Refractory primary intestinal lymphangiectasia effectively managed with subcutaneous octreotide
- 1 Gastroenterology, Epsom and Saint Helier University Hospitals NHS Trust, Epsom, UK
- 2 Nutrition, Epsom and Saint Helier University Hospitals NHS Trust, Carshalton, UK
- 3 General Surgery, Highgate Private Hospital, London, Highgate, UK
- Correspondence to Dr Amir Halim; amir.halim@nhs.net
Abstract
This case report describes a young man with a history of lymphoedema and long-standing gastrointestinal symptoms since childhood. After undergoing extensive investigations, he was diagnosed with primary intestinal lymphangiectasia (IL). The patient’s condition was refractory to conventional medium-chain triglyceride diet but responded well to treatment with subcutaneous octreotide. We have shown octreotide to be effective in improving the pathological effects of primary IL, associated with improved clinical well-being and serology, but it is not a curative therapy.
Case presentation
A man in his late 30s was referred by his general practitioner (GP) for investigation of unintentional weight loss over 6 months. He was diagnosed as having lymphoedema as a teenager. He had also suffered from bloating, loose stools and nausea for over 20 years and had been given a diagnosis of irritable bowel syndrome by his previous GP. There was no history of fever, night sweats or haematochezia. He was originally from the Indian subcontinent and moved with his family to the UK over 20 years ago. He recalls one of his siblings needed treatment for pulmonary tuberculosis (TB) when he was a child living in the Indian subcontinent. There was no significant family history. He did not take any drugs and had never smoked or drank alcohol. The patient denied high-risk activities (eg, intravenous drug use, unprotected sexual intercourse). He was a civil servant and frequently travelled to the Middle East for business. On initial assessment in clinic, he appeared cachectic with a low body mass index (BMI) of 17 kg/m2 and bilateral lower limb oedema.
Differential diagnosis
The potential differential diagnoses include Crohn’s disease, chronic intestinal infections (eg, Whipple’s disease, TB), lymphoma, pancreatic insufficiency, HIV-related enteropathy, nephrotic syndrome, chronic liver disease, thyrotoxicosis, coeliac disease, retroperitoneal fibrosis, congestive heart failure and autoimmune conditions such as systemic lupus erythematosus and sarcoidosis.1–3
Investigations
Blood tests revealed hypoalbuminaemia (albumin, 18 g/L) and lymphopenia (0.9×109/L). All other baseline haematology and biochemistry, including inflammatory markers, were normal. Virology, autoantibodies, TB quantiferon and coeliac screen were negative. Stool microscopy, culture and ova, cysts and parasites were negative. Faecal elastase and calprotectin levels were unremarkable. Urine was negative for protein. Plain chest film and abdominal ultrasound scan were normal. Colonoscopy and oesophago-gastro-duodenoscopy (figure 1) were both unremarkable. Duodenal biopsies (figure 2) and random colonic biopsies did not reveal any abnormalities. A full-body CT scan revealed small bowel oedema. Balloon enteroscopy revealed extensive small, white spots throughout the jejunum, and the mucosa appeared thickened and oedematous (figure 1). Jejunal biopsies (figure 2) and aspirate were obtained. Microscopy and culture of the jejunal aspirate did not identify any pathogens. Histological analysis of the biopsies showed dilated lymphatic vessels (figure 2) and confirmed a diagnosis of intestinal lymphangiectasia (IL). In the absence of any obvious precipitating cause, a diagnosis of primary IL was made.
Normal duodenum seen on oesophago-gastro-duodenoscopy (left). Enteroscopy (centre) showed thickened and oedematous jejunum with dilated lacteals appearing as multiple white spots, pathognomonic of intestinal lymphangiectasia. Video capsule endoscopy (right), performed 18 months after the patient commenced octreotide, showed no improvement in the appearance of jejunum.
Slides of the patient’s duodenal biopsy (top), showing normal villous architecture, and jejnual biopsy (bottom), showing distortion of villous architecture due to dilatation of the lymphovascular channels, in keeping with a diagnosis of intestinal lymphangiectasia.
Treatment
The patient was referred to the dietician and prescribed a low-fat/high-protein diet and medium- chain triglyceride (MCT) supplements. The patient’s symptoms and serum albumin failed to improve with MCT supplements and they were discontinued after 3 months. The patient was commenced on a 3-month trial of subcutaneous octreotide injections 200 µg twice a day.
Outcome and follow-up
Within 2 weeks of commencing octreotide, the patient reported a significant reduction in his bowel motions and his appetite had improved. After 3 months of taking octreotide, the patient’s BMI had improved from 17 kg/m2 to 19 kg/m2 and his oedema had resolved. Serum albumin increased from 18 g/L to 22 g/L. The patient’s lymphocyte count normalised within 12 months of commencing octreotide. He reported complete resolution of diarrhoea, reduced bloating and a significant improvement in general well-being. The patient continues treatment with long-term octreotide therapy and regular follow-up in his local Gastroenterology outpatient clinic. The patient had a video capsule endoscopy (VCE) 18 months after commencing octreotide therapy to reassess the jejunum. VCE found that there had been no change in mucosal appearances of the jejunum in comparison with initial enteroscopy. The patient continues to be followed up regularly, and on his most recent assessment in the outpatient clinic in February 2020, lymphocyte count (2.1×109/L), serum albumin (25 g/L) and BMI (20 kg/m2) remain stable. The patient does not report suffering any significant gastrointestinal symptoms on regular octreotide therapy.
Discussion
Primary IL, also known as Waldmann’s disease, is an extremely rare form of protein-losing enteropathy.1 It was first described by Waldmann et al in 1961 while investigating idiopathic hypoproteinaemia in children.4 The prevalence of the condition is not known due to its rare occurrence (and probable underdiagnosis). Cases have been reported sporadically across the world.1–6 It typically presents with symptoms associated with hypoproteinaemia and malabsorption in the first two decades of life, though in even rarer cases such as ours, it has been diagnosed as late as in the fourth decade.3 5 6
Primary IL has no known aetiology and is characterised by impaired drainage and dilatation of the small bowel lymphatic vessels.1–6 Increased dilatation of the lymphatic system leads to engorgement and occasional rupture of the lacteals, ultimately resulting in protein-rich lymph leaking into the lumen of the small bowel creating a state of malabsorption.1 2 6 Common symptoms or manifestations of primary IL include lymphoedema, weight loss, failure to thrive, diarrhoea, steatorrhoea, abdominal pain, fatigue, chylous ascites/effusions, hypoproteinaemia, hypoglobulinaemia, hypocalcaemia, lymphopenia, hypocholesterolaemia and vitamin D deficiency.1–3 5 6 B-cell lymphoma has been seen to develop in a few cases anywhere from 3 to 40 years after diagnosis.3
The variety of signs and symptoms associated with primary IL is one of the reasons it may be underdiagnosed. Primary IL remains a diagnosis of exclusion and in the absence of overt malabsorption presents similarly to irritable bowel syndrome. Investigations for causes of secondary IL (eg, Crohn’s, mesenteric TB, sarcoid, Whipple’s) must be undertaken before using the available radiological and biochemical investigations.
A diagnosis of IL can be established endoscopically using either balloon enteroscopy or capsule endoscopy.3 6 Enteroscopy is now the preferred diagnostic method over capsule endoscopy as biopsies for histopathological confirmation can be obtained.6 Capsule endoscopy remains a valuable tool for visualising areas of the bowel beyond the reach of endoscopy, enabling IL to be diagnosed when not visible on conventional endoscopy or in secondary care centres where balloon enteroscopy may not be readily available.3 6 Cross-sectional radiological imaging can be used to identify areas of the small bowel affected by IL (as it typically leads to mucosal thickening and oedema) that can be readily picked up by modalities such as contrast-enhanced CT.6 It must be noted that mucosal thickening and oedema are non-specific features that can also be a sign of inflammatory, infective or neoplastic processes of the bowel. However, CT would be useful and indicated for investigating/excluding these in the initial diagnostic phase.6 Other investigations that may be of use in the future include lymphoscintigraphy and technetium-labelled scintigraphy. Currently, they are relatively expensive tests, and more cost-effective investigations such as endoscopy are readily available.6 As non-invasive investigations, they would be better suited for investigation of primary IL in the paediatric cohort where invasive endoscopy is more distressing.2 Measurement of 24-hour faecal alpha-1-antitrypsin (A1AT) clearance is another reliable non-invasive investigation for diagnosing protein-losing enteropathy. Faecal A1AT clearance is typically elevated in protein-losing enteropathies, but might have limited use as a diagnostic aid specifically for primary IL.3
The main focus of treatment in primary IL has been dietary modifications and supplementation with diets high in protein and low in fat.1 MCT supplementation has also been shown to be beneficial in reducing malabsorption as these are absorbed directly into the portal circulation and bypass the lymphatic channels.1 For reasons that remain unknown, MCT supplements were not successful in our case, despite good compliance. Octreotide injections have shown to be effective in a number of articles.1 6 Regular use over 12 months in our patient did not result in any significant macroscopic remission of primary IL. However, it resulted in convincing and persisting clinical and biochemical improvement. It is not entirely clear how octreotide improves small bowel absorption in primary IL; it is thought to be related to its ability to inhibit absorption of triglycerides as well as its ability to induce temporary splanchnic vasoconstriction.3 Octreotide therapy may not have a place curing primary IL, but it has shown to be effective in relieving many of the symptoms and complications of malabsorption in primary IL where an MCT diet is unsuccessful or poorly tolerated.3 Other therapies that have been proposed for primary IL include corticosteroids and antiplasmin. However, data on their efficacy have so far been inconsistent.3
Surgical resection has shown to be a potentially curative intervention in a limited number of cases of primary IL where short segments of small bowel have been affected by the condition (≤20 cm).7 Cases requiring extensive small bowel resection would likely be complicated by short gut syndrome. Small bowel intestinal transplantation for cases of extensive IL is another potential treatment option that has not been considered yet, but there is currently no data or literature to support this as an intervention at present.
Learning points
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Primary intestinal lymphangiectasia (IL) is a rare condition characterised by impaired lymphatic circulation within the small bowel that ultimately results in malabsorption. Secondary causes of IL and/or protein-losing enteropathies (such as infections, systemic lupus erythematosus, malignancies) need to be excluded prior to confirming a diagnosis of primary IL.
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Diagnosis and evaluation of primary IL can be undertaken with either enteroscopy or capsule endoscopy. Periodic surveillance endoscopy should be performed in primary IL as patients are at risk of developing lymphoma as a complication. Currently, there is no established interval for surveillance endoscopy in IL.
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Successful treatment of the malabsorption associated with primary IL relies on the compliance to dietary modification consisting of a diet low in fat and high in protein content. Supplementation of the diet with medium-chain triglyceride (MCT) has shown to have added benefits in improving absorption and symptom relief.
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Our case establishes subcutaneous octreotide as an effective treatment in the management of primary IL that is refractory to dietary modifications and MCT supplements.
Acknowledgments
Histology images were kindly arranged and provided by Ms Jean Watson (Histopathology Office Manager) and Dr Anirudha Rajguru (Consultant Histopathologist) from the Histopathology Department at St Helier Hospital.
Footnotes
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Contributors AH is the primary author of the case report and has provided input into all sections of the case report. AH was involved in the care of the patient. PY is the patient’s consultant who has had overall responsibility for his investigations, diagnosis and treatment. They are also co-author on the report and have provided input in all sections of the case report. JT is a co-author and was the senior dietician involved in the patient’s care. They have provided input into the treatment of the condition. IH is a co-author on the report and has provided input into all sections of the case report.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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