Summary A 7-month-old boy was referred to the Paediatric Gastroenterology Department with protracted diarrhoea, persistent hypo-albuminemia, electrolyte disbalance and failure to thrive. He had presented 2.5 months earlier with abdominal distention, pedal oedema, and generalized pallor. A mature cystic teratoma was found after a CT of the abdomen, followed by surgical resection. The histology was compatible with the above and the ascitic fluid had elements of a transudate. The initial oncologic investigations identified a low IgG serum level, with normal IgA and IgM, as well as low lymphocytes. Urine protein loss was out ruled. An oesophagus-gastro-duodenoscopy showed whitish mucosa in duodenum. Colonoscopy up to transverse colon was normal. The histology showed normal oesophagus. The stomach had vascular ectasia, mild oedema and congestions within the lamina propria. D1 normal. D2 small areas of the lamina propria appeared to be oedematous within the villous structures and a focal area of haemorrhage was noted. There was no obvious evidence of generalised dilated lacteals. The colonic biopsies were normal. He had a mildly raised faecal alfa-1-antitrypsin with normal faecal elastase. The initial management included Total Parental Nutrition and albumin infusions, followed by subcutaneous octreotide and tranexamic acid to reduce the albumin loss. After the patient’s albumin stabilized and gained weight, a low-fat diet with a MCT high-containing formula were started. At discharged the patient still required SC octreotide to keep normal level of serum albumin, which continued to receive for 12 months. After 1 year of treatment, the SC Octreotide was weaned off gradually until discontinued. The patient kept an adequate level of Albumin, his lymphopenia and hypogammaglobulinemia was resolved, and he thrived accordingly. He has been kept on low fat diet with high MCT formula to date. Accidentally, the patient ingested food with LCT (cross contamination) and developed profuse, auto-limited diarrhoea for 5 days without changes in his biochemistry. It was decided that the patient should remain on low fat diet for the foreseeable future.

Background Protein loosing enteropathy in children is a rare condition with major repercussions in nutrition and development. In early stages of life, congenital diarrhoea and cow’s milk allergy are the main causes. Coeliac disease and Cystic Fibrosis could also debut with such features. Intestinal lymphangiectasia, primary or secondary, is a rare condition without an established epidemiology to date. There is no predominance of gender or race. The cases reported have been of sporadic origin {1} without an identified genetic aetiology.

The mean age of diagnosis is 12 years of age [1]. Primary causes include vascular malformations of childhood [2} and secondary causes follow a long list of pathologies that could result in lymphatic drainage blockage. The resulting ectasia causes dilatation of the lymphatics with loss of lymph leakage into the bowel leading to hypoproteinaemia, oedema, lymphocytopenia, hypogammaglobinaemia – accompanied with immunological abnormalities – as well as micronutrients deficiency including calcium, iron and fat-soluble vitamins, among others {4}

The symptoms of Intestinal Lymphangiectasia may include chronic diarrhoea, limb oedema, ascites and pleural effusions. Chylothorax could be a rare presentation {2}.

Diagnosis is made through endoscopy and histological findings that confirmed the dilated lymphatics.

The management includes dietary modification with high doses of medium-chain triglycerides, total parenteral nutrition, albumin infusions and, in some series, octreotide, tranexamic acid, corticosteroids and surgery have been reported {3}.

We report a case of intestinal lymphangiectasia clinically presenting as persistent hypoalbuminemia, protracted diarrhoea and failure to thrive. The endoscopic findings were in keeping with the disease and the management of this case involved the participation of gastroenterologist, immunologist and dietitians.

Case report A 7-month-old boy who was diagnosed with a mature cystic teratoma after presenting acutely ill to his local hospital. His initial complaints were swollen abdomen and feet, pallor and vomiting. Term born via caesarean, he had a hyper-sensitive gag reflex and frequent episodes of vomiting. During his recovery from surgery he developed diarrhoea, up to 10 a day, with persistent hypoalbuminemia that did not improve to albumin infusions and diuretics, as well as electrolyte disturbances that required often supplementation. At admission his weight was static but progressively he started to emaciate.

Treatment Initially the patient received albumin infusions and diuretics. He remained on breastfeeds and age-appropriate purees. Additionally, he was started on enteral feeds via NG with an extensively hydrolysed formula with MCT that he failed to tolerate (vomiting). After referral to Gastroenterology he was started on total parental nutrition. Initially the lipids were restricted due to the severity of the liver derangement and progressively introduced later when the latter was resolved. However, despite adequate levels of nutrients and resolution of diarrhoea and vomiting his albumin levels remained low requiring albumin infusions. After a multidisciplinary discussion with the Immunology department and Dietitians the patient was started on subcutaneous octreotide looking to lower the lymph flow and losses in the bowel. He was started at a 100µg/kg dose, twice a day. During the initial 3 weeks of treatment the patient still required weekly albumin infusions. Tranexamic acid was later started without satisfactory results 1 week after treatment and therefore it was stopped.

Outcome and follow-up At discharge the patient was reviewed weekly in the Day-case unit with albumin measurements that remained as of discharge between 17 and 20 for 4 weeks. These static changes led to the decision to stop the octreotide. Within 7 days the patient gained 2 kg in average and required an intravenous infusion of albumin as it dropped to 13 with clinically evident oedema. He was also re-commenced on octreotide SC OD only. The following 4 weeks showed progressive normalization of albumin levels building up to 40 when titration of octreotide by 20 mcg/weekly was started. The results of the titration were favourable and the patient kept normal albumin levels, without diarrhoea until complete withdrawal of Octreotide.

The patient achieved full growth (weight and height) for his age, adequate neurological development and normalization of all his serological values (immunoglobulins and lymphocytes).

Accidentally, the patient ingested food with LCT (cross contamination) and developed profuse, auto-limited diarrhoea for 5 days without changes in his biochemistry. It was decided that the patient should remain on low fat diet for the foreseeable future.

Discussion Intestinal lymphangiectasia still possess a challenging physiopathology to diagnose and treat. Multiple case reports and cohort studies have summarized the diagnostic features of primary and secondary IL reflected in serology and endoscopy {1, 5, 6}.

The limitation on large series makes the different treatment modalities more of anecdotical than factual experience. However, adequate response in both the short and long term have been achieved with the use of octreotide. Table 2 summarizes the different studies and doses used (when available).

Tranexamic acid was only reported in one publication with octreotide given simultaneously. The treatment was abandoned due to lack of response.

In the adult series, nutritional management (parenteral and enteral) has been the most frequently used, with mixed results. The largest review of published articles has concluded that the long term of nutritional supplementation with MCT oils was reflected in the improvement of the immune system and less frequent admissions for albumin infusions {2}. This was also seen in the largest paediatric cohort published recently {5}.

Our patient received all the treatment suggested by literature in unison. The nutritional support improved the weight and height of the patient. Tranexamic acid did not make a difference in the frequency of albumin infusions. Octreotide (180 mcg SC BD) with nutritional support (high protein, low fat, high MCT concentration formula and low-fat diet) for 12 and 18 months (after discharge), respectively, had the most significant results (normalization of albumin levels, immunoglobulins and lymphocytes).

Conclusion IL is a challenging diagnosis and requires a multidisciplinary team support to achieve adequate a satisfactory treatment. The results are widely variable perhaps due to the spectrum of the disorder that has not been fully described given he rareness of the condition.

Octreotide has shown to be a promising therapy for this disorder, however more extensive studies and cohorts are required. The most satisfactory treatment reported to date is a low-fat diet and high-MCT supplements.

References

1. Mohamed J. Alshikho. Intestinal lymphangiectasia: insights on management and literature review. 2016. DOI: 10.12659/AJCR.899636

2. Umar SB, DiBaise JK: Protein-losing enteropathy: case illustrations and clinical review. Am J Gastroenterol 210;105(1):43–49; quiz 50.

3. Guandalini S, Dhawan A, Branski D. Textbook of paediatric gastroenterology, hepatology and nutrition. 2016. Pp 577.

4. Desai AP, Guvenc BH, Carachi R. Evidence for medium chain triglycerides in the treatment of primary intestinal lymphangiectasia. Eur J Pediatr Surg 2009;19(4):241–5.

5. Kwon Y, Kim MJ. The update of treatment for primary intestinal lymphangiectasia. 2021. Pediatr Gastroenterol Hepatol Nutri. 2021 Sep;24(5):413–422. DOI: 10.5223/pghn.2021.21.5.413

6. Kwon Y, Kim ES, Choe YH, Kim MJ. Individual approach for treatment of primary intestinal lymphangiectasia in children: single centre experience and review of literature. BMC Pediatr 2021 Jan 7;21. DOI: 10.1186/s12887-020-02447-5