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.

Introduction

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].

Treatment

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.)

Surgery

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

Standard procedure:

Small bowel resection.

Contraindications

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,

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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.

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