Information on all the types of lymphangiectasia, including intestinal, pulmonary, renal, cutaneous (skin). Sponsored by Pat O'Connor

Saturday, September 30, 2006

Medium Chain Triglycerides (MCT) and Intestinal Lymphangiectasia

Medium Chain Triglycerides (MCT) and Intestinal Lymphangiectasia

One methods used in helping to manage intestinal lymphangiectasia is to follow a specialized diet involving what is called medium chain triglycerides.

Here is some helpful information on MCT's, what they are and what they do.

Medium Chain Triglycerides

What do they do?

Medium-chain triglycerides (MCT) are a class of fatty acids. Their chemical composition is of a shorter length than the long-chain fatty acids present in most other fats and oils, which accounts for their name. They are also different from other fats in that they have a slightly lower calorie content1 and they are more rapidly absorbed and burned as energy, resembling carbohydrate more than fat.2

MCT have been shown to increase calorie burning compared with other fats.3 4 However, researchers estimate that half of the calories in the diet would have to be eaten as MCT for significant weight loss to occur.5 Obese women on a calorie-restricted diet using MCT for 24% of total calories, experienced no greater weight loss after three months, than when regular fat was used.6 Whether MCT would help people lose weight on a normal diet has not been adequately studied.

Since MCT is more rapidly used for energy than other fats, some athletes have been interested in its use, especially during prolonged endurance exercise.7 However, no effect on carbohydrate sparing or endurance exercise performance has been shown, with moderate amounts of MCT (30–45 grams).8 9 Trials using very large amounts (about 85 grams) have produced conflicting results. One study found increased performance when MCT was added to a 10% carbohydrate solution,10 and another study actually reported decreased performance, probably due to gastrointestinal distress, in athletes using MCT.11

Because some short-term studies have shown that MCT lowers blood glucose levels, a group of researchers investigated the use of MCT to treat people with type 2 (adult onset or non-insulin-dependent) diabetes mellitus.12 In nonhospitalized people with diabetes who consumed MCT for an average of 17.5% of their total calorie intake for 30 days, MCT did not improve diabetic control by most measures.13

Where are they found?

Medium chain triglycerides are found in coconut oil, palm kernel oil, and butter. MCT are also available as a supplement.

Who is likely to be deficient?

Most people consume adequate amounts of fat in their diets and many people consume excessive amounts, so extra fat intake as medium chain triglycerides is unnecessary.

How much is usually taken?

The best amount of medium chain triglycerides to take is currently unknown. Athletes are not likely to benefit from less than 50 grams during exercise. Larger amounts may possibly help some, but may also impair performance if not combined with carbohydrate.

Are there any side effects or interactions?

Consuming medium chain triglycerides on an empty stomach can lead to gastrointestinal upset. Anyone with cirrhosis or other liver problems should check with a doctor before using MCT. Two reports suggest that MCT may raise serum cholesterol and/or triglycerides.14 15 MCT is actually the preferred fatty acid source for cirrhotic patients, but only when used intermittently.16 At the time of writing, there were no well-known drug interactions with medium chain triglycerides.


1. Bach AC, Ingenbleek Y, Frey A. The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy? J Lipid Res 1996;37:708–26. 2. Bach AC, Babayan VK. Medium-chain triglycerides—an update. Am J Clin Nutr 1982;36:950–62. 3. Scalfi L, Coltorti A, Contaldo F. Postprandial thermogenesis in lean and obese subjects after meals supplemented with medium-chain and long-chain triglycerides. Am J Clin Nutr 1991;53:1130–3. 4. Seaton TB, Welle SL, Warenko MK, et al. Thermic effect of medium-chain and long-chain triglycerides in man. Am J Clin Nutr 1986;44:630–4. 5. Bach AC, Ingenbleek Y, Frey A. The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy? J Lipid Res 1996;37:708–26. 6. Yost TJ, Eckel RH. Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution. Am J Clin Nutr 1989;49:326–30. 7. Jeukendrup AE, Saris WH, Schrauwen P, et al. Metabolic availability of medium-chain triglycerides coingested with carbohydrates during prolonged exercise. J Appl Physiol 1995;79:756–62. 8. Jeukendrup AE, Wagenmakers AJM, Brouns F, et al. Effects of carbohydrate (CHO) and fat supplementation on CHO metabolism during prolonged exercise. Metabolism 1996;45:915–21. 9. Satabin P, Portero P, Defer G, et al. Metabolic and hormonal responses to lipid and carbohydrate diets during exercise in man. Med Sci Sports Exer 1987;19:218–23. 10. van Zyl CG, Lambert EV, Hawley JA, et al. Effects of medium-chain triglyceride ingestion on carbohydrate metabolism and cycling performance. J Appl Physiol 1996;80:2217–25. 11. Jeukendrup AE, Thielen JJHC, Wagenmakers AJM, et al. Effect of medium-chain triacylglycerol and carbohydrate ingestion during exercise on substrate utilization and subsequent cycling performance. Am J Clin Nutr 1998;67:397–404. 12. Eckel RH, Hanson AS, Chen AY, et al. Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in non-insulin dependent diabetics. Diabetes 1992;41:641–7. 13. Trudy J, Yost RN, Erskine JM, et al. Dietary substitution of medium-chain triglycerides in subjects with non-insulin dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism. J Am Coll Nutr 1994;13:615–22. 14. Cater NB, Heller HJ, Denke MA. Comparison of the effects of medium-chain triacylglycerols, palm oil, and high oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and lipoprotein concentrations in humans. Am J Clin Nutr 1997;65:41–5. 15. Hill JO, Peters JC, Swift LL, et al. Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. J Lipid Res 1990;31:407–16. 16. Fan ST. Review: nutritional support for patients with cirrhosis. J Gastroenterol Hepatol 1997;12:282–6. Mednd


Medium-chain triglycerides (MCT)


Medium-chain triglycerides (MCTs) are a special class of fatty acids. Normal fats and oils contain long-chain fatty acids (LCTs). Compared to these fatty acids, MCTs are much shorter in length. Therefore, they resemble carbohydrates more than fat. As a result, they are more easily absorbed, digested, and utilized as energy than LCTs.

Medium-chain triglycerides are found naturally in milk fat, palm oil, and coconut oil. Commercial MCT oil, available as liquid and capsules, is obtained through lipid fractionation, the process in which MCTs are separated from other components of coconut oil. Medium-chain triglycerides were originally formulated in the 1950s as an alternative food source for patients who are too ill to properly digest normal fats and oils.

The long chains of LCTs require a lot of bile acids and many digestive steps to be broken down into smaller units that can be absorbed into the bloodstream. Once in the bloodstream, they are absorbed by fat cells and stored as body fat. In contrast, the medium-chain triglycerides are more water-soluble and are able to enter the bloodstream quicker because of their shorter lengths. Once in the bloodstream, they are transported directly into the liver. Thus, MCTs are an immediately available source of energy and only a tiny percent is converted into body fat.

Medium-chain triglycerides were first used in the mid-1900s to reduce seizures with the help of the ketogenic diet. In the 1980s, MCTs became popular in sports as a substitute for normal dietary fats or oils. They quickly became a favorite energy source for many athletes, such as marathon runners, who participate in endurance sports. These athletes require a quick source of energy, which is readily supplied by carbohydrates. However, diets high in carbohydrates may cause rapid increase in insulin production, resulting in substantial weight gain, diabetes, and other health problems. Dietary fats or oils are not a readily available source of energy. In addition, they are believed to make the body fatter. MCT is also a form of fat; therefore, it is high in calories. Yet, unlike normal fats and oils, MCTs do not cause weight gain because they stimulate thermogenesis (the process in which the body generates energy, or heat, by increasing its normal metabolic, fat-burning rate). A thermogenic diet, which is high in medium-chain triglycerides, has been proposed as a type of weight loss regime.

General use

Endurance sport nutrition

Medium-chain triglycerides are often used by athletes to increase their endurance during sports or exercise regimes. MCTs are an immediate source of energy, and as such, the body can use them as an alternative energy source for muscle during endurance exercise. However, if consumed in moderate amounts (30 to 45 grams), MCTs are not very effective in either decreasing carbohydrate needs or in enhancing exercise endurance. Increased consumption may help.

One study evaluated six athletes at different points during a 25-mile cycling trial.

They were given either a medium-chain triglyceride beverage, a carbohydrate drink, or a combined MCT-carbo-hydrate mixture. The fastest speed was achieved when the athletes used the MCT-carbohydrate blend. The worst performance was associated with sport drinks containing MCT alone (without carbohydrate). Therefore, to gain significant increases in endurance, it is generally recommended that an athlete consume at least 50 grams of MCTs per day in combination with some carbohydrates. However, dosages exceeding 30 grams often cause gastrointestinal upset, which can diminish an athlete's performance.

MCT products available in the market may have high water content or contain unwanted ingredients. Therefore, athletes should buy MCT-only products, and mix a small amount into carbohydrate soft drinks. Alternatively, they can purchase premixed MCT sport drinks, such as a brand known as SUCCEED.

Thermogenic diet

MCTs are popular among body builders because they help reduce carbohydrate intake, while allowing them ready access to energy whenever they need it. MCTs also have muscle-sparing effects. As a result, they can build muscles while reducing fats. However, this does not mean that these athletes will become healthier, because an improvement in body physique does not always correlate with higher fitness levels.

Pre-competition diet

Compared to carbohydrates, medium-chain triglycerides are a better and more efficient source of quick energy. They help conserve lean body mass because they prevent muscle proteins from being used as energy. Therefore, some athletes load up on medium-chain triglycerides the night before a competition. However, MCT intake should be raised gradually to allow the body to adapt to increasing MCT consumption.

If MCT consumption abruptly increases, incomplete MCT metabolism may occur, producing lactic acid in the body and a rapid rise of ketones in the blood, which can make the person ill.

Weight-loss diet

Studies have shown that MCT may increase metabolism, which is the rate that the body burns fat. It is believed that sustained increases in metabolic rate cause the body to burn more fat, resulting in weight loss. However, for any kind of meaningful weight loss, a person would have to consume more than 50% of total daily caloric intake in the form of medium-chain triglycerides.

Treatment of seizures

A ketogenic diet, or diet containing mostly medium-chain triglycerides, offers hope for those who have seizures that cannot be controlled by currently available drugs. Excessive consumption of MCTs produces ketones in the body; therefore, this type of diet is called a ketogenic diet. It has proven effective for some epileptic patients.

Nutritional supplements

MCTs are the preferred forms of fat for many patients with fat malabsorption problems.

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Many diseases cause poor fat absorption. For instance, patients with pancreatic insufficiency do not have enough pancreatic enzymes to break down LCTs. In children with cystic fibrosis, thick mucus blocks the enzymes that assist in digestion. Another fat absorption condition is short-bowel syndrome, in which parts of the bowel have been removed due to disease. Stressed or critically ill patients also have a decreased ability to digest LCTs. Unlike LCTs, medium-chain triglycerides are easily absorbed by patients with malabsorption conditions. These patients benefit most from oral preparations that contain MCTs as the primary source of fat (up to 85% of fat caloric intake). Several scientific studies have shown MCT to be effective in treating fat malabsorbtion, chronic diarrhea, and weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS).

Many MCT products can be found in local health food stores or ordered through pharmacies. Before purchasing these products, patients should consult their doctors or registered dietitians for advice concerning appropriate dosage and use. MCT oil is not used for cooking. However, it can be used for tube feeding in critically ill patients. Healthy people may take it orally, by itself or mixed with water, juice, ice cream, or pudding.


Available medium-chain triglyceride products include:

·MCT oil ·sports drinks
·energy bars
·meal replacement beverages


·People with hepatic encephalopathy, brain and nervous system damage that occurs as a complication of liver disorders, should not take MCT.
·High consumption of medium-chain triglycerides can cause abdominal pain, cramps, and diarrhea.
·Long-term high-level MCT consumption is associated with increased risk of heart disease and other conditions. Even moderate consumption of medium-chain triglycerides can increase cholesterol and triglyceride levels. Therefore, no more than 10% of a person's diet should come from MCTs.
·Diabetic athletes and those with liver disease should not use MCT products.
·MCT oil should not completely replace all dietary fats, as this would result in a deficiency of other fatty acids- essential fatty acids- that the human body needs from food sources. To avoid essential fatty acid deficiencies, a person should also include omega-3 and omega-6 fatty acids in their diets. Good sources of omega-3 include fish, fish oils, or flaxseed oil. Omega-6 fatty acids are often found in vegetable oils and evening primrose oil. The omega-3 fats have several additional health benefits, such as alleviating inflammation and protecting the body against heart disease.
·A person should not take medium-chain triglyceride products on an empty stomach, as this may cause gastric upset.
·MCT oil is not for cooking. It is usually consumed in its uncooked form as sport bars, or mixed with a carbohydrate drink, protein shake, or other products.
·MCT oil leaches into plastic bags and containers. Therefore, non-plastic containers should be used for MCT oil storage.

Side effects

There are a few adverse effects associated with MCT use. Eating foods containing medium-chain triglycerides on an empty stomach often causes gastrointestinal upset. Regular consumption of MCTs may increase cholesterol and triglyceride blood levels.


There have been no reported interactions between MCTs and other drugs. Resources


Antonio, Jose, and Jeffery Stout. Supplements for Endurance Athletes. Champaign, IL: Human Kinetics, 2002. Ivy, John, and Robert Portman. The Performance Zone: Your Nutrition Action Plan for Greater Endurance and Sports Performance (Teen Health Series). North Bergen, NJ: Basic Health Publications, Inc., 2004. Ryan, Monique. Sports Nutrition for Endurance Athletes. Boulder, CO: Velo Press, 2002. Stapstrom, Carl E. Epilepsy and the Ketogenic Diet: Clinical Implementation & the Scientific Basis. Totowa, NJ: Humana Press, 2004.


(No author). "Medium-Chain Triglycerides May Help Promote Weight Loss." Obesity, Fitness & Wellness Week (March 29, 2003): 5. (No author). "Medium Chain Triglycerides." Alternative Medicine Review (October 2002): 418-20. Donnell, S.C., et al. "The Metabolic Response to Intravenous Medium-Chain Triglycerides in Infants After Surgery." Alternative Medicine Review (February 2003): 94. St-Onge, M.P., and P.J. Jones. "Physiological Effects of Medium-Chain Triglycerides: Potential Agents in the Prevention of Obesity." Alternative Medicine Review (June 2002): 260. St-Onge, M.P., et al. "Medium-Chain Triglycerides Increase Energy Expenditure and Decrease Adiposity in Overweight Men." Obesity Research (March 2003): 395-402.


American Dietetic Association (ADA) Consumer Information Hotline. (800)366-1655..


Klein, Samuel. "Lipid Metabolism During Exercise." Health-World Online. Abstract from NIH Workshop: The Role of Dietary Supplements for Physically Active People. article. "Medium-Chain Triglycerides." . Healthline


Super page with low-fat and MCT recipes ht

Little Leakers website


MCT Cookbook


Medium-Chain Triglycerides

Friday, September 22, 2006

Octreotide Treatment and Intestinal Lymphangiectasia

Octreotide in intestinal lymphangiectasia: lack of a clinical response and failure to alter lymphatic function in a guinea pig model.

Makhija S, von der Weid PY, Meddings J, Urbanski SJ, Beck PL. Department of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada.

Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing lymphatic pumping.

PMID: 15565209 [

A 47-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to our hospital with diarrhea and generalized edema and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia by intestinal biopsy and 99mTc albumin scan. During hospitalization, he received subcutaneous octreotide therapy. After 2 weeks of octreotide therapy, follow-up albumin scan showed no albumin leakage, and the serum albumin level was sustained. We speculate that liver cirrhosis can be a cause of intestinal lymphangiectasia and administration of octreotide should be considered for patients with intestinal lymphangiectasia whose clinical and biochemical abnormalities do not respond to a low-fat diet. 2004 Jun; 19 (3): 466- 469 Journal of Korean Medical Science

PubMed - indexed for MEDLINE]



S Makhija, P-Y von der Weid, J Meddings, PL Beck GI and Mucosal Inflammation Research Groups, University of Calgary, Calgary, Alberta

We present two patients with intestinal lymphangiectasia. Intestinal lymphangiectasia is rare cause of protein losing enteropathy. Management is often ineffective and generally includes a low fat diet and medium chain triglyceride (MCT) oil. Several medications have also been tried without success. Recently octreotide has been used in a small number of patients with mixed results. It is unclear why octreotide was used in these cases for there have been no studies to date assessing the actions of this agent on lymphatic function.


Assess the role of octreotide on lymphatic function.


To investigate whether octreotide directly affects lymphatic pumping function, we assessed its effect on lymphatic vessels of the ileal portion of the guinea-pigs mesentery. This intra-vital preparation is a well-established model that has been used to characterize physiological and pharmacological properties of lymphatic pumping. The contractile activity of lymphatic vessels was monitored via video microscopy and vessel diameter was analyzed in real time using a video-dimension analyzer. A 5 min control period of contractile activity was recorded before octreotide (Sandostatin, Novartis, Basle, CH) was applied for 4 min, at various concentrations.


Octreotide had no effect on lymphatic vessel pumping activity over a wide range of concentrations (20 nM to 10 µM). Despite the absence of response to octreotide, the same vessels responded to treatments with 5-HT with a decrease in constriction frequency (47.3±10.5% of control) and to application of histamine with an increase in pumping (125.3±20.9% of control). Thus, although pumping of guinea-pig mesenteric lymphatic vessels could be altered by known modulatory agents, it was not affected by octreotide. Of our two clinical cases, one patient was managed with MCT oil with a good response while the second patient failed MCT oil therapy and was then tried empirically on octreotide without clinical response.


In a bedside-to-bench approach we could not find any evidence that octreotide enhanced lymphatic function in our animal model nor did the one patient that empirically received octreotide respond to this intervention.



See Also:

All About Lymphangiectasia 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.

To Subscribe:

Primary Intestinal Lymphangiectasia - Treatments

Primary Intestinal Lymphangiectasia

Charles M. Bliss, MD and Paul C. Schroy III, MD, MPH

Current Treatment Options in Gastroenterology 2004, 7:3-6

Current Science, Inc. ISSN 1092-8472 2006 Current Science, Inc.

Opinion Statement

A high-protein, low-fat diet supplemented with medium chain triglycerides (MCT) is the simplest, most effective, and most widely prescribed treatment with the fewest side effects. Octreotide has been helpful in cases in which treatment with MCT has failed, but it is costly and requires parenteral administration. Antiplasmin therapy may have some role when evidence of increased fibrinolysis is present. Surgery is reserved for palliation of large ascites or resection of isolated lesions.


Primary intestinal lymphangiectasia (PIL) is a congenital disorder of the lymphatic system characterized by dilated and tortuous intestinal lymphatics resulting from impaired lymphatic drainage. This condition can occur in any area of the body; in the intestine, the impaired lymphatic drainage leads to leakage of protein-rich chyle into the intestinal lumen, causing protein-losing enteropathy, hypoalbuminemia, and peripheral or mucosal edema. Mucosal edema can, in turn, lead to malabsorption and steatorrhea. Extraintestinal lymphatics can also be involved, resulting in peripheral edema, chylous ascites, pleural effusions, and pericardial effusions. Lymphopenia is also common and indicates failure of lymphocytes in the lymphatics to return to the general circulation, presumably due to the structural changes of the lymphatics. Diagnosis is usually made by radiographic studies, which show edema of the small bowel, or by endoscopy and small bowel biopsy, which reveal the characteristic dilated lacteals of the mucosa.

Secondary intestinal lymphangiectasia is a similar syndrome clinically, but is caused by other disorders that damage or obstruct intestinal lymphatics. These disorders include malignancy, infection, and inflammatory bowel disease. Treatment of these cases is directed at the underlying cause of the lymphatic damage and is beyond the scope of this review [1, 2, 3].

Because of the rarity of PIL, there are no long-term randomized, controlled studies to guide treatment. Experience in treating PIL has been derived mostly from case reports and small case series. Several approaches have been tried; however, because PIL represents a spectrum of disease severity and etiology sharing a common phenotype, the results of any one treatment are variable. One of the simplest and most widely used treatments is dietary modification, with replacement of fat with medium chain triglycerides (MCT). Because MCTs are absorbed rapidly by the intestinal mucosa and can be metabolized and excreted directly into the portal venous system rather than via intestinal lacteals, there is a reduced load on the damaged lymphatic system. As long as dietary compliance is maintained, patients on an MCT diet have achieved symptom relief for many years. Noncompliance may lead to recrudescence of symptoms [1, 2, 3].

Response to treatment with antiplasmin or tranexamic acid has been reported in cases of PIL associated with increased fibrinolysis. It has been postulated that in these cases, increased lymphatic pressure can rupture lymphatic-venous anastomoses, leading to bleeding in addition to the other manifestations of PIL. Treatment has been shown to reduce bleeding but has no effect on lymphocyte counts, suggesting that the underlying lymphatic disorder is unaffected. [4**, 5].

Treatment with octreotide has also been helpful in select cases of PIL. It is felt that octreotide reduces the secretion of bile into, and chyle from, the intestine by binding to somatostatin receptors in the intestinal lymphatics and intestinal vasculature. Decrease in bile flow leads to diminution of fat emulsification in the intestinal lumen, and thus decreases the absorption of dietary triglycerides into the already overloaded lacteals. Octreotide may also reduce protein losses by decreasing intestinal motility and secretion. As with antiplasmin therapy, however, octreotide fails to induce an increase in lymphocyte counts, again suggesting that the underlying lymphatic disorder is unaffected [6, 7*, 8*].

Finally, in selected cases, surgery to remove isolated segments of involved small bowel has been attempted. Most cases of PIL present with diffuse small bowel involvement, which is not amenable to treatment by resection. However, in cases where a localized area of severe abnormality exists, resection may be helpful [9, 10, 11*]. Surgery can also be performed to palliate chylous ascites, pericardial effusions, and pleural effusions unresponsive to other treatments. Surgical options include creation of pericardial or pleural windows, or placement of artificial shunts, such as a peritoneovenous shunt. Peritoneovenous shunts may be prone to infection and thrombosis and have been associated with disseminated intravascular coagulation [9, 12].


Diet and Lifestyle

A high-protein, low-fat diet is essential to recoup gastrointestinal protein losses and minimize steatorrhea. Addition of MCTs allows more caloric intake and compliance with dietary restrictions. Adherence to this diet, supplemented with MCTs, has been shown to improve symptoms of PIL (eg, diarrhea and steatorrhea) and spur growth. However, this approach fails to increase serum protein levels or lymphocyte counts, suggesting little effect on the underlying disease process. Furthermore, noncompliance with the diet can lead to relapse.

Medium chain triglycerides

Standard dosage: 15 cm3 orally three times daily. It may be mixed with other foods.

Contraindications: Hepatic encephalopathy.

Main drug interactions: None known.

Main side effects: Nausea, vomiting, diarrhea.

Special points Use: caution in patients with cirrhosis or steatosis. Monitor for deficiency of essential fatty acids.

Cost effectiveness: The average wholesale price of a 1-quart bottle (which lasts for 21 days) is $49.00.

Pharmacologic treatment

The aims of octreotide therapy in PIL are to decrease hepatic secretion of bile, intestinal secretion, and slow intestinal transit.

• The aim of tranexamic acid therapy is to reduce local fibrinolysis, leading to reduction in mucosal bleeding and lymph losses.

Octreotide Octreotide is a synthetic analogue of somatostatin, which has been successful in some cases not responding to other treatments [6, 7*, 8*].

Standard dosage: 100 mg2 two or three times daily.

Contraindications: History of hypersensitivity.

Main drug interactions: Diuretics, b-blockers, calcium blockers, insulin, and hypoglycemics.

Main side effects: Bradycardia, arrhythmia, abdominal pain, nausea, vomiting, hyperglycemia, hypoglycemia, flu-like symptoms.

Special points: Use caution in patients with diabetes, cardiac disease, liver disease, and renal disease.

Cost effectiveness: The average wholesale price of 20 vials of 100 mg/1 mL of octreotide (which last for 7 to 10 days) is $371.42.

Tranexamic acid

Although effective in isolated cases, other case reports show no beneficial effect for tranexamic acid [4**, 5, 13, 14].

Standard dosage: 1000 mg orally three times daily.

Contraindications: Disseminated intravascular coagulation, subarachnoid hemorrhage, acquired defect in color vision, hypersensitivity.

Main drug interactions: Chlorpromazine (increases vasospasm), anti-inhibitor coagulation complex (increased thrombosis).

Main side effects: Nausea, vomiting, diarrhea, thromboembolism, rash, seizure.

Special points: More likely to be effective if evidence of increased fibrinolysis. Use caution in patients with renal disease because tranexamic acid is excreted renally.

Cost effectiveness: The average wholesale price of 100 500-mg tablets is $315.00. (A 30-day supply at the recommended dosage would be 180 tablets.)


• The aim of surgical treatment in PIL is palliation of severe disease. Small bowel resection

Standard procedure:

Small bowel resection.


Poor performance status of patient.

Complications: Infection, bleeding, anastomotic leak.

Special points: Effective only in cases with a localized area of bowel involved.

Cost effectiveness: Cost of hospital stay, surgery, and follow-up.

Peritoneovenous shunt placement

Standard procedure:

Peritoneovenous shunt placement.

Contraindications: Poor performance status of patient.

Complications: Infection, bleeding, thrombosis of shunt, disseminated intravascular coagulation.

Special points: Used for palliation of massive chylous ascites.

Cost effectiveness: Cost of procedure, hospitalization, recovery, and follow-up.

References and Recommended Reading

Recently published papers of particular interest have been highlighted as: * Of importance ** Of major importance

1. Salomons HA: Endoscopic features of long-standing primary intestinal lymphangiectasia. Gastrointest Endosc 1995, 41:516-518. 2. Tift WL: Intestinal lymphangiectasia: long-term results with MCT diet. Arch Dis Child 1975, 50:269-276. 3. Vardy PA: Intestinal lymphangiectasia: a reappraisal. Pediatrics 1975, 55:842-851. 4. ** MacLean JE: Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy. Pediatrics 2002, 109:1177-1180. This study is a current case report with review of the literature, including description of effective treatment with tranexamic acid when MCT and octreotide had failed. Also included in the discussion are the other treatment options, which are MCT and octreotide. 5. Mine K, et al.: Intestinal lymphangiectasia markedly improved with antiplasmin therapy. Gastroenterology 1989, 96:1596-1599. 6. Bac DJ, et al.: Octreotide for protein-losing enteropathy with intestinal lymphangiectasia. Lancet 1995, 345:1639. 7. * Heikenen JB, et al.: Octreotide in pediatric patients. J Pediatr Gastroenterol Nutr 2002, 35:600-609. A review of the uses of octreotide in many diseases in children, including PIL. 8. * Jackson R: Intestinal lymphangiectasia and octreotide. J Pediatr Gastroenterol Nutr 2001, 33:408-409. A recent report of two cases that responded to octreotide after MCT therapy had failed. 9. Muzaffar K: Primary intestinal lymphangiectasia: surgical implications. Am Surg 1972, 38:288-291. 10. Persic M: Intestinal lymphangiectasia and protein-losing enteropathy responding to small bowel resection. Arch Dis Child 1998, 78:194. 11. * Uguralp S, et al.: Primary intestinal lymphangiectasia: a rare disease in the differential diagnosis of acute abdomen. J Pediatr Gastroenterol Nutr 2001, 33:508-510. A case of PIL presenting with involvement of a local segment of small intestine that was successfully treated with resection. 12. White SM: Operative ascitic drainage in a patient with primary intestinal lymphangiectasia. Anaesthesia 2003, 58:396-397. 13. Heresbach D, et al.: Intestinal lymphangiectasia: lack of efficacy of antiplasmin therapy? Gastroenterology 1991, 100:1152-1153. 14. Mine K: Intestinal lymphangiectasia: lack of efficacy of antiplasmin therapy? [comment]. Gastroenterology 1991, 101:1761. Current Treatment Options in Gastroenterology 2004,


See Also: All About Lymphangiectasia 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.

To Subscribe:

Sunday, September 17, 2006

Acquired lymphangiectasis after breast conservation treatment for breast cancer

Acquired lymphangiectasis after breast conservation treatment for breast cancer: Report of a case

Ismet Tasdelen1, Sehsuvar Gokgoz1, Ela Paksoy1, Omer Yerci2, Sibel Kahraman

Cetintas3, Mutlu Demiray4, Veysi Samsa1Dermatology Online Journal 10 (1): 9

From the Departments of Surgery1, Pathology2, Radiation Oncology3, and Medical Oncology4, School of Medicine, University of Uludag, 16059, Bursa, Turkey.


Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histological features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculobullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe patient who had these lesions after treatment for cancer. Although a number of treatment options are available, we have found cryosurgery and electrocautery to be particularly effective.


Acquired lymphangiectasis (AL) represent superficial lymphatic dilatation caused by a wide range of scarring processes and occurs as a consequence of lymphatic damage by an external cause, leading to obstruction of local lymphatic drainage. It has been reported after treatment of breast, vulva, cervix, skin, and lung cancers and it is sometimes termed acquired lymphangiomas [1]. This condition has also been associated with metastatic lymph node invasion and obstruction, scleroderma, and scrofuloderma. Acquired lymphangiomas most commonly occur in adults as a late sequel of mastectomy and radiation therapy. Patients usually present with numerous translucent vesicles in a chronic lymphedematous area several years after surgery with or without radiation therapy [2]. This report describes a case of acquired lymphangiectasis of the breast in 68-year-old woman. We discuss the clinical features, diagnosis, and treatment of acquired lymphangiectasis of the breast with a literature review.

Clinical summary
A 68-year-old woman presented to our outpatient clinic for evaluation of multiple small vesicular lesions on the left breast. Three years earlier, she had had a breast conservative treatment—lumpectomy, chemotherapy, and radiation therapy for grade II invasive lobular carcinoma of the left breast. The breast lesions started to develop three years after breast conservative treatment. The patient had not had any significant lymphedema. On physical examination, the patient had numerous isolated and translucent vesicles and bullae of the inferior left nipple (Figs.1, 2). They measure 2 to 3 mm in diameter. No lymphedema was present also. We performed biopsy from lesions that showed numerous dilated lymphatics, edema and mononuclear inflammatory cells throughout the papillary and reticular dermis (Fig. 3). With these clinical and histological findings the patient was diagnosed as cutaneous lymphangiectasis.

Some of the lesions were treated with cryosurgery and others were drained and then treated with electrocautery. Cryotherapy freezes these lesions with liquid nitrogen (-195.8°:). Cryotherapy was applied to the skin twice for 20 seconds. Daily wound care consisted of gentle cleansing with povidone iodine and application of mupirocin ointment. At 8 weeks, the wound had completely re-epitheliazed. The wounds healed without scarring and there was no evidence of recurrence in subsequent 2 months.


Acquire lymphangiectasis is a condition in which dilated superficial lymphatics develop after damage to previously normal lymphatics. Acquired lymphangiectasis has been reported as clinically and histologically indistinguishable from congenital lymphangioma circumscriptum and is often reported in the literature as lymphangioma circumscriptum or acquired lymphangiomas [2, 3, 4, 5].

Cutaneous lymphangiectasis (CL) represents acquired vesicular dilatation of lymphatic channels secondary to an external cause with no evidence of true tumor formation. It has been associated mostly with the treatment of malignancies of breast and cervix and is often coexistent with lymphedema [1, 6, 7, 8]. There have also been reports of CL after treatment of myxoid chondrosarcoma and bronchial carcinoid [4, 9]. It has been documented after surgery alone, surgery and irradiation, and irradiation alone [8, 10]. Other reported cases without lymphedema include scarring from scrofuloderma, scleroderma, and cirrhosis [11, 12, 13].

Acquired lymphangiectasis has been reported in the literature with increased frequency in the past 20 years. This is most likely the result of increased surgical excision, surgery and radiation therapy for certain cancers. This condition has been documented to occur after surgical excision, surgery and irradiation and irradiation alone [3, 4, 10]. In our case, new lesions of lymphangiectasia ceased to develop after the conservative treatment. Although AL has been documented to occur after surgical intervention alone, we believe that x-ray therapy is a major contributor in its pathogenesis because the main site of injury of x-ray therapy is a major contributor in its pathogenesis, the site of injury from x-ray therapy is at the junction the fat and reticular dermis [8, 14]. This damage most likely causes fibrosis and lymphatic obstruction at the base of the reticular dermis and an accumulation of lymph fluid in the dermal lymphatics with resultant increased pressure [8]. This can then lead to sacular dilation of the superficial lymphatic channels with subsequent vesicle formation. The cutaneous lesions can range from clear, fluid-filled blisters to smooth, flesh-colored nodules, often appearing along an incisional scar. Coexisting lymphedema is present in most patients with acquired lymphangioma. Patients can present with localized wetness or copious drainage of clear or milky fluid from ruptured vesicles. Clinically, lymphangiectasia consists of several clusters of translucent, thick-walled, fluid-filled vesicles. The vesicles typically measure 2-10 mm in diameter. The affected area appears to be speckled by numerous translucent vesicles with normal-appearing skin among the lesions. Some lesions may become pedunculated with a hyperkeratotic verrucous surface mimicking a wart. The physical findings of our case were the patient had numerous isolated and translucent vesicles of the inferior left nipple area.

They measure 2-3 mm in diameter. On microscopic examination, large, dilated lymph vessels lined by a single layer of endothelial cells characterize lymphangiectasis. They are usually found in the papillary dermis and the reticular dermis. Involvement in the deeper dermis is rare. At times, acquired lymphangiectasis grow above the level of adjacent skin. The histological findings of our case were consistent with these features, the numerous dilated lymphatics, edema and mononuclear inflammatory cells throughout the papillary and reticular dermis.

Complications of AL include leakage of the vesicles, recurrent cellulites, and pain [15, 16]. Acquired lymphangiectasis is not precancerous, although there is one reported case of a squamous cell carcinoma arising in lymphangioma circumscriptum [17]. This entity is different from the Stewart-Treves syndrome of lymphangiosarcoma developing in the setting of post-mastectomy lymphedema. Edematous and ecchymotic plaques progressing to red to purple nodules characterize lymphangiosarcoma [1].

Treatment for lymphangiectasis can be difficult, but it is important because of the risk that ruptured vesicles may provide a portal of entry for infection and subsequent cellulites. To prevent superinfection of ruptured vesicles, cleansing the affected area daily with topical antibacterial agents and applying mupirocin ointment or silver sulfadiazine cream are advisable. Many surgical treatment modalities have been advocated in the care of lymphangiectasis; these modalities include electrodesiccation, laser therapy, sclerotherapy, cryotherapy, and surgical excision. Daily compression through bandaging or hosiery in accessible areas has yielded acceptable results. In addition, laser therapy has also been shown to be an effective treatment.

Various types of lasers have been used for this treatment, including the argon, tunable dye and CO&sub2; [1, 18, 19, 20]. There can be recurrences with all these treatments, and some may leave significant scarring. Our patient received treatment using the cryosurgery and some of them were drained and treated with electrocautery. Daily wound care consisted of gentle cleansing with povidone iodine and application of mupirocin ointment. At 8 weeks, the wound had completely re-epitheliazed. The wound was healed without any tissue scar and evidence of recurrence in following 2 months after re-epitheiazation.

Acquired lymphangiectasis is an important complication of radiation therapy and surgical intervention for malignancy and probably not as rare as once believed. Although this lesion has been described as histologically indistinguishable from lymphangioma circumscriptum, we believe these two conditions have true histologic differences in addition to their differing pathophysiology and clinical presentation. Acquired lymphangiectasis is an acquired dilation of lymphatics and can be associated with lymphedema after surgery and/or radiation therapy. Clinicians should be familiar with is presentation and pathogenesis since its complications can be significant. In addition, lesions are often cosmetically undesirable. The treatment is relatively simple, though recurrences are not uncommon.


1. Celis, AV, Gaughf CN, Sangueza, OP, Gourdin, FW. Acquired lymphangiectasis. South Med J. 1999 Jan;92(1):69-72. PubMed
2. Leshin B, Whitaker D, Foucar E. J Am Acad Dermatol. 1986 Nov;15(5 Pt 2):1117-9. PubMed
3. Ambrojo P, Cogolluda EF, Aguilar A, Sanchez Yus E, Sanchez de Paz F. Cutaneous lymphangiectases after therapy for carcinoma of the cervix--a case with unusual clinical and histological features. Clin Exp Dermatol. 1990 Jan;15(1):57-9. PubMed
4. Moon SE, Youn JI, Lee YS. Acquired cutaneous lymphangiectasia. Br J Dermatol. 1993 Aug;129(2):193-5. PubMed
5. Abu-Hamad A, Provencher D, Ganjel P, Penalver M.Lymphangioma circumscriptum of the vulva: case report and review of the literature. Obstet Gynecol. 1989 Mar;73(3 Pt 2):496-9. PubMed
6. Kaya TI, Kokturk A, Polat A, Tursen U, Ikizoglu G. A case of cutaneous lymphangiectasis secondary to breast cancer treatment. Int J Dermatol. 2001 Dec;40(12):760-1. PubMed
7. Giannelli V, Rockley, PF. Acquired lymphangiectasis following mastectomy and radiation therapy--report of a case and review of the literature. Cutis. 1996 Oct;58(4):276-8. Review. PubMed
8. Mallett, RB, Curley, GK, Mortimer, PS. Acquired lymphangioma: report of four cases and a discussion of the pathogenesis. Br J Dermatol. 1992 Apr;126(4):380-2. PubMed
9. Ziv R, Schewach-Miller M, Trau U. Lymphangiectasia. A complication of thoracotomy for bronchial carcinoid. Int J Dermatol. 1988 Mar;27(2):123. No abstract available. PubMed
10. Fisher I, Orkin M. Acquired lymphangioma (lymphangiectasis). Report of a case. Arch Dermatol. 1970 Feb;101(2):230-4. No abstract available. PubMed
11. Di Leonardo M, Jacoby RA. Acquired cutaneous lymphangiectasias secondary to scarring from scrofuloderma.J Am Acad Dermatol. 1986 Apr;14(4):688-90. PubMed
12. Tuffanelli DL. Letter: Lymphangiectasis due to scleroderma. Arch Dermatol. 1975 Sep;111(9):1216. PubMed
13. Garcia-Doval I, de la Torre C, Losada A, Ocampo C, Rodriguez T, Cruces MJ. Acquired cutaneous lymphangiectasia in a patient with cirrhotic ascites. J Eur Acad Dermatol Venereol. 1999 Sep;13(2):109-12. PubMed
14. Mortimer PS, Simmonds RH, Rezvani M, Robbins ME, Ryan TJ, Hopewell JW. Time-related changes in lymphatic clearance in pig skin after a single dose of 18 Gy of X rays. Br J Radiol. 1991 Dec;64(768):1140-6. PubMed
15. Peachey RD, Lim CC, Whimster IW. Lymphangioma of skin. A review of 65 cases. Br J Dermatol. 1970 Nov;83(5):519-27. PubMed
16. Bhattacharyya NC, Yadav K, Mitra SK, Pathak IC. Lymphangiomas in children. Aust N Z J Surg. 1981 Jun;51(3):296-300. PubMed
17. Wilson GR, Cox NH, McLean NR, Scott D. Squamous cell carcinoma arising within congenital lymphangioma circumscriptum. Br J Dermatol. 1993 Sep;129(3):337-9. No abstract available. PubMed
18. Weingold DH, White PF, Burton CS. Treatment of lymphangioma circumscriptum with tunable dye laser. Cutis. 1990 May;45(5):365-6. PubMed
19. Eliezri YD, Sklar JA. Lymphangioma circumscriptum: review and evaluation of carbon dioxide laser vaporization. J Dermatol Surg Oncol. 1988 Apr;14(4):357-64. PubMed
20. Bailin PL, Kantor GR, Wheeland RG. Carbon dioxide laser vaporization of lymphangioma circumscriptum. J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):257-62. PubMed

Dermatology Online Journal

Friday, September 08, 2006

Primary Intestinal and Thoracic Lymphangiectasia: A Response to Antiplasmin Therapy

Primary Intestinal and Thoracic Lymphangiectasia: A Response to Antiplasmin Therapy


Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy.

However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Key Words: lymphangiectasia • anti-plasmin • gastrointestinal bleedingIntroduction

Primary lymphangiectasia is a congenital disorder of the lymphatic system characterized by marked ectasia of the lymphatic vessels resulting in obstruction and leakage of lymph fluid.1 Intestinal lymphangiectasia is characterized by a protein-losing enteropathy and is diagnosed definitively by small bowel biopsy demonstrating dilated lymphatics in the mucosa, submucosa, and serosa in the absence of coexistent inflammation.24 Symptoms include diarrhea, peripheral edema, lymphedematous limbs, general malaise, and weight loss.2,5 In pulmonary or thoracic lymphangiectasia, dilation of lymphatics in the visceral pleura as well as interlobular septa result in chylothoraces, which may lead to respiratory compromise or failure.1 Intestinal and thoracic lymphangiectasia may occur in isolation or simultaneously in the same patient as part of a generalized lymphatic dysplasia.6

Treatments described for lymphangiectasia have included corticosteroids for patients with primary inflammatory conditions,7 dietary modifications,8 surgical resection for isolated lesions,9 octreotide,10,11 and antiplasmin therapy.12 Successful management with these treatment modalities has been variable with no evidence of specific groups of patients responding to a particular treatment.

We report a case of lymphangiectasia associated with intestinal bleeding, a finding that is not commonly described.13 The protein-losing enteropathy was refractory to total parenteral nutrition and a low-fat medium-chain triglyceride diet as well as octreotide, with improvement after starting antiplasmin therapy.

Case Report

A 14-year-old previously healthy girl was transferred from a peripheral hospital with a microcytic anemia requiring transfusion and a large left-sided pleural effusion. She had a 3-week history of fatigue, abdominal pain, nausea, and vomiting, accompanied by a 3-kg weight loss and grossly bloody stools. On physical examination, her heart rate was 119 beats/min, respiratory rate 36 breaths/min, blood pressure 97/46 mm Hg, and oxygen saturation 99% in room air. She had marked pallor and periorbital edema. Chest examination revealed decreased breath sounds on the left side. A grade II/VI systolic ejection murmur was heard over the left lower sternal border with normal heart sounds. Abdominal examination revealed evidence of ascites with no organomegaly.

There was notable peripheral edema but no evidence of lymphadenopathy. Initial laboratory investigations showed a hemoglobin of 58 g/L and platelets of 248 x 109/L. White blood cell count was 5.9 x 109/L with lymphopenia (0.36 x 109/L lymphocytes). Albumin was 19 g/L with a total protein of 34 g/L and immunoglobulins G, A, and M of 2.4 g/L (normal range: 7.2–15.8 g/L), 0.5 g/L (normal range: 0.5–3.5 g/L), and 0.7 g/L (normal range: 0.2–2.6 g/L), respectively. Urinalysis showed no evidence of proteinuria. The erythrocyte sedimentation rate, amylase, urate, lactate dehydrogenase, transaminases, bilirubin, and -fetoprotein levels were normal with stools positive for blood and markedly elevated stool -1-antitrysin levels. Chest radiograph showed a large left-sided pleural effusion and a small right-sided effusion (Fig 1).

Computerized tomography and magnetic resonance imaging of the chest and abdomen revealed diffuse abnormalities in the mediastinal fat, thickened bowel loops, and mild ascites but no focal mass or lymphadenopathy. An echocardiogram was normal. An endoscopic examination of the small bowel showed diffuse bowel wall thickening with distal nodularity of the ileum. A lymphangiogram demonstrated delayed transit with normal subdiaphragmatic nodal architecture and no entry into the cisterna chyli or thoracic duct. Thorascopic biopsy of the mediastinal lesion showed grossly fatty vascular tissue that appeared necrotic microscopically without evidence of malignancy. Upper gastrointestinal endoscopy revealed gross white nodules consistent with lymphangiectasia. No focal bleeding sites were seen. Microscopically, there was focal lymphangiectasia in the duodenal cap and gastric antrum. Thoracentesis of the left hemithorax drained 1.8 L of serous fluid with pH 7.0, protein of 20 g/L, glucose of 5.4 mmol/L, and elevated triglycerides of 0.92 mmol/L with chylomicrons present. The white blood cell count of the fluid was elevated at 231 cells/mm3 with a lymphocytic predominance. Routine and mycobacterial cultures were sterile. Cytology showed no malignant cells. Bilateral bone marrow aspirates and biopsy were normal. A gallium scan was normal.

The patient was started on total parenteral nutrition and complete bowel rest. Her albumin remained persistently low despite weekly albumin infusions, and her chest tube continued to drain 1 to 2 L daily. Persistent gastrointestinal bleeding resulted in blood transfusions approximately every 2 weeks. A red blood cell scan and Meckel’s scan were negative with repeat upper and lower intestinal endoscopies showing no signs of active bleeding. Subcutaneous octreotide therapy was initiated 30 days into hospitalization. Although the chest pathology improved with decreased output from the chest tubes, the enteropathy persisted. Repeat endoscopy 5 weeks into hospitalization revealed some pathologic improvement in the duodenum, but multiple focal areas of lymphangiectasia were seen in the terminal ileum. A low-fat medium-chain triglyceride diet was instituted for 4 weeks but did not lead to any improvement.

Based on a report showing benefit with antiplasmin therapy, a trial of tranexamic acid (1000 mg by mouth, 3 times daily) was initiated 2.5 months after presentation (Fig 2). At the time, D-dimer levels were elevated at 1770 ng/mL (normal: 0–449 ng/mL) with normal partial thromboplastin time and international normalized ratio. One month later, her albumin had improved to 24 g/L and her immunoglobulin G level was 5.4 g/L. She remained clinically stable for 10 months with normal levels of serum albumin and immunoglobulin G, and she did not have additional intestinal bleeding. Fourteen months after her initial presentation, an exacerbation of her condition occurred with recurrent transfusion dependent lower gastrointestinal bleeding and hypoalbuminemia requiring daily albumin infusions.

Repeat endoscopic biopsies again demonstrated lymphangiectasia throughout the small bowel as well as multiple areas of mucosal petechiae. After a 1-month period of parenteral nutrition and bowel rest, increasing the dose of octreotide, and increasing the dose of tranexamic acid to 6 g/d, her condition stabilized with resolution of the intestinal bleeding.


Lymphangiectasias are disorders characterized by abnormal, dilated lymphatics. There is wide variation in the age of onset and extent of disease. Primary lymphangiectasia is a congenital malformation, with the age of presentation ranging from in utero onset to early adulthood. Lymphangiectasia may also be secondary to lymphatic damage from other processes including lymphoma, radiotherapy, and constrictive pericarditis. Although lymphangiectasia can be isolated to the gastrointestinal or pulmonary systems, generalized disease usually shows a predominance of intestinal manifestations.14 We describe a case showing some of the classic features of lymphangiectasia including chylous pleural effusions, lymphopenia, hypoalbuminemia with enteric protein loss, and hypogammaglobulinemia. A thorough investigation excluded potential underlying causes. This case also describes an association with intestinal bleeding thought to be related to latent lymphatic-venous anastomoses, which can rupture under abnormally high lymphatic pressure.13 There was marked clinical improvement, as measured by serum albumin, immunoglobulin levels, and resolution of intestinal bleeding, with the initiation of antiplasmin therapy.

The rarity of lymphangiectasia and the wide variation in its clinical presentation provides a challenge in identifying appropriate therapy. Supportive therapy including albumin infusions, diuretics, thoracentesis, and paracentesis provides transient relief of symptoms. Surgical resection is an option for limited disease of the small bowel.9,15 Dietary modifications are aimed at controlling symptoms and consequences of lymphatic obstruction but not at modifying the underlying disease process. Restriction of dietary fat results in reduction in lymph flow and subsequent leak of protein. Low-fat medium-chain triglyceride diets have been used as sole therapy as well as a part of other treatment regimens. These triglycerides are not reesterified within intestinal cells, thereby bypassing enteric lymphatics. In most patients, dietary modifications need to be continued indefinitely to control symptoms.8 Although it is generally accepted that corticosteroids do not have a role in the treatment of lymphangiectasia, they have been used with success in patients with elevated acute phase reactants, suggesting that there may be a subset of patients with underlying inflammatory disease who may respond to corticosteroids.7,16

Octreotide acetate is a long acting somatostatin analog that may aid in the reduction of lymphatic losses in lymphangiectasia through a variety of mechanisms including reduction of thoracic duct lymph flow17 and reducing lymph fluid excretion in enteric vasculature.18 Octreotide has been reported to be successful in 2 cases refractory to other therapeutic modalities.10,11 Increased fibrinolytic activity, which causes intestinal protein loss, has been proposed as a mechanism responsible for several conditions characterized by protein-losing enteropathy. In a rat protein-losing enteropathy model as well as in patients with Menetrier’s disease and hypertrophic gastritis, Kondo et al19 demonstrated increased tissue fibrinolytic activity in gastric mucosa biopsy specimens.

Treatment with antiplasmin therapy, tranexamic acid, led to a resolution of symptoms, laboratory evidence of enteric protein loss, and, in animal models, a normalization of tissue fibrinolytic activity.20 Based on these studies and case reports, Mine et al12 treated a 35-year-old woman with intestinal lymphangiectasia and increased plasma fibrinolytic activity, as measured by euglobin lysis time, with tranexamic acid. The mechanism of action of tranexamic acid has been shown to involve inhibition of conversion of plasminogen to plasmin as well through weak noncompetitive inhibition of plasmin.

This patient showed a dramatic clinical response within 6 weeks that was sustained over 8 years, with clinical exacerbations occurring only with discontinuation of the drug and remitting with reinstituting therapy. Two different authors reported 3 subsequent patients, with and without increased plasma fibrinolytic activity, who did not benefit from antiplasmin therapy, and there has not been a subsequent reported case of lymphangiectasia that responded to this therapy. Mine concluded that there is a subset of patients with lymphangiectasia, who may have increased tissue or plasma fibrinolytic activity and may respond to antiplasmin therapy.

Our case represents the second apparent beneficial use of this therapy. The elevated D-dimers in our patient may be reflective of increased fibrinolytic activity, which may have a causative role in the protein-losing enteropathy. Tranexamic acid has been used successfully in hereditary hemorrhagic telangiectasia,21 and this condition is also characterized by lesions with increased local fibrinolytic activity caused by an increase in tissue plasminogen activator.22 It is plausible that the multiple areas of mucosal bleeding in our patient represent lesions with increased fibrinolytic activity, and that tranexamic acid modulates the effect of tissue fibrinolysis in these areas.

There may be a subset of patients with lymphangiectasia who have gastrointestinal bleeding from diffuse areas of local hyperfibrinolysis and may respond to antiplasmin therapy. Although it can be argued that our patient’s initial improvement was coincidental to initiation of therapy with tranexamic acid as spontaneous remissions can occur, the timing and nature of the improvement was similar to Mine’s patient.

The resolution of gastrointestinal bleeding and the lack of need for any red blood cell or albumin infusions are striking. Our patient has had an exacerbation of her condition which subsequently improved and ongoing lymphopenia which reflects the persistence of the anatomic abnormalities of the lymphatics despite therapy. D-dimers remain elevated, which may be indicative of a persistent fibrinolytic state. The side effect profile of tranexamic acid includes gastrointestinal upset and retinal changes,23 which have not been demonstrated in ongoing surveillance in our patient. Although the long-term outcome of our patient is unclear, it is evident that the improvement in her condition was most likely related to tranexamic acid therapy.

This case underscores the fact that lymphangiectasia is a heterogeneous and poorly understood condition. Some patients with this condition, particularly those with diffuse gastrointestinal bleeding, may respond to antiplasmin therapy. A multicenter surveillance study may aid in our understanding of this uncommon and heterogeneous disorder and provide a more systematic approach to treatment of this complex clinical problem.

Division of Paediatric Medicine The Hospital for Sick Children University of Toronto Toronto, Ontario, Canada M5G 1X8

Joanna E. MacLean, MD, Eyal Cohen, MD and Michael Weinstein, MDDivision of Paediatric Medicine The Hospital for Sick Children University of Toronto Toronto, Ontario, Canada M5G 1X8