Severe form of primary intestinal limphangiectasia in one year old child

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Severe form of primary intestinal limphangiectasia in one year old child

Bulegenova M., Mustafin O., Makhneva A., Bekisheva A.

Scientific center of pediatrics and children surgery, Almaty

Summary: Primary intestinal lymphangiectasia (Waldman syndrome) is congenital abnormality of the lymphatic system in children - a disease that occurs infrequently. There are about 80 published descriptions of this pathology in infants. The main clinical manifestation of intestinal lymphangiectasia is a syndrome of malabsorption: diarrhea, nausea, vomiting, abdominal pain, peripheral edema. In some cases, steatorrhea of varying severity occurs. Long lasting of the disease, no effect on the therapy leads to such complications as chylous ascites and chylothorax. This article presents a clinical case of an early debut primary intestinal lymphangiectasia in 6-month-old child, complicated by development of concomitant immunodeficiency. The final diagnosis was set after the histological examination of biopsy material in jejunum. Substitution therapy with albumin had no positive effect. Because of the constant hypoproteinemia that had not been corrected either albumin or ongoing corticosteroid therapy, it was decided to start the sandostatin therapy. With the improvement of patient condition, he was transferred from intensive care to the Department of somatic pathology. Transfusions of albumin have been cancelled. The protein level increased up to 53 g/l, swelling disappeared, but general sponginess of the tissue remained. Discharged from the hospital with recommendations to continue the combined therapy including sandostatin and compulsory monitoring the concentration of immunoglobulins.

Key words: intestinal lymphangiectasia, malabsorption syndrome, hypoproteinemia, immunodeficiency, sandostatin

Introduction: Primary intestinal lymphangiectasia (Waldman syndrome) is congenital abnormality of the lymphatic system in children - a disease that occurs infrequently. There are about 80 published description of this pathology in infants /1, 2/. Presumably, the basis for the development of this disease are genetic disorders, type of inheritance is an autosomal- recessive. However, in the available literature there are no data about the genetic mutations associated with the development of the indicated anomalies. The intestinal lymphangiectasiais is characterized by abnormal enlargement of the lymph vessels in the submucosal and mucosal layers of the colon. Pressure in the lymphatic system increases as a result of impaired lymph drainage and the lymph penetrates into the intestinal lumen /2,3/.Loss lymph, containing the main immune cells and immunoglobulins, contributes in emergence of secondary immunodeficiency, characterized by increased susceptibility to infectious diseases /4,5/.In addition, the process of intestinal absorption of fats, proteins and minerals disrupts, which leads to hypoproteinemia, hypolipidemia, hypocalcemia, often reduced content of iron and copper in the blood and malabsorption syndrome /3,6/.Primarily, loss of proteins is resulted in the essential decrease of proteins with a long half-life (albumin, ceruloplasmin, immunoglobulins M, G and A), while the concentration of proteins with short half-lives (immunoglobulin E, coagulation factors, prealbumin, transferrin) does not change significantly.If the usual consumption of albumin is 6-10% per day, albumin losses from intestinal enteropathy increase to 60%. Despite the ability of the liver to synthesize albumin, its activity is not enough to restore a normal level of protein /6, 7/.

The main clinical manifestation of intestinal lymphangiectasia is a syndrome of malabsorption: diarrhea, nausea, vomiting, abdominal pain, peripheral edema. In some cases, there is steatorrhea of varying severity. Persistent course, no effect on the therapy leads to such complications as chylous ascites and chylothorax.

In the treatment of the most severe cases of intestinal lymphangiectasia sandostatin is used. Sandostatin is a synthetic cyclic oktapeptid, derivative endogenous somatostatin with similar pharmacological effects and much longer effect duration. Somatostatin is synthesized by cells of the Central and peripheral nervous system, the hypothalamus, the islet cells of the pancreas (D-cells), glandular and neuronal cells of the stomach and intestines, acting as neurotransmitter /8,9/.It is also produced by inflammatory and immune cells, has autocrine, paracrine and endocrine effects. Somatostatin controls a large number of physiological functions: the transmission of nerve impulses, cell secretion and proliferation, muscular contractility, intestinal motility, nutrient absorption and function of the immune cells /10/. The effects of somatostatin are implemented through its interaction with specific somatostatin receptors (SSTR) /11/.

Sandostatin is an inhibitor of the endocrine and exocrine secretion of the pancreas, a modulator of intestinal motility, absorption of electrolytes and nutrients, secretion of the stomach and pancreas /8,12/. It reduces the arterial blood supply to the visceral organs and portal blood flow, inhibits pathologically increased secretion of growthhormone, as well as peptides and serotonin, produced in gastroenteropancreatic endocrine system. The injection of sandostatin is not accompanied by the phenomenon of hypersecretion of hormones by the mechanism of “negative feedback” [8, 12]. In patients sandostatin reduces vegetative-vascular reactions, apparently, is due to its effect on blood vessels and visceral blood flow [13]. Consequently, the hypovolemia associated with the loss of fluids through the intestines is reduced. The reduction of hypovolemia reduces the release of vasoactive substances (serotonin, histamine, catecholamines) that cause vegetative-vascular reactions.

Clinical observation:

Patient: B.A., 15.08.2014. In February 2015, at the age of 6 months was diagnosed with acute respiratory viral disease, accompanied by rise of temperature up to 38 °C. He was treated as outpatients, ampicillin was prescribed. For the first time mother noticed the swelling on the face, then, during breastfeeding atonic seizures with loss of consciousness occured. The child was hospitalized to the intensive care unit of the regional children's hospital in Aktau. The severity of the condition when taken to the hospital due to neurological symptoms. Biochemical analysis: hypocalcemia(1.57 mmol/l) and hypoproteinemia (31 g/l) was detected. Blood tests for CMV (ELISA, PCR) were negative. Ultrasound of abdominal organs: the presence of a small amount of perihepatic effusion, in and around the splenic departments, between loops of bowel. Computer tomography of the brain revealed retrocerebellar cyst. The disease was complicated by bronchopneumonia. The patient was prescribed antibacterial and symptomatic therapy with positive dynamics. With the improvement of the health status the child was discharged, however, the concentration of protein in the blood remained at a low level (up to 35 g/l). Diagnosis at discharge: pneumonia (severe), retrocerebellar cyst, seizures caused by hypocalcemia. Idiopathic nephrotic syndrome.

However, 2 weeks after discharge, swelling in the face and extremities appeared again, because of what the child was sent to the Scientific Center of Pediatrics for further diagnosis. Health status at admission was of moderate severity. The skin was without rashes, skin turgor decreased, edema of the lower extremities. In the biochemical analysis of blood: protein concentration in serum - 28.0 g/l, albumin 24 g/l, CRP - 9.0 mg/l (followed by a significant increase to 292.4 mg/l within 2 days), hypocalcemia (1.99 mmol/l). Analysis on protein fractions showed decrease of albumin (50% of the reference), б1-globulins - within normal limits, б2 -globulins -was decreased by 50% from the norm, в1-globulins reduced by 28%, в2-globulins - a decline of 80 %, y- globulins reduced by 98% from normal content.

Clinical signs: the temperature rose up to 38 0C, restlessness, single vomiting, bloating.

Esophagogastroduodenoscopy study: mucosa of the duodenum and jejunum- moderate edematous, thick white coating was observed on the walls of the intestine. lymphangiectasia malabsorption hematoxylin eosin

Histological examination of the jejunum biopsy: Examination of the biopsy of the jejunim mucosa revealed that brush border is visualized throughout. Villi of varying heights, the accumulation of net eosinophilic masses visualized, consolidate friable surface epithelium with the formation of cystic cavities, deforming the villi. Dilated lymphatic vessels were also revealed (Fig 1,2). Crypts are not changed, the number of goblet cells within norm. Panett cells had a moderate amount of azurophilic granules. Lymphoplasmocytic infiltration were revealed in stroma. Conclusion: intestinal lymphangiectasia. Chronic atrophic eyunit without exacerbation.

The results of immunological examination: the total number of leucocytes within norm, absolute lymphopenia. The ratio of cell subpopulations was severely disrupted due to the decrease of the absolute number of T-helper lymphocytes. The content of activated T- and B-lymphocytes increased. Severe hypogammaglobulinemia of all classes. Immunologist opinion: concomitant immunodeficiency manifested by infectious syndrome due to the underlying disease.

The doctors, taking into account the age of the infant patient, the presence of massive, symmetrical, peripheral edema, absence of factors that trigger the occurrence of secondary lymphangiectasia, as well as basing on data of histological examination, put the final diagnosis of primary intestinal lymphangiectasia syndrome (Waldman), secondary immunodeficiency.

Treatment at the initial stage of therapy was as follows: transfusion of albumin to restore protein levels, antibacterial drugs to prevent infectious processes, Octagam to restore the concentration of antibodies, prednisone for anti-inflammatory, as well as drugs for the correction of electrolyte disturbances. Positive effect detected, the child's condition had remained moderate severity without deterioration. The concentration of serum protein after albumin transfusions increased up to 40-42 g/l for a short period of time. Because of the constant hypoproteinemia which was not corrected by albumin and ongoing corticosteroid therapy, decision to start sandostatin therapy in the dosage of 1 mg/kg was made.

Cyanosis of the extremities and restlessness appeared 2 hours after injection, but these side effects were leveled in the next hour. Biochemical analysis showed the increase of the protein level up to 46 g/l. With the improvement of the health status child was transferred from intensive care to the Department of somatic pathology. Two days after therapy with sandostatin transfusions of albumin were cancelled. During treatment the protein level increased up to 53 g/l, swelling disappeared, but general sponginess of the tissue still remained. The patient was discharged with recommendations for the permament sandostatin therapy and compulsory monitoring of immunoglobulin level.

Discussion:

- Intestinal lymphangiectasia should be suspected in every patient with obscure symptoms of hypoalbuminemia, especially on the background of steatorrhea and/or lymphocytopenia.

- Thus, this clinical case has the following interesting features:

1. a rare occurrence pathology

2. uncommon early onset

3. the severity of developed immunodeficiency,

4. manifested infectious syndrome that made difficult to diagnose the underlying disease

5. rare use of sandostatin in children the first year of life

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