Case 1: A 8 year old girl presented with history of recurrent small bowel diarrhea and anasarca from the age of 5 years.This illness was not associated with fever, vomiting, abdominal pain, rash, arthralgia or urinary symptoms.There was no history of contact with tuberculosis. The present hospitalization was for swelling of hands and feet which had increased with worsening of diarrhea. She was first born to non-consanguineous parents, with a birth weight of 3.5 kgs and was apparently well till 5 years of age. On examination, she had generalized anasarca and her vitals and systems examination were normal. She weighed 21.6 kgs as against 26 kg. Biochemical and hematological profile is summarized in Table I. USG abdomen showed ascites and bilateral pleural fluid. Barium meal and follow through demonstrated coarse mucosal folds and flocculation in the small intestine. Her lipid profile was normal except for low HDL levels. The characteristic "snow flake appearance" of the duodenum was seen on upper gastrointestinal endoscopy (Fig. 1). Dilated lymphatics, the typical histopathological feature of IL was reported in the duodenal biopsy (Fig .2). She was given medium chain triglycerides (MCT) based diet supplemented with albumin transfusions. Diarrhea and anasarca improved over 2 weeks but she succumbed later at the age of 8 years and 6 months due to an intercurrent viral illness.

Fig. 1 Upper gastrointestinal endoscopy of duodenum showing the snow flake appearance.	Fig. 2 Histopathology of small intestine showing the grossly dilated lymphatics in lamina propria the hallmark of intestinal lymphangiectasia.

TABLE I



Clinical and Laboratory Details of 4 Children with Primary Intestinal Lymphangiectasia

Case 2: A 9 year old female, presented with anasarca and recurrent loose stools suggestive of small bowel diarrhea for 20 days. She was first born of non consanguineous parents and remained apparently well till 9 years of age except for body asymmetry. The right side of her body including her extremities and face was noted to be more prominent than the left. She had minimal motor delay and poor scholastic performance. On examination her face was dysmorphic with depressed nasal bridge, puffy eyelids and small mouth. She had asymmetrical generalized edema with lymphedema involving the right side of her body including the genitalia and both feet. Her blood pressure and systems examination were normal. A diagnosis of Hennekman Syndrome was made based on the phenotypic features. Investigations are summarized in Table I. She was managed with albumin transfusions, low fat with MCT diet and genetic counseling was offered to the parents.

Case 4: A 5 year old male presented with history of recurrent small bowel diarrhea associated with anasarca since 1 year of age. He was hospitalized thrice for similar complaints. There was no rash, arthralgia, joint pains or contact with tuberculosis. He was alert and had anasarca. Investigations are shown in Table I. He was given MCT based diet and albumin infusions following which he responded and is on regular follow up.

Primary intestinal lymphangiectasia (PIL) or Waldmann’s disease is characterized by malformation of lymphatics leading to obstruction, rupture and leak of lymph fluid into the bowel lumen resulting in hypoalbuminemia, lymphopenia and hypogammaglobulinemia(3). The clinical features of PIL are bilateral lower limb edema, ascites, and chronic diarrhea which was seen in all our 4 cases. The lung, uterus and conjunctiva may also be involved in IL(4,5). Necrolytic migratory erythema, osteomalacia, recurrent gastrointestinal bleeding and recurrent hemolytic uremic syndrome can occur in patients with PIL(3). PIL is generally diagnosed before 3 years of age but may be diagnosed in older children and adults as in our series, where 3 children were diagnosed beyond the age of 5 years(6). The etiology of PIL still remains unknown.

The syndromes linked with intestinal lymphangectasia include Von Recklinghausen, Turner, Noonan, Klippel Trenaunay, Hennekam and Yellow nail(3). In our case series, one child had features suggestive of Hennekam syndrome (characteristic facial abnormalities, developmental delay, severe limb and facial lymphedema)(7). IL has been associated with celiac disease. Diagnosis of intestinal lymphangiectasia is established by the characteristic histology of grossly dilated lymphatics seen in the lamina propria of the small bowel (duodenum/jejunum/ileum). The villi may be distorted and enlarged but usually without atrophy(6). Endoscopy may be normal if the involvement is patchy and in such cases videocapsule endoscopy helps in localization(8). The immunological abnormalities reported in PIL are reduced immunoglobulin levels (IgG, IgA, IgM), low CD 4+ T cells, lymphocytopenia, skin allergy and graft rejection(3,9). In our series only 2 children had low immunoglobulin levels.

Life long dietary modification with high protein, restricted fat substituted with medium chain triglycerides (MCT) and vitamin supplements remains the cornerstone in the management of PIL. Exclusion of long chain fatty acids prevents the engorgement and rupture of malformed lymphatics while MCT get directly absorbed into the portal venous circulation(3). In case of poor response to this treatment partial or total parenteral nutrition should be considered. Other treatment modalities described in literature with variable efficacy include antiplasmin therapy, octreotide, corticosteroids, small bowel resection, albumin infusions, peritoneo venous shunt (Levine) and intestinal transplant(3).

Dr Meera Govindarajan, Pathologist, R & D Diagnostic Laboratory, Chennai for histopathology.

1. Waldmann TA, Steinfeld JL, Dutcher TF, Davidson JD, Gordon RS. The role of gastrointestinal system in "Idiopathic hypoproteinemia". Gastroenterology 1961; 41: 197-207.

2. Fang YH, Zhang BL, Wu JG, Chen CX. A primary intestinal lymphangiectasia patient diagnosed by capsule endoscopy and confirmed at surgery : A case report. World J Gastroenterol 2007;13: 2263-2265.

3. Vignes S, Bellanger J. Primary intestinal lymphangiectasia (Waldmann’s disease).Orphanet Rare Dis 2008; 3: 5.

4. Lee WS, Boey MCC, Goh TAY, Chang KW, Iyngkaran N. Intestinal lymphangiectasia – A report of three Chinese children in Malaysia . Singapore Med J 1998; 39: 418-421.

5. Mucuke J, Hoepffner W, Scheerschmidt G, Gornig H, Beyreiss K. Early onset lymphedema, recessive form – a new form of genetic lymphedema syndrome. Eur J Pediatr1986; 154: 195-198.

6. Tift WL, Lloyd JK. Intestinal lymphangiectasia long term results with MCT diet. Arch Dis Child 1975; 50: 269-276.

7. Hennekam RC, Geerdink RA, Hamel BC, Hennekam FA, Kraus P, Rammeloo JA, et al. Autosomal recessive intestinal lymphangiectasia and lymphedema with facial anomalies and mental retardation. Am J Med Genet 1989; 34: 593-600.

8. Chamouard P, Nehme-Schuster H, Simler JM, Finck G, Baumann R, Pasquali JL. Videocapsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia. Dig Liver Dis 2006; 38: 699-703.