled during endoscopy showed dilated lymphatic channels. Because the mucosal lesions in intestinal lymphangiectasia are often patchy and localized, endoscopy is an aid to selecting regions for biopsy. Differently, multiple mucosal biopsies may be necessary if peroral jejunal sampling is used.8 In our case, ultrasound excluded other causes of lymphatic obstruction and excessive protein efflux into the intestinal tract, eg, constrictive pericarditis, pericardial effusion, superior vena cava obstruction, heart failure, intestinal malrotation, and intestinal tumors.
In summary, although intestinal lymphangiectasia primarily affects children and young adults, it should be included in the diagnostic work-up in preterm infants presenting with peripheral edema and hypoproteinemia when there is excessive enteric protein loss. An early diagnosis of intestinal lymphangiectasia in newborns and small infants may prevent such severe complications as lymphocytopenia and malnutrition. Endoscopy can be successfully performed even in preterm neonates to explore the upper gastrointestinal mucosa.
We thank Jean Ann Gilder for editing the text.
Gastrointestinal Endoscopy and Motility Unit - * Neonatal Intensive Care Unit - Department of Pediatrics - University of Naples, "Federico II'
Via Sergio Pansini 5, I-80131, Naples, Italy
Waldmann Disease is a rare digestive disorder characterized by abnormally enlarged (dilatation) lymph vessels supplying the lining (lamina propria) of the small intestine. The main symptoms are abdominal discomfort and swelling of the limbs. The disorder may be present at birth (congenital) or acquired.
LYMPHANGIECTASIA, INTESTINAL - Online Mendelian Inheritance In Man
Homburger and Petermann (1949) described a disorder, which they called 'familial idiopathic dysproteinemia,' characterized by edema of the legs, with ulcers in the males and 'functional vascular changes' in the females; dysproteinemia of variable type, sometimes discernible only by electrophoresis; a number of congenital malformations; and a high incidence of stillbirths. Persons in 3 generations were affected and male-to-male transmission occurred. Subsequently these patients were found to have intestinal loss of protein, presumably because of lymphangiectasia (Waldmann et al., 1961; Waldmann and Schwab, 1965). Murphy (1972) gave clinical follow-up. Lymphopenia due to exaggerated intestinal loss is also a feature. Double vortex pilorum ('hair whorl') and usually prominent 'floating ribs' (ribs 11 and 12) were present. Parfitt (1966) described 3 sibs (2 females, 1 male) affected out of 5. All had neonatal edema. The small bowel showed dilated lymphatic spaces and partial villous atrophy. Cottom et al. (1961) reported neonatal hypoproteinemia in 2 sibs, and other probable cases are known. See also hereditary lymphedema I (153100) and protein-losing enteropathy (226300). Patients with intestinal lymphangiectasia have hypogammaglobulinemia, lymphocytopenia, skin anergy and impaired allograft rejection. Peripheral blood lymphocytes show impaired in vitro blastic transformation (Weiden et al., 1972). This is attributable to depletion of lymphocytes necessary for transformation. The situation is comparable to experimental thoracic duct drainage.
Primary intestinal lymphangiectasia (Waldmann's disease)
1Department of Lymphology, Centre de référence des maladies vasculaires rares, Hôpital Cognacq-Jay, 15, rue Eugène Millon, 75015 Paris, France
2Department of Gastroenterology and Nutrition, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
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.
Disease name and synonyms
Primary intestinal lymphangiectasia (PIL).
History and definition
In 1961, Waldmann et al. described the first 18 cases of "idiopathic hypercatabolic hypoproteinemia" . These patients had edema associated with hypoproteinemia, low serum albumin and gammaglobulin levels. The total exchangeable albumin pool, assessed with radio-labeled 131I-albumin, was low in all patients. Daily fecal excretion of 131I was twice the highest value obtained in controls. Microscope examination of the small intestine biopsies showed variable degrees of dilation of the lymph vessels in the mucosa and submucosa. The authors also proposed the term "intestinal lymphangiectasia".
The prevalence of clinically overt PIL is unknown. However, PIL can be asymptomatic; it primarily affects children (generally diagnosed before 3 years of age) and young adults but may be diagnosed later in adults[2,3]. Very rare familial forms of Waldmann's disease have been reported
Peripheral edema of variable degree, usually symmetrical, from moderate (lower limb edema) to severe, including the face and external genitalia, is the main clinical feature, which accounts for 95% of PIL clinical manifestations. Moderate serous effusions (pleural effusion, pericarditis, chylous ascites) are common, and life-threatening anasarca may occur rarely throughout the course of the disease [1,5]. The edema is pitting because the oncotic pressure is low due to hypoalbuminemia resulting from exsudative enteropathy. PIL may be suspected at birth or during pregnancy based on ultrasonography images, which can detect fetal ascites or lower limb lymphedema .
In children, PIL is generally diagnosed before 3 years of age [5,7,8] and may be complicated by fatigue, abdominal pain, nausea, vomiting and weight loss, inability to gain weight and growth retardation. Malabsorption may cause fat-soluble vitamin deficiencies and hypocalcemia leading to convulsions.
- Lymphedema is a rare disorder which is usually not associated with another disease, but it may be associated with intestinal lymphangiectasia. Clinical features of lymphedema are specific (Figure 1). Lymphedema is less pitting than edema due to hypoproteinemia, and is localized to the lower limbs (foot, ankle, calf, rarely thigh) and predominantly bilateral. Upper limb with hand and forearm involvement, lymphedema of breast and external genitalia (with skin thickening) may also be present . In most patients with lymphedema, edema as a consequence of hypoproprotidemia has also been observed. The two types of edema are not always easily distinguished. Stemmer's sign is an important element to confirm the diagnosis and differentiate lymphedema from edema: i.e., it is impossible to lift and wrinkle the dorsal skin on the second toe because of skin-thickening as the result of fibrosis
Moderate or discontinuous diarrhea is the main digestive symptom .
- An abdominal mass was found in the epigastrium and right upper quadrant of a 12-year-old girl. Ultrasonography failed to confirm an abdominal mass but the mass was attributed to small bowel edema .
- A malabsorption syndrome may be encountered in the elderly .
- Mechanical ileus of the small intestine caused by localized edema leading to intestinal wall-thickening and lumen diminution. It may be visualized as a segmental mass requiring resection (histological findings: dilation of submucosal lymphatics, extensive pseudocysts in the jejunal wall, intramural lymph edema, secondary bleeding, tight stenosis of the jejunal lumen) .
- Chylous reflux into the skin of the right flank resembles lymphangioma circumscriptum with multiple dome-shaped vesicles filled with milky-white fluid, which is discharged into the surrounding skin .
- Chyle can also backflow into the skin of the lower limb, perineum or external genitalia .
- An association with celiac disease has been reported in children .
- Iron deficiency with anemia occurs secondary to chronic blood loss resulting from non-specific multiple ulcers in the small intestine .
- Necrolytic migratory erythema can be seen .
- Recurrent hemolytic uremic syndrome has been described.
- Osteomalacia resulting from vitamin D deficiency was reported in a 63-year-old woman .
- It remains open to debate whether recurrent gastrointestinal bleeding is indeed a manifestation of PIL .
First described in 1964 by Samman and White, the yellow nail syndrome is a very rare condition which may be associated with PIL. Dystrophic yellow nails with ridging and loss of lunula on the hands are associated with lymphedema and pleural effusions .
Five syndromes are associated with intestinal lymphangiectasia: von Recklinghausen, Turner (X0) or Noonan, Klippel-Trenaunay and Hennekam . In general, these syndromes are easily distinguishable by the presence of facial abnormalities (Turner, Noonan, Hennekam), mental retardation (Hennekam, Noonan), seizures (Hennekam), severe limb and/or face lymphedema (Hennekam), neurofibromas and other tumors (von Recklinghausen), and hemihypertophy of the limbs associated with vascular malformations (Klippel-Trenaunay).
To date, PIL etiology is unknown. Intestinal lymphangiectasia is responsible for lymph leakage into the bowel lumen, which leads to hypoalbuminemia and lymphopenia. Edema is the consequence of hypoprotidemia with decreased oncotic pressure. Several genes, such as VEGFR3 (vascular endothelial growth factor receptor 3), prospero-related homeobox-transcriptional factor PROX1, forkhead transcriptional factor FOXC2 and SOX18 are implicated in the development of the lymphatic system. In a recent paper, Hokari et al. reported inconsistently changed expressions of regulatory molecules for lymphangiogenesis in the duodenal mucosa of PIL patients.
PIL diagnosis is confirmed by the presence of intestinal lymphangiectasia based on endoscopic findings with the corresponding histology of intestinal biopsy specimens (Figure 2). Macroscopic abnormalities are usually obvious with creamy yellow of jejunal villi corresponding to marked dilation of the lymphatics within the intestinal mucosa. The density of lymphangiectasia varies and their size ranges from mm to cm. Histological examination of duodenum-jejunum and ileum biopsies confirms the presence of lacteal juice, dilated mucosal (from moderate to severe) and submucosal lymphatic vessels (and also in the serosa) with polyclonal normal plasma cells. Intestinal lymphatics may be dilated in many villi or only a few. Intestinal abnormalities may be slight; small bowel mucosa also appears edematous but not creamy. That neither villous atrophy nor microorganisms are found in biopsies is underlined in pathology reports. Endoscopy may be negative when intestinal lesions are segmental or localized. In such cases, videocapsule endoscopy, easier to use than enteroscopy, is a useful tool to detect the presence of intestinal lymphangiectasia and to specify its localization (Figure 3) [25-27]. Videocapsule endoscopy is also feasible to appreciate the extent of lymphangiectasia in children.
Indirect biological abnormalities are suggesting of PIL, such as hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia with low IgG, IgA and IgM levels or lymphocytopenia. Exsudative enteropathy is confirmed by the high 24-h stool α1-antitrypsin clearance due to enteric protein loss. Functional absorption tests, e.g., such as D-xylose test results are normal in PIL.
Although various methods have been proposed to investigate PIL, none of them can replace histological examination of biopsies to confirm the diagnosis.
99mTechnetium-labeled human serum albumin (99mTc-HSA) scintigraphy may show marked enhancement in the bowel, which indicates protein leakage into this region. Serial scanning for up to 24 h is required to detect protein loss from the gut, perhaps because of the intermittent nature of protein loss. 99mTc-HSA scintigraphy has high sensitivity and is able to identify the site of protein loss (large and/or small bowel localization, stomach) . The α1-antitrypsin method has replaced 99mTc-HSA scintigraphy, which is more costly, less readily available and also uses a human product potentially carrying an infectious risk.
Indirect features may suggest PIL in children and adults. Ultrasonographic findings may show dilation of the intestinal loops, regular and diffuse thickening of the walls, plical hypertrophy and severe mesenteric edema and, in some cases, ascites [30,31].
Axial abdominal CT images are obtained with oral and intravenous contrast medium enhancement. CT appearance of PIL is similar in adults and children. Typically, there is diffuse, nodular, small bowel wall-thickening and edema, which are a consequence of the dilated lymphatics within the villi, along with some degree of small bowel dilation, with, in few cases, a "halo sign" due to swelling and edema [32-34]. CT may be useful to identify localized intestinal lymphangiectasia .
Lymphoscintigraphy is an effective tool for identifying abnormal lymphatic tree in the upper or lower limb and also to confirm limb lymphedema, when the limb images are abnormal. In limb lymphedema, isotope-uptake seen on the lymphogram shows an absence of visible lymph nodes which indicates either peripheral lymphatic obliteration or inability of the vessels to transport lymph up the limb through incompetent lymphatic vessels . 99mTc-radio-labeled rhenium sulfur colloid and albumin colloid are the two isotopes currently used in limb lymphoscintigraphy. At present, lymphoscintigraphy is not a routine and useful methodology for PIL diagnosis. Indeed, in one study, So et al. reported that intestinal lymphoscintigraphy (after subcutaneous injection of 99mTc-antimony sulfide colloid into the two first toe spaces) only detected the presence of radioactivity in less than half of patients with histologically proven PIL .
PIL patients have immunological abnormalities involving both the B-cell and T-cell lineages of the immune system. The B-cell defect is characterized by low immunoglobulin levels (IgG, IgA and IgM) and poor antibody responses [38-40]. The T-cell defect is characterized by lymphocytopenia, prolonged skin-allograft rejection and impaired in vitro proliferative responses to various stimulants (anti-CD3, anti-CD28) . Furthermore, PIL patient's peripheral blood samples contain extremely low counts of CD4+ T cells, especially naïve, CD45RA+ CD62L+, while CD45RO+ memory cells, are only moderately below normal. CD45RA+ and CD45RO+ CD8+ T cells are moderately below normal .Differential diagnosis
The differential diagnosis is of special importance for subjects suspected of having PIL. Some secondary causes of intestinal lymphangiectasia have been identified as diseases responsible for anatomical or dynamic alterations of the lymphatic flow. Protein-losing enteropathies associated with intestinal lymphangiectasia may arise secondary to constrictive pericarditis [42-44], intestinal lymphoma [45,46], lymphenteric fistula , Whipple's disease , Crohn's disease , sarcoidosis , intestinal tuberculosis , systemic sclerosis , radiation and/or chemotherapy with retroperitoneal fibrosis, human immunodeficiency virus-related enteropathy  or the Fontan operation to treat cardiac malformations .
Many diseases are associated with excessive enteric loss of plasma proteins but do not include lymphatic lymphangiectasia, such as Menetrier's disease or inflammatory states of systemic lupus erythematosus in adults and children [56-59].Complications
It is not clear whether the occurrence of malignancy, especially lymphomas, is fortuitous or related to PIL. Indeed, only a few lymphomas associated with PIL have been reported. Among 50 PIL patients reviewed, 3 had malignant lymphomas, that arose 3 to 25 years after the initial diagnosis . The interval from PIL diagnosis to lymphoma diagnosis was even 39 and 40 years in a study . Some lymphomas were confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum), i.e. in PIL involved sites, while in other patients they were extra-intestinal (retroperitoneum, mediastinum, bone) [60-63]. In the well-described histological and immunological studies, only B-cell lymphomas (large cells, small cells, centroblastic, immunoblasts) were encountered . Chemotherapy achieved regression of the exsudative enteropathy in only two of those previous cases [62,63].
Lymphoma may be related to PIL as a consequence of several mechanisms: (1) long-standing protein-losing enteropathy may be resolved after treatment (chemotherapy and/or radiotherapy) [62-64]; (2) lymphoma may cause secondary intestinal lymphangiectasia, (3) lymphoma in PIL could be associated with an immune deficiency. Indeed, a primary deficiency of B cells and/or helper T cells has been proposed in PIL, in combination with a secondary immune deficiency resulting from the loss of immunoglobulins and lymphocytes [39,40]. But no clear evidence of depressed intestinal immunity was found in PIL patients compared to those with other primary immunodeficiencies and having gut infections, like giardiasis.
PIL patients were reported to have diffuse and multiple cutaneous warts in association with lymphoma [65,66]. Widespread viral warts may be associated with a primary immune deficiency in PIL or secondary to lymphoma.
Although PIL patients have moderate-to-severe hypogammaglobulinemia and lymphopenia, their risk of pyogenic bacterial infection is not significantly elevated and opportunistic infections are uncommon. Only one case of a severe infection with group G streptococcal empyema was reported  and another had cryptococcal meningitis .
It is an uncommon disorder characterized by the replacement of hematopoietic cells and adipocytes by amorphous extracellular material composed of acid mucopolysaccharides. The only reported case of a gelatinous transformation of the bone marrow in a PIL patient was attributed to the malnutrition resulting from malabsorption .Management including treatment
Low-fat diet associated with supplementary medium-chain triglycerides (MCT) is the cornerstone of PIL medical management . It is likely that the absence of fat in the diet prevents engorgement of the intestinal lymphatics with chyle, thereby preventing their rupture with its ensuing protein and T-cell loss. MCT are directly absorbed into the portal venous circulation and thus provide nutrient fat but avoid lacteal engorgement. After a few weeks, this treatment may lead to reversal of clinical and biochemical signs (albuminemia, immunoglobulin levels and lymphocyte counts) . In patients not responding to a low-fat diet, enteral nutritional therapy (elemental, semi-elemental and polymeric diets) may be required. In a few very severe cases, total parenteral nutrition is warranted . The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. Long-term PIL monitoring essentially concerns its predominant clinical manifestation (edema). Laboratory analyses (albuminemia, lymphocyte counts, immunoglobulin levels) are required when lower limb edema becomes more pronounced.
In the literature, other treatments have been proposed to treat PIL. They can be used after or in combination with a low-fat diet associated with MCT supplementation. Their efficacy is variable and insufficiently evaluated.
A few authors reported that PIL patients responded to tranexamic acid (1 g, 3 times a day) [73,74], but these responses were heterogeneous with only partial disease attenuation. It was hypothesized that increasing plasma fibrinolysis might enhance lymphatic permeability to plasma proteins. Under antiplasmin treatment, a lower percentage of T lymphocytes became normalized together with serum immunoglobulin values. In addition, the therapy resulted in the disappearance endoscopically observed duodenal lesions .
In 1998, Ballinger and Farthing reported the efficacy of octreotide in one PIL patient . To date, few publications have supported the contribution of octreotide in PIL. Octreotide (150–200 μg, twice a day or the slow-release formulation) might lead to clinical, biochemical (albuminemia) and histological improvement [76,77]. The mechanism of action of the somatostatin analog on the gastrointestinal tract remains unclear. It has been shown that octreotide induces short-lasting splanchnic vasoconstriction in healthy volunteers and cirrhotic patients, and inhibits the absorption of triglycerides . Furthermore, somatostatin inhibits thoracic lymph flow in dogs . Octreotide may be useful in PIL patients in combination with a low-fat diet.
Small bowel resection is useful in the rare cases in which intestinal lymphangiectasia is segmental and localized (duodenum) [80,81]. Recurrent and/or bulky pleural effusions may lead to unilateral or bilateral surgical pleurectomy or talc pleurodesis .
Steroids were prescribed to patients with intestinal lymphangiectasia secondary to inflammatory disease with variable efficacy  and also to systemic lupus erythematosus patients with protein-losing enteropathy 
Albumin infusion is a symptomatic treatment proposed in patients with important serous effusion or uncomfortable lower limb edema. Repeated albumin intravenous supplementation may be useful to reduce edema and improve albuminemia but its efficacy is transient resulting from persistent lymph leakage into the bowel lumen.
PIL is a chronic debilitating disorder requiring constraining long-term dietary control based on a low-fat regimen associated with supplementary MCT. Lower limb edema is usually the main clinical manifestation but lymphedema may be associated. Lower limb lymphedema had its own particularities, including infectious complications (e.g., cellulitis) and requires specific long-term management (low-stretch bandage, manual lymph drainage, skin care, elastic hosiery) . These two conditions deteriorate the quality of life (difficulty to put on shoes, unattractive aspect of leg). PIL outcome may be severe even life-threatening when malignant complications (lymphoma) or serous effusion(s) (pleural, pericardic) occur.
Synonyms and related keywords: primary intestinal lymphangiectasia, congenital intestinal lymphangiectasia, Milroy disease, protein-losing gastroenteropathies, hypoproteinemia, lymphocytopenia, hypogammaglobulinemia, anergy, impaired allograft rejection, diarrhea, peripheral edema
Author: Raoul Joubran, MD Chief, Fellow, Department of Internal Medicine, Division of Gastroenterology/Hepatology, University of Louisville School of Medicine
Background: Traditionally, protein-losing gastroenteropathies have been classified into 3 groups (depending on the mechanism of their etiology), which include (1) those causing mucosal damage leading to increased permeability to protein (usually not involving mucosal ulcerations), (2) those with mucosal erosions and/or ulcerations, and (3) those in which protein loss is secondary to mechanical lymphatic obstruction. While a more detailed discussion on Protein-Losing Enteropathy
Pathophysiology: Intestinal lymphangiectasia is a disease characterized by hypoproteinemia and lymphocytopenia, resulting from blocked intestinal lymphatics and loss of lymph fluid into the gastrointestinal (GI) tract. This leads to immunologic abnormalities, including hypogammaglobulinemia, anergy, and impaired allograft rejection. In addition to the loss of other serum components (eg, lipids), iron and certain trace metals may also be affected.
** For complete article - see link below**
Hypoproteinemia in intestinal
lymphangiectasia; Contribution of albumin
"trapping" in the lymphedematous extremity
T Herskovic, SJ Winawer, R Goldsmith, R Klein and N Zamcheck
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
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Pub Med Related Links Page - Waldmann's Disease
ICD10 and ICD-9 Codes
ICD-9 Broadly Classified as:
2008 ICD-9-CM Volume 1 Diagnosis Codes
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Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.
Disorders Support Group @ Yahoo Groups
While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.
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