2 - World Journal of Gastroenterology
2 - World Journal of Gastroenterology
2 - World Journal of Gastroenterology
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may result. The mechanisms involved for malabsorption<br />
<strong>of</strong> fat and fat soluble vitamins are not fully defined and<br />
need to be further explored. However, osteomalacia associated<br />
with vitamin D deficiency has been noted [20] and<br />
tetany attributed to hypocalcemia has been reported [21] .<br />
Rarely, yellow nails have been described (i.e. “yellow<br />
nail syndrome”) in primary intestinal lymphangiectasia<br />
with dystrophic ridging and loss <strong>of</strong> the nail lunula. In addition,<br />
lymphedema and pleural effusions were noted [22] .<br />
Finally, an intriguing association with autoimmune polyglandular<br />
disease type 1 has been described [23,24] .<br />
DIAGNOSIS<br />
Diagnosis is defined by endoscopic evaluation and biopsy<br />
<strong>of</strong> duodenum and/or jejunum [1, 2] or alternatively from<br />
surgically resected small intestine. Dilated lacteals are detected<br />
in the mucosa, sometimes extending into the submucosa<br />
(Figures 1 and 2). Usually, the overlying small intestinal<br />
epithelium is completely normal. Sometimes, ileal<br />
biopsies from ileocolonoscopy may show the small intestinal<br />
histopathological changes. High-resolution magnifying<br />
video endoscopy may have an important role in detection<br />
<strong>of</strong> intestinal lymphangiectasia [25] . Video capsule studies<br />
may permit evaluation <strong>of</strong> the extent <strong>of</strong> the lymphangiectasia<br />
including the “yellow nail syndrome” and has<br />
been confirmed with surgical exploration [27-29] . Doubleballoon<br />
enteroscopy has also emerged in the evaluation<br />
<strong>of</strong> malabsorption and up to 13% <strong>of</strong> patients were found<br />
to have yellow and white submucosal plaques, likely to be<br />
lymphangiectasis [30,31] . Although radiotracers and direct<br />
lymphatic imaging were <strong>of</strong>ten historically used, magnetic<br />
resonance imaging has also been applied in patients with<br />
intestinal lymphangiectasia to evaluate intestinal, mesenteric<br />
and thoracic duct changes [32] .<br />
Associated immunological changes have been described<br />
in a number <strong>of</strong> studies [33-36] . These findings include<br />
hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia.<br />
Lymphocytopenia occurs with B-cell depletion<br />
reflected by diminished immunoglobulins IgG, IgA and<br />
IgM, as well as T-cell depletion, especially in the number<br />
<strong>of</strong> CD4+ T-cells as naïve CD45RA+ lymphocytes. In addition,<br />
functional changes occur including impaired antibody<br />
responses and prolonged skin allograft rejection may<br />
result. Finally, a recent report indicates that T-cell thymic<br />
production failed to compensate for enteric T-lymphocyte<br />
loss suggesting multiple mechanisms are involved in lymphopenia<br />
associated with lymphangiectasia [37] .<br />
Enteric protein loss may be suspected if fecal alpha-<br />
1-antitrypsin is increased. Radio-labeled albumin studies<br />
may demonstrate increased loss but prolonged scanning<br />
may be required as protein loss may be periodic or intermittent.<br />
In some cases, localization <strong>of</strong> the site <strong>of</strong> protein<br />
loss may also be possible [38] . Imaging with ultrasound<br />
or computerized tomography may define intestinal wall<br />
thickening, mesenteric “edema” or ascites [39-41] . Magnetic<br />
resonance imaging has also been reported for use in the<br />
diagnosis <strong>of</strong> protein losing enteropathy [42] . Lymphoscintigraphy<br />
may also be used to anatomically define the<br />
lymphatic system but this procedure has largely become<br />
historical, less <strong>of</strong>ten performed and may correlate poorly<br />
with the severity <strong>of</strong> protein loss [43] .<br />
It is especially critical to ensure that changes <strong>of</strong> intestinal<br />
lymphangiectasia are not secondary to some other<br />
cause, particularly from a “downstream” obstruction,<br />
including another intestinal disease (e.g. Crohn’s disease,<br />
Whipple’s disease from Tropheryma whipplei infection [44] , intestinal<br />
tuberculosis), radiation- and/or chemotherapy-induced<br />
retroperitoneal fibrosis, or even a circulatory cause<br />
(e.g. constrictive pericarditis). Many gastric disorders (e.g.<br />
Mentrier’s disease) or inflammatory disorders involving the<br />
intestine (e.g. protein losing enteropathy in systemic lupus<br />
erythematosus) may also cause protein loss without intestinal<br />
lymphangiectasia [45] . Finally and particularly significant<br />
are malignant lymphomas that may secondarily cause<br />
lymphatic obstruction and intestinal lymphangiectasia with<br />
intestinal protein loss. In these, resolution <strong>of</strong> the proteinlosing<br />
enteropathy with the intestinal lymphangiectasia<br />
may result from lymphoma treatment [46-48] . Conversely, it<br />
also conceivable that lymphoma may complicate the clinical<br />
course <strong>of</strong> long-standing intestinal lymphangiectasia<br />
per se. Both intestinal and extra-intestinal lymphomas have<br />
been described, usually B-cell type, during the course <strong>of</strong><br />
long-standing intestinal lymphangiectasia [49] . A definite<br />
mechanism has not been defined although depressed immune<br />
surveillance may result from ongoing and persistent<br />
depletion <strong>of</strong> immunoglobulins and lymphocytes.<br />
THERAPY<br />
Freeman HJ et al . Intestinal lymphangiectasia<br />
Treatment has traditionally included a low fat diet along<br />
with a medium-chain triglyceride oral supplement [50] .<br />
The latter directly enters the portal venous system and<br />
bypasses the intestinal lacteal system. Some believe that<br />
reduced dietary fat prevents lacteal dilation and possible<br />
rupture with loss <strong>of</strong> protein and lymphocyte depletion.<br />
In some, this therapy can cause reversal <strong>of</strong> clinical and<br />
biochemical changes, being more effective in children<br />
than adults [51] . In some that fail to respond, other forms<br />
<strong>of</strong> nutritional support have been required [52] .<br />
Other therapies have been reported. Tranexamic acid,<br />
an antiplasmin, has been used to normalize immunoglobulin<br />
and lymphocyte numbers [53] . Octreotide was reported<br />
to be useful but the mechanism is not clear [54] . Segmental<br />
small bowel resection for localized areas <strong>of</strong> lymphangiectasia<br />
has been recorded [55] . Steroids remain controversial<br />
although effectiveness in systemic lupus erythematosus<br />
with protein-losing enteropathy has been recorded. Infusions<br />
<strong>of</strong> intravenous albumin may provide temporary<br />
effectiveness but usually this exogenous source is also<br />
metabolized or lost. Management <strong>of</strong> lower limb edema is<br />
also important, usually with elastic bandages or stockings.<br />
The long-term natural history <strong>of</strong> intestinal lymphangiectasia<br />
has been evaluated only to a limited extent. In a<br />
recent report [56] , dietary intervention appeared to be effective<br />
in most cases, particularly in pediatric-onset disease.<br />
In the same report, 5% appeared to develop malignant<br />
WJGO|www.wjgnet.com 21<br />
February 15, 2011|Volume 3|Issue 2|