Paediatrics and International Child Health

ISSN: 2046-9047 (Print) 2046-9055 (Online) Journal homepage: http://www.tandfonline.com/loi/ypch20

Protein-losing enteropathy in an infant with

rotavirus infection

Adriana Parisi, Alessandro Cafarotti, Roberta Salvatore, Piernicola Pelliccia,

Luciana Breda & Francesco Chiarelli

To cite this article: Adriana Parisi, Alessandro Cafarotti, Roberta Salvatore, Piernicola Pelliccia,
Luciana Breda & Francesco Chiarelli (2017): Protein-losing enteropathy in an infant with rotavirus
infection, Paediatrics and International Child Health, DOI: 10.1080/20469047.2017.1295011

To link to this article: http://dx.doi.org/10.1080/20469047.2017.1295011

Published online: 06 Mar 2017.

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Paediatrics and International Child Health, 2017
http://dx.doi.org/10.1080/20469047.2017.1295011

Protein-losing enteropathy in an infant with rotavirus infection

Adriana Parisi, Alessandro Cafarotti, Roberta Salvatore, Piernicola Pelliccia, Luciana Breda and
Francesco Chiarelli
Department of Paediatrics, University of Chieti, Chieti, Italy

ABSTRACT ARTICLE HISTORY

Protein-losing enteropathy (PLE) is a rare gastro-intestinal complication characterised by Received 1 March 2016
intestinal loss of proteins with consequent hypoproteinaemia and generalised oedema. Rotavirus Accepted 9 February 2017
infection associated with PLE in children has rarely been reported. A 6-month-old girl presented KEYWORDS
with diarrhoea, fever and generalised oedema. Total serum proteins were 34 g/L (61–79) and Rotavirus; protein-losing
plasma albumin 16.8 g/L (40–50), serum sodium was 126 mmol/L and there was mild metabolic enteropathy; child; oedema
alkalosis (pH 7.46). Stool for alpha-1 antitrypsin was  >1.2  mg/g (<0.6) which supported the
diagnosis of PLE. Stool examination demonstrated the presence of rotavirus antigen by the rapid
immunochromatographic test. Abdominal ultrasound showed bowel distension and intestinal
wall thickening with a small amount of ascites. Echocardiography excluded pericardial effusion.
Two albumin infusions (1 g/kg) were required to sustain normal serum albumin levels. Over the
next 2 weeks, there was gradual normalisation of stools and progressive reduction of oedema.
In children with acute and symptomatic PLE, rotavirus should be considered in the differential
diagnosis. The availability of the rapid immunochromatographic test facilitates the diagnosis. In
most cases, supportive care alone is sufficient, but albumin infusions may be required in more
severely affected children.

Introduction
Protein-losing enteropathy (PLE) is a clinical entity char-
acterised by abnormal protein loss from the digestive
tract, resulting in decreased serum proteins with associ-
ated hypogammaglobulinaemia and lymphocytopenia
[1]. Consequently, oedema, ascites and pleural and car-
diac effusions may occur.
In children, PLE is caused by intestinal metabolic and
inflammatory disorders, lymphatic obstruction, or infec-
tious disease. The Fontan procedure is also associated
with this complication [2,3].
Rotavirus (RV) is the most common cause of diar-
rhoea in young children. It typically affects infants,
causing vomiting, watery diarrhoea and low-grade
fever. Morbidity and mortality are linked to RV-induced
complications such as central nervous system (CNS)
involvement, severe dehydratation with shock and dis-
seminated intravascular coagulation (DIC) [4].
A 6-month-old girl with PLE and rotavirus infection
is presented.
Case report
A 6-month-old girl presented to the Department of
Paediatrics, University of Chieti, Chieti with a 1-week
history of diarrhoea (3–4 times per day), lack of appe-
tite and fever of c. 38°C. The family’s medical history
was normal. She had been born by caesarean section
at 38  weeks gestation following a normal pregnancy,
no prenatal disorder had been reported and her birth
weight was 3.6 kg. The neonatal period was uneventful.
She was exclusively breastfed, had been gaining weight
consistently and was on the 25th percentile. She received
the mandatory vaccinations but not for rotavirus. In the
first months of life she had been in good health.
At home the child had been given oral rehydration
solutions containing a balanced blend of minerals and
glucose; however, the day before admission, her clini-
cal condition deteriorated and generalised oedema
was observed. On examination, her weight was 6.7 kg
(25th–50th percentile), the anterior fontanelle was
depressed, and there was peri-orbital pedal and pre-tibial
pitting oedema, abdominal distension and hypo-active
bowel sounds; there was no clinically apparent ascites.
No blood was detected in the stools.
Temperature was 37.5°C, blood pressure was
90/60 mmHg, heart rate 132 beats/min and respiratory
rate 28 breaths/min.
Investigations. Total proteins were 34  g/L (61–79)
and plasma albumin 16.8  g/L (40–50). Serum sodium

CONTACT  Adriana Parisi  adrianaparisi@virgilio.it

© 2017 Informa UK Limited, trading as Taylor & Francis Group
2   A. PARISI ET AL.

Table 1. Clinical characteristics and treatment of four infants with PLE associated with RV infections.
Age at presentation Symptoms Mean disease duration, days Therapy
Bharwani et al. [4] 10 months Vomiting 12 Correction of fluid and electrolyte imbalance
Diarrhoea
Fever IV albumin
Seizures Antibiotics
Dyspnoea FFP and PRBC transfusions
Parenteral nutrition
Iwasa et al. [5] 6 months Vomiting >5 Parenteral nutrition
Diarrhoea IV albumin
IV gamma globulin
Corticosteroids
Aldemir-Kocabaş 8 months Vomiting 12 Correction of fluid and electrolyte imbalance
et al. [6] Diarrhoea
Fever Corticosteroids
Antibiotic
Present case 6 months Diarrhoea 15 Correction of fluid and electrolyte imbalance
Lack of appetite
Fever IV albumin
Note: IV, intravenous; FFP, fresh frozen plasma; PRBC, packed red blood cells.

Table 2. Causes of protein-losing enteropathy (adapted from Pediatrics [10]).

Abnormality of the lymphatic system
(i) Primary intestinal lymphangiectasia
(ii) Secondary lymphangiectasia Crohn disease
Ulcerative colitis
Sarcoidosis
Lymphoma
Fontan procedure
Increased lymphatic pressure Constrictive pericarditis
Congestive heart failure
Congenital heart disease
Genetic syndromes Noonan
Turner
Mucosal injury
(i) Enteric infections Salmonella
Shigella
Giardia lamblia
Rotavirus
Cytomegalovirus
Campylobacter
Clostridium difficile
(ii) Auto-immune and inflammatory disorders Crohn disease
Ulcerative colitis
Eosinophilic gastro-enteritis
Coeliac disease
Tropical sprue
Systemic lupus erytematosus
Henoch-Schönlein purpura
(iii) Others Ménétrier’s disease
Kaposi’s sarcoma
Adenocarcinomas

was 126 mmol/L and potassium 4.7 mmol/L, and there
was mild metabolic alkalosis (pH 7.46). The white blood
cell count was 10.9 × 109/L, with 79% lymphocytes and
3.7% neutrophils, and the platelet count was 469 × 109/L.
Haemoglobin was 11.3 g/dL and haematocrit was 34.8%.
C-reactive protein, renal, liver and thyroid function tests
were normal. Serum immunoglobulin IgG was 1.5  g/L
(1.72–10.69), IgM 0.30 g/L (0.33–1.26) and IgA 0.027 g/L
(0.04–0.84). Urinalysis was normal including negative
protein. Serology was negative for Epstein–Barr virus,
cytomegalovirus and adenovirus. Stool culture was
negative for bacteria and fungi; Giardia lamblia antigen
and occult blood tests were negative. Stool for alpha-1
antitrypsin was > 1.2 mg/g (<0.6), supporting PLE. Stool
examination by the rapid immunochromatographic test
demonstrated the presence of rotavirus antigen.

Abdominal ultrasound demonstrated bowel expan-
sion and thickening of the wall of the small intestine,
with mild ascites. Electrocardiogram showed sinus tach-
ycardia and echocardiography was normal, excluding
pericardial effusion.
An infusion of intravenous albumin (1  g/kg) was
administered, followed by a continuous infusion of a
glucose and electrolyte solution; after 48 h, however, a
second albumin infusion (1 g/kg) was required to main-
tain serum albumin levels. After each albumin infusion,
furosemide (1 mg/kg) was given to avoid massive fluid
shift into the intravascular compartment. Oral feeding
was reintroduced gradually and over the next 2 weeks
there was normalisation of stools and progressive reduc-
tion of oedema. Two weeks after admission, the infant
was discharged in a good clinical condition. At follow-up
1 week later, she weighed 6.3 kg (10th–25th percentile)
and was back to normal health with a good appetite; the
ascites and oedema had resolved and albumin, sodium
and immunoglobulin were within normal ranges. Repeat
rapid stool test for rotavirus was negative.
Discussion
Rotavirus (RV), the most common cause of severe diar-
rhoea among infants and young children worldwide, has
rarely been reported to be associated with PLE (Table 1)
[4–6].
PLE may complicate various auto-immune disorders,
neoplasms, infections and abnormalities of the lym-
phatic system such as primary intestinal lymphangiec-
tasia, congestive heart failure and the Fontan procedure
[7]. Salmonella, shigella, Giardia lamblia, campylobacter,
Clostridium difficile and cytomegalovirus are the most
common causative agents [8] (Table 2).
The pathophysiology of PLE associated with RV is
probably owing to intestinal mucosal injury followed by
enhanced permeability and subsequent protein leakage
into the gut lumen.
A summary of four cases including this one is pre-
sented in Table 1. In all four reports, the infants were
under 1  year of age; the mean duration of gastro-
intestinal symptoms before the appearance of oedema
ranged from 3 to 7  days and the mean duration of
disease from 12 to 15  days. Case 1 presented with an
aggressive systemic inflammatory reaction with seizures,
anasarca and hypovolaemic shock and required intensive
care. Cases 2 and 3 received intravenous corticosteroids
with rapid improvement of symptoms; the outcome was
favourable in all four infants with complete resolution of
symptoms and no sequelae [5,6].
The mechanism by which RV affects the intestinal
mucosa is not fully understood. It is well known that
RV infects mature enterocytes at the top of the villi of
the small intestine of mammalian species, where there
PAEDIATRICS AND INTERNATIONAL CHILD HEALTH   3
is vacuolisation and epithelial loss of cells, followed by
crypt hyperplasia. Rotavirus causes destruction of the
epithelium, villous ischaemia, through the action of
NSP4, a viral enterotoxin, and activation of the enteric
nervous system, resulting in malabsorption [9]. It has also
been shown that in immunocompromised hosts RV can
replicate in the liver and biliary system and cause biliary
atresia and pancreatitis [9]. In most cases, PLE is diag-
nosed by the history, physical examination and clinical
manifestations. However, a decrease in alpha-1-antit-
rypsin concentration is a useful indicator of gut damage,
as in this case [7].
PLE treatment options include maintenance of nutri-
tional status and treatment of the underlying disease.
In all patients with PLE, a high-protein diet is usually
recommended; in the most severe cases albumin infu-
sions might be necessary, as in this case. Our patient’s
clinical symptoms improved slowly and she required
two albumin infusions. However, albumin infusions are
effective only in the short-term as a bridging interven-
tion [7]. The use of corticosteroids is controversial; some
authors report the beneficial effects of oral budesonide
in selected patients with PLE after the Fontan procedure
[2,3].
In conclusion, PLE is a rare complication of various
diseases in children and it is characterised by loss of
­proteins into the gastro-intestinal tract. Stool alpha-1
anti-trypsin clearance is a useful tool to aid diagnosis
of PLE. Rotavirus should be considered in children, par-
ticularly infants, with acute and symptomatic PLE. The
availability of the rapid immunochromatographic test
facilitates the diagnosis. Supportive care is usually suf-
ficient, but albumin infusions may be required in more
severely affected patients.
Disclosure statement
No potential conflict of interest was reported by the authors.
Notes on contributors
Adriana Parisi is a resident in Paediatrics and she works in
the Department of Paediatric of Chieti University. In particu-
lar, she handles paediatric nephrology and cooperates in
the management of paediatric nephrology and paediatric
ultrasound outpatients' department. Her research interests
include paediatric nephrology, ultrasound and general pae-
diatrics. She has recently collaborated in a research studying
kidney function in children with juvenile rheumatoid arthritis
and she plans to study kidney function in obese outpatient
children.
Alessandro Cafarotti is a pediatrician, specialized in the
Department of Paediatric of Chieti University in 2016.
Currently, he works in his general paediatrics medical office
and performs paediatric ultrasounds. The author’s recent
publications have appeared in Pediatr Ann (2014), Ultraschall
Med (2011) and Eur J Pediatr (2011).
4   A. PARISI ET AL.
Roberta Salvatore is a resident in Paediatrics and she works
in Department of Paediatric of Chieti University. In particular,
she handles paediatric nephrology and general paediatrics.
Her research interests include paediatric nephrology and
general paediatrics. The author’s recent publications have
appeared in Pediatr Ann (2014) and Eur J Pediatr (2011).
Piernicola Pelliccia is a medical doctor of the Paediatric
Department of Chieti and he is responsible of paediatric
nephrology and ultrasound outpatients' clinic of that depart-
ment. His research interests include paediatric nephrology,
ultrasound and general paediatrics. The author’s recent publi-
cations have appeared in Pediatr. Ann. (2014), Pediatr Radiol.
(2012), Pediatr Nephrol. (2011), Ultraschall Med (2011) and Eur
J Pediatr (2011).
Luciana Breda is a medical doctor of the Paediatric Department
of Chieti and she is responsible of paediatric rheumatology
outpatients' clinic of that department. Her research interests
include general paediatrics and, above all, paediatric rheuma-
tology. The author’s recent publications on related issues have
appeared in the Lancet (2017), Pediatr Rheumatol Online J.
(2016), Ital J Pediatr. (2016) and J Pediatr. (2016).
Francesco Chiarelli is full professor of paediatrics of Chieti
University. He has particular interest in paediatric endocri-
nology and deals mainly of children with poor growth. His
research interests include all aspects of paediatrics, in par-
ticular paediatric endocrinology. The author’s recent publica-
tions on related issues have appeared in Acta Paediatr. (2017),
Mol Cell Endocrinol. (2017), Pediatr Diabetes. (2016), J Pediatr
Endocrinol Metab. (2016) and many others.
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