Curr Pediatr Res 2016; 20 (1&2): 268-272
ISSN 0971-9032
www.currentpediatrics.com
A case of gastric rupture in non-neonatal child with incontinentia pigmenti and
intestinal neuronal dysplasia, is there any correlation?
Ester De Luca1, Debora De Bartolo1, Natalia Minelli2, Francesco Ausania1, Santo Gratteri1, Pietrantonio
Ricci1
1
Institute of Legal Medicine, University “Magna Graecia” of Catanzaro, Italy, 88100 Germaneto
Institute of Legal Medicine, Catholic University of Sacred Heart, Italy, 00168 Roma
2
Abstract
Gastric rupture is extremely rare in childhood beyond the neonatal period and the etiology
of this condition in preschool children remains obscure. We report a case of 6 year old
girl who sustained sudden and lethal gastric rupture. The young patient was affected by
Incontinentia Pigmenti (IP), a genetic disease; she had an episode of nausea and vomiting
the day before admission to the emergency ward. Abdominal X-ray showed free air in the
abdominal cavity, an emergency laparotomy detected a wide perforation of posterior gastric
wall. The post-operative course was complicated by a cardiac arrest and an autopsy was
performed. Histological examination showed ulcerations and erosions in gastric mucosa
with thrombosis in the blood vessel in the submucosa and it suggested Intestinal Neuronal
Dysplasia (IND) type B. An eventual correlation between the three diseases that affected our
patient was investigated. After a review of literature we have found that the presence of IP
not appears to be associated with the other two diseases; so, in our case, it can be considered
as a pre-existing pathology. About IND, even if it was never described any case in which this
condition has determined gastric rupture, we think, on the basis of clinical and histological
findings, that it has determined an increase of pressure at gastrointestinal level, with serious
stomach distension until fatal gastric rupture.
Keywords: Gastric rupture, Childhood, Incontinentia pigmenti, Intestinal neuronal dysplasia, Autopsy.
Accepted October 20, 2016
Introduction
compression of the aorta and mesenteric vasculature [4,5].
Spontaneous rupture of stomach sometimes occurs in the
neonatal period but it is rarely seen beyond the neonatal
period; currently the etiology of this condition in preschool
children remains obscure [1]. All articles on spontaneous
idiopathic gastric rupture in pre-school age children have
only been reported in Japanese and Chinese literature and
there are isolated European cases [2,3]. These cases showed
several common features. The clinical manifestations
include severe abdominal pain, distension, vomiting and
respiratory distress and they progress rapidly with high
rate of mortality.
About pulmonary effects, it’s important to stress the role
of the diaphragm to balance pressure between thoracic and
abdominal cavities [6]. In cases of gastric rupture TP can
determinate diaphragm elevation and respiratory failure [4].
From a pathophysiological point of view gastric rupture
can cause a Tension Pneumoperitoneum (TP), than
develops as air is trapped within the peritoneal cavity and
cannot escape.
The trapped air is under tension leading to rising
intraperitoneal pressure, this condition can determinate
cardiovascular effects as decrease of venous return through
the inferior vena cava, with cardiac output reduction;
268
Incontinentia Pigmenti (IP) also known as BlochSulzberger syndrome, is a rare X-linked dominant
inherited genodermatosis, usually lethal in males even in
the prenatal period [4,7]. IP is caused by mutations in the
NEMO gene (IKK-gamma), located in Xq28 locus.
IP is considered to be a syndrome of multisystem
polydysplasias; it affects ectodermal and mesodermal
tissues, such as skin, eyes, teeth and central nervous system.
There are around 800 registered cases worldwide and the
estimated incidence is about 1 to every 40.000 children.
The estimated prevalence of IP was stated to be 0.2 in
100,000 based on the data available literature published
during the period of 2000–2013 [5,8]. Infant mortality is
associated with bacterial infection, and malfunction of the
central nervous system [6,9].
Curr Pediatr Res 2016 Volume 20 Issue 1 & 2
A case of gastric rupture in non-neonatal child with incontinentia pigmenti and intestinal neuronal dysplasia, is there any correlation?
Intestinal Neuronal Dysplasia (IND) is a clinical condition
characterized by a malformation of enteric plexus. It
was first described by Meier-Ruge in 1971 [7,10] and, in
1983, Fadda et al. sub classified it into two clinically and
histologically distinct subtypes [8,11]. Type A occurs in
less than 5% of cases and is characterized by congenital
aplasia or hypoplasia of the sympathetic innervations; it
presents acutely in the neonatal period with episodes of
intestinal obstruction, diarrhea and bloody stools. Type
B (95% of cases) is characterized by malformation of the
parasympathetic of submucous and myenteric plexuses
with hyperganglionosis [9,12].
The incidence of this disease is of approximately 1 in every
7,500 newborns, but there is a great variability in frequency
of isolated IND between different countries, with reported
rates between 0.3 and 40% of all rectal suction biopsies
[10-15]. About pathogenesis there is no consensus, in
fact it is unclear whether IND is due to primary factors
such as gene abnormalities, or secondary changes due
to enterocolitis and constipation [13,14,16,17]. From a
clinical point of view, patients with IND Type B present
with intractable constipation and grossly slowed intestinal
transit time. In particular, it may occur alone or associated
with other neuropathies, such as Hirschsprung’s disease,
but clinical features are variable and children can show
different degrees of chronic constipation ranging from
slight constipation to severe cases with abdominal
distension and vomiting [15-20].
cardiac arrest that was treated by successful resuscitation.
The gastric lesion was sutured. However, the postoperative course was complicated by a new fatal cardiac
arrest.
An autopsy was performed and tissue samples were taken
for subsequent histological examination.
Macroscopically we have found: signs of gastric
perforation with suture stitches; hemorrhagic effusion
in gastric cavity and pouch of Douglas; many gastric
ulcerations (Figure 2); decreased bowel wall thickness
and alternation of dilated and partial obstructed sections;
atrophy of the cerebral cortex; signs of acute respiratory
distress and left ventricular hypertrophy.
We report a case of child affect by Incontinentia Pigmenti,
who presented a lethal gastric rupture with a histological
suspect of Intestinal neuronal dysplasia type B.
Case Report
A 6 year old girl was admitted to pediatric department
because of lethargy, nausea, vomiting, crying spells and
general discomfort the day before admission. No history
of trauma was reported. Her past clinical history was
characterized by diagnose of Incontinentia Pigmenti
when she was 12 month old (spastic tetraparesis,
mental retardation, speech/language delays, nystagmus
and alteration of visual evoked potentials -VEP). On
examination, she was listless, dehydrated and the
abdomen was progressively becoming distended and
tensed. Laboratory examination showed leukocytosis
(WBC 18.620/mmc), hyperglycemia and an increase of
amylase (221 U/L). By nasogastric tube gas with digested
blood material flowed. Abdominal X-ray showed free air
in the abdominal cavity (Figure 1), dilated bowel loops,
fecal impaction and colonic interposition between the
liver and diaphragm. There was uncertainty about the
diagnosis because of the unusual presentation, with a
delay in the transfer to a pediatric surgery unit. The child’s
general condition deteriorated rapidly: comatose state,
acute abdomen with hernia of umbilicus and rectum. A
transverse supra-umbilical laparotomy was performed, the
peritoneal cavity was filled with cloudy and brownish fluid
and a perforation at the posterior wall of the stomach was
detected. The intra-operative course was complicated by a
Curr Pediatr Res 2016 Volume 20 Issue 1 & 2
Figure 1. Abdominal X-ray showed free air in the
abdominal cavity
Figure 2. Macroscopic examination of gastric mucosa:
gastric ulcerations and hyperemia areas (arrows)
269
De Luca/De Bartolo/Minelli/Ausania/Gratteri/et al.
Histological examination showed ulcerations and erosions
in gastric mucosa with thrombosis in the blood vessel in
the submucosa. The muscle layer of the colon showed
areas of unequal thickness and the tunica submucosa
showed areas of sclerosis and abundance of lymphatic
nodules. Furthermore, tissue samples were characterized
by accumulations of giant ganglia (>10 unit) in thickened
bowel segments. They were observed segments of the
colon where the muscle layer is thinned and at this level it
was seen reduction or absence of neuronal elements. Also
the small intestine tissue samples showed accumulations
of neuronal elements.
Discussion
The case that we have reported presents three different
diseases: gastric rupture, incontinentia pigmenti and IND;
so it is characterized by pathologies that have not a known
association in literature.
Nevertheless, we think that, in the present case, gastric
rupture occurred because of a synergic action between
gastric lesions and vomiting IND-induced, instead
the presence of IP can be considered as a pre-existing
pathology that does not appear to be associated with the
other two diseases.
Rupture of a normal stomach occurs because of increased
intragastric pressure until the tensile strength of the
stomach wall is exceeded. The gastric wall becomes
large and thin and its blood vessels becomes extended,
constricted and even obstructed, resulting in ischemia
[18,19,21,22]. It has also been reported that increase of
the intra-abdominal pressure after labored coughing
or vomiting, blunt abdominal trauma, ulcers, tumours,
cardiopulmonary resuscitation and the Heimlich maneuver
can precipitate rupture [1,19,20,22,23].
In this case, there was no history of trauma or any other
underlying diseases.
The literature search suggests that perforation along
the lesser curve, such as in this case, is usually due to a
distended stomach [21,24].
The patient of our case presented, at post mortem
histological examination, ulcerations and erosions in
gastric mucosa with thrombosis in the blood vessel of
submucosa.
From the other hand, the same examination showed areas
of unequal thickness in the muscle layer of the colon and
areas of sclerosis and abundance of lymphatic nodules of
the tunica submucosa. Furthermore, tissue samples were
characterized by accumulations of giant ganglia (>10
units) in thickened bowel segments of both colon and
small intestine.
On the basis of these findings, we have suspected a
diagnosis of IND type B.
In literature there is lack of consensus in diagnostic
criteria of IND; initially diagnosis was based on AChE
histochemistry of nerve fibers in rectal suction biopsies
[22,25]. However the AChE activity in the lamina
270
propria mucosae has been shown to be an age-dependent
phenomenon that disappears on maturation of the
submucosal plexus; so, at present, the most commonly
used diagnostic criteria are: (1) more than 20% of 25
submucosal ganglia must be giant ganglia containing 9
or more ganglion cells and (2) the patient must be older
than 1 year, as before that age, giant ganglia may be
misinterpreted due to the fact that immature ganglia often
have an incomplete differentiation in nerve cells [23-29].
In addition to histology, IND diagnosis is coherent with
clinical presentation of our little patient. In fact IND
usually presents with intractable constipation and grossly
slowed intestinal transit time, even if clinical features
are variable and children can show different degrees of
chronic constipation ranging from slight constipation to
severe cases with abdominal distension and vomiting
[16,17,19,20]. About IP, we do not know what the role of
this pathology was in the presented case.
Clinically IP is characterized by cutaneous findings,
classically subdivided into four stages: vesiculobullous,
verrucous, hyperpigmented, and atrophic [27,28,30,31].
Stage 1, known as inflammatory or vesiculobullous
stage, is characterized by the development of papules,
vesicles and pustules on an erythematous base, this
phase can be confused with herpes simplex, varicella or
impetigo [29,32]. The vesicular stage occurs in 90-95%
of patients. In most patients (>90%) lesions are present
at birth or develop during the first two weeks of life and
then disappear by 4 months of age [30,33]. The skin
lesions generally regress spontaneously [31,34]. The hair
may also be affected in IP: scarring alopecia, usually on
the vertex, is the most common manifestation of hair
involvement, in addition, the hair can be sparse in infancy
and later have a dull appearance and brittleness [32,35].
Although ocular manifestations in Incontinentia pigmenti
Syndrome are not the most common (with a frequency
of 35 to 77% on the studied populations), they are often
highly debilitating [33,34,36,37]. Ocular abnormalities
are typically divided into retinal (foveal hypoplasia,
anomaly of retinal pigment epithelium, retinal vascular
non-perfusion, neovascularization, vitreous hemorrhage
and retinal detachment) and nonretinal manifestations
(strabismus, nystagmus, optic nerve atrophy, conjunctival
pigmentation, iris hypoplasia and uveitis) [33,3540]. The central nervous system disorders in patients
with IP can have a major impact on quality of life. In
the literature, neurological manifestations have been
reported approximately in 18 to 36% of cases forming
one of the major causes of morbidity and mortality of the
condition [38,39,41,42]. Seizures, delayed psychomotor
development, hemiplegia, hemiparesis, microcephaly,
Neuronal heterotopias (normal neurons found in abnormal
locations), spasticity, cerebral atrophy and mental
retardation are the major reported neurological findings
[28,31,32,35,40,43].
It was not found any association between IP and gastric
lesions/rupture or between IP and IND, except for a
single case in which it was observed incontinentia
Curr Pediatr Res 2016 Volume 20 Issue 1 & 2
A case of gastric rupture in non-neonatal child with incontinentia pigmenti and intestinal neuronal dysplasia, is there any correlation?
pigmenti and segmental dilation of colon, even if as
isolated event [41,44]. About IND, it can be associated to
various gastrointestinal and not gastrointestinal diseases,
such as anorectal malformations, intestinal malrotation,
congenital short small bowel, hypertrophic pyloric
stenosis, necrotizing enterocolitis, intestinal atresia,
diffuse intestinal angiomatosis, microvillus agenesia,
vesical dysfunction and megacystis, mental retardation,
short stature, facial dysmorphia, Down’s syndrome,
histiocytosis, hearing loss [42,45]. In our knowledge, it
was never described any case in which IND has determined
gastric rupture. Nevertheless, on the basis of clinical and
histological findings, we have hypothesized that IND has
determined an increase of pressure at gastrointestinal level,
with serious stomach distension. Therefore, in our opinion
ulcerations and erosions of the gastric wall predisposed
this patient to gastric rupture during vomiting. What was
the role of IP in the pathophysiological sequence above
described is uncertain, so, at present, we don’t know if
the association between IP and IND can be considered as
isolated event, as previously reported in literature, or not.
We hope further investigations can solve these questions.
7. Smahi A, Courtois G, Vabres P, et al. Genomic
rearrangement in NEMO impairs NF kappa B activation
and is a cause of incontinentia pigmenti. The International
Incontinentia Pigmenti (IP) Consortium Nature 2000;
405: 466-472.
Conclusion
13. Granero Cendón R, Millan Lopez A, Moya Jimenez MJ,
et al. Intestinal neuronal dysplasia: Association with
digestive malformations. Cir Pediatr 2007; 20: 166–168.
Gastric rupture in children, although rare, is rapidly
progressive with high mortality and can be easily
misdiagnosed. Early diagnosis and treatment, with a clear
knowledge of possible favoring conditions will reduce
complications and mortality. The pathological findings
provide us some insights to consider the pathogenesis of
gastric rupture in childhood.
Finally, we recommend autopsy and histological analysis
to identify possible associations between rare pathologies,
such as IND and gastric rupture of our case. In fact, we
think that knowledge of these associations could avoid
dangerous delay in treatment.
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Correspondence to:
Ester De Luca,
Institute of Legal Medicine,
University “Magna Graecia” of Catanzaro, Germaneto,
88100, Italy.
Tel: +39 3208556232
E-mail: delucaester@gmail.com
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Curr Pediatr Res 2016 Volume 20 Issue 1 & 2