Pyloric Atresia Associated with Epidermolysis Bullosa: A Report of 4 Survivals in 5 Cases

Abstract

Objective: Pyloric atresia (PA) is a rare congenital anomaly that constitutes approximately 1% of allintestinal atresias, and its incidence is approximately 1 in 100,000 live births. PA may occur as anisolated condition or associated with other abnormalities, the most common being Junctionalepidermolysis bullosa (EB). Evidence suggests that PA-EB is a distinct entity. In this report, wepresent 5 cases of pyloric atresia associated with Junctional epidermolysis bullosa, 4 of whomsurvived after surgery.Cases Presentation: Prospective evaluation of 5 patients with pyloric atresia associated withEpidermolysis bullosa undergoing therapeutic surgery. Biopsy of the fresh bulla was compatible withJunctional EB in all 5 patients. All patients underwent laparatomy after stabilization. Four neonatesunderwent gastroduodenostomy, and one patient had excision of membrane and pyloroplasty. Out of5 neonates, 4 survive and one died from fulminant septicemia 12 days after operation.Conclusion: Although association of PA with EB has been reported to be fatal, recently there havebeen encouraging reports of survival among these patients. These 5 patients underwent surgery andsurvived, and are doing well on follow up.

Full text

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* Correspondence author;
Address: Department of Pediateric Surgery, Booali Sina Hospital, Sari, Iran. P.O. Box: 4715838477
E-mail: alireza_alam@yahoo.com


Pyloric Atresia Associated with Epidermolysis Bullosa:
A Report of 4 Survivals in 5 Cases
Alireza Alam-Sahebpoor*1, MD; Vajihe Ghaffari2, MD; Leila Shokoohi3, MD
1. Pediatric Surgeon, Department of Pediatric Surgery, Mazandaran University of Medical Sciences, IR
Iran
2. Neonatologist, Department of Pediatrics, Mazandaran University of Medical Sciences, IR Iran
3. Fellowship of Pediatric Surgery, Mazandaran University of Medical Sciences, IR, Iran
Received: 23/07/06; Revised: 16/10/06; Accepted: 28/12/06
Abstract
Objective: Pyloric atresia (PA) is a rare congenital anomaly that constitutes approximately 1% of all
intestinal atresias, and its incidence is approximately 1 in 100,000 live births. PA may occur as an
isolated condition or associated with other abnormalities, the most common being Junctional
epidermolysis bullosa (EB). Evidence suggests that PA-EB is a distinct entity. In this report, we
present 5 cases of pyloric atresia associated with Junctional epidermolysis bullosa, 4 of whom
survived after surgery.
Cases Presentation: Prospective evaluation of 5 patients with pyloric atresia associated with
Epidermolysis bullosa undergoing therapeutic surgery. Biopsy of the fresh bulla was compatible with
Junctional EB in all 5 patients. All patients underwent laparatomy after stabilization. Four neonates
underwent gastroduodenostomy, and one patient had excision of membrane and pyloroplasty. Out of
5 neonates, 4 survive and one died from fulminant septicemia 12 days after operation.
Conclusion: Although association of PA with EB has been reported to be fatal, recently there have
been encouraging reports of survival among these patients. These 5 patients underwent surgery and
survived, and are doing well on follow up.
Key Words: Pyloric atresia, Epidermolysis bullosa, Gastroduodenostomy, Surgery
Introduction
Pyloric atresia (PA) is a rare malformation which
is estimated to be responsible for less than 1% of
gastrointestinal atresias with an incidence of 1 in
100,000 live births.[1] Anatomically, PA is
divided into 3 types pyloric membrane or web
(57%), pyloric canal replaced by a solid cord of
tissue (34%), PA with a gap or gap aplasia
(9%).[2]
Epidermolysis bullosa (EB) consists of a
group of hereditary skin disorders, where the
primary cause is formation of blisters following
Case Report
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Dec 2007; Vol 17 ( No 4), Pp:369-374

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Pyloric Atresia Associated with Epidermolysis Bullosa. AA Sahebpoor, et al
minor trauma. EB is divided into 3 main types
according to the histopathologic location of the
bullae: Epidermolysis bullosa simplex (EBS),
Junctional epidermolysis bullosa (JEB), and
Dystrophic epidermolysis bullosa (DEB). Unlike
JEB as an autosomal recessive trait, EBS and
DEB can be inherited either as autosomal
recessive or as autosomal dominant. All three
types have been reported in association with PA,
although JEB is most frequently reported[3].
Evidence suggests that PA-EB association is a
distinct entity and is now referred to as the PA-
EB syndrome[4].
Because of septicemia, electrolyte imbalance
and protein loss seen in EB, the association of
PA-EB was thought to be fetal and it was
recommended in the past that surgical treatment
be withheld in these patients. Recently there has
been encouraging reports of survival among these
patients.

Case(s) Presentation
The study was conducted in the pediatric surgery
units of Boo-Ali hospital in Sari/Iran from 2003
to 2005, as an interventional study. Five patients
with PA associated with JEB were referred to us
from different hospitals.
Case 1: A premature baby girl was born by
Caesarean section at 32 weeks of gestational age.
The pregnancy was complicated by severe
vaginal bleeding. Antenatal sonography was
normal and there was no polyhydramnios. The
neonate had copious, nonbilious vomiting since
birth with mild epigastric dilation. She was
referred to us for surgical consultation on 8th day
of life. Physical examination showed multiple
bullous eruptions over all extremities. Biopsy
from one of these lesions was compatible with
JEB. An abdominal X-ray showed distended
stomach with no distal gas (Fig 1).
Fig 1- Plain abdominal radiograph revealing single gas bubble with no gas distally.

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Iran J Pediatr. Vol 17 (No 4); Dec 2007
Laparatomy revealed PA type 2 and
gastroduodenostomy was
feeding started on the 7th postoperative day and
was well tolerated. Skin lesions healed without
scar. She was seen regularly in outpatient clinic
and now at 3 years of age is doing well.
performed. Oral
Case 2: This 15-day old boy was referred to us
because of nonbilious vomiting. Since the 8th
day of life he developed bullous skin lesions all
over the body especially over the ankles and
hands. He was born by normal vaginal delivery
(NVD), with a birth weight of 2000 grams.
Antenatal ultrasound (U.S) was normal. Mother
had urinary tract infection during pregnancy and
received antibiotics. Abdominal plain X-ray
showed single bubble of gas. In the referring
hospital an upper GI series had revealed dilation
of stomach with no contrast beyond the pylorus
(Fig. 2). Biopsy of a fresh bulla showed JEB.
At laparatomy there was a dilated stomach
with a membrane at the pylorus (type 1). The
pyloric membrane was excised and Heineke-
Mikulicz pyloroplasty performed. Oral feeding
started on the 8th postoperative day and was well
tolerated. The patient was discharged 14 days
after operation.
On follow-up 1 month and 3 months post
operation he was doing well and all his skin
lesions were healed. He tolerated formula with no
vomiting.
Case 3: A 3-day old boy was referred to our
hospital for surgical consultation because of
nonbilious projectile vomiting. He was born by
C/S at 36 weeks gestational age. He weighed
2700 grams. Antenatal ultrasound scans showed
polyhydramnios. A plain abdominal X-ray
revealing single bubble with no distal gas
confirmed the diagnosis. Laparatomy was done at
day 5 of life. A type 2 PA was noted. Gastro-
duodenostomy was performed. The next day he
showed bullous eruptions on the palm and on
pressure sites as well. Biopsy of one of the
lesions was compatible with JEB. On day 5 post
operation we started oral feeding. The child had
an uneventful postoperative course and was
discharged. On follow-up 6 months after
operation he is doing well and has gained weight.
Case 4: A baby boy was born by NVD at term.
His weight was 2 kg. At the second day of life he
had copious nonbilious vomiting and on 11th day
he was referred to us. No antenatal ultrasound
was done. He also had bullae on his hand, feet
Fig 2. Upper gastrointestinal study showing dilated stomach and gastric outlet obstruction

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Pyloric Atresia Associated with Epidermolysis Bullosa. AA Sahebpoor, et al
and trunk. Biopsy of one fresh bulla showed JEB.
Because of a distended stomach as a single
bubble on plain radiography we suspected PA.
Laparatomy confirmed
gastroduodenostomy was performed. On day 5
post operation oral feeding was started. He was
discharged home and on follow-up 2 weeks later
was doing well. He has regular visits to clinic and
6 month post operation has no problem.
type 2 PA and
Case 5: This 5-day old boy was born by NVD,
and referred to us for nonbilious vomiting.
Antenatal ultrasonography
hydraminios. On Physical examination there
were multiple bullous eruptions over the
extremities. Biopsy of one of the lesions was
compatible with JEB. Abdominal X-ray showed
single bubble of gas. At laparatomy there was a
type 2 PA. Gastroduodenostomy was performed
with tube gastrostomy. One week post operation
he became septic and died of fulminant
septicemia on 12th postoperative day.
showed poly-
They were 4 boys and one girl. Mean age of
presentation was 8.4 days (3 to 15 days). Prenatal
ultrasound showed polyhydramnios in 3 and was
normal in 2 cases. There were multiple bullous
skin lesions over the extremities in all of the
patients. Biopsy of the fresh bullae was
compatible with JEB in all 5 patients. All patients
underwent laparatomy after stabilization. Four
neonates with type
gastroduodenostomy, and the one patient with
type 1 PA had excision of membrane and
pyloroplasty. By 6 to 36 months follow-up (Mean
21.6 months) all 4 infants survived and were
doing well.
2 PA underwent
Discussion
The earliest description of PA is credited to
Caleder in 1733[5], and Swinbure and Kohler first
described the association of PA and EB in
1968[6]. This association was then extensively
described by Teran.[7]
The typical presentation of PA is non bilious
vomiting soon after birth without abdominal
distention. The diagnosis is made easily on plain
abdominal X-ray, which shows a single gas
bubble representing the distended stomach with
no distal gas. Upper GI series is almost never
indicated as further investigation. It does not
provide additional information because air is an
effective and safe contrast medium. Antenatal
ultrasound may show polyhydramnios and
dilated stomach.[8] Prematurity and poly-
hydramnios are found in most of these patients
like what we saw in our first and third patients.
EB is an autosomal recessive gene affecting the
integrity of the basement membrane and
hemidesmosomes and the control of the normal
process of fibrosis occurring during the course of
wound healing.
Diagnosis of EB is based on clinical and
laboratory criteria. The lesions constitute of
blisters, crusted erosions and scar formation. The
conventional histological techniques used for the
diagnosis of EB are transmission electro-
microscopy and immunofluorescence mapping.
Of the 3 types of EB, JEB is mostly associated
with PA. Defects in at least six distinct genes
have been identified in JEB. All code for proteins
involved in the hemidesmosome/ anchoring
filament complex.[9, 10]
Prenatal diagnosis is possible for PA-EB first
by fetal DNA analysis and second by analysis of
fetal skin biopsy using electromicroscopy and
indirect immunoflueresence. Major ultrasound
sign of PA is gastric dilatation. In 1990 Meizner
and Carine described the Snow Flake sign, an
echogenic appearance of the amniotic fluid
during the second trimester of pregnancy
associated with EB.[11] Second trimester amniotic
fluid is usually anechoic and visualization of any
particle in it is pathologic.
Sicot et al. emphasize the difficulty of inter-
preting prenatal ultrasound findings where there
is no suggestive context.[12] In the literature most
of the prenatal diagnoses reported occurred in
cases with a positive family history of PA-EB.
The poor prognosis associated with this
syndrome has led some to attempt to diagnose
this condition prenatally when there is a positive
family history.
PA-EB is known to be caused by the ITGA6
or ITGB4 genes encoding for the integrin alpha/6
or beta/4 subunits, respectively.[13, 14] There are
many theories regarding the cause of PA in
patients with PA-EB. One hypothesis suggests

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373
that PA occurs as a result of intrauterine
complication of EB where the pyloric mucous
membrane is affected leading to sloughing with
subsequent scarring and fibrosis and obliteration
of the pyloric canal.[1, 15]
The surgical treatment of PA depends on the
type of atresia. In type 1 PA, membrane is
excised and Heieke-Mikulicz
performed.[16, 17] For type 2 atresia the surgical
treatment is excision of atretic segment and
gastroduodenostomy.[16,18] For type 3 also the
surgical treatment is gastroduodenostomy.[18]
Gastrojejunostomy is better to be avoided
because it is associated with 59% failure and
55% mortality.[19]
The association of PA with EB is well
documented and a plain abdominal X-ray should
be performed in all babies with EB to exclude
PA. The distribution of blisters in EB may be
localized or generalized. Blisters are frequently
present at birth, but it is important to remember
that they may manifest up to 48 hours after
birth.[2] Although the JEB with its autosomal
recessive pattern of inheritance has been reported
widely in association with PA , other types of EB
have also been documented.[3] Type 1 atresia
predominates in non-EB cases, and type 2 cases
are mostly associated with EB. Four of our
patients had type 2 PA and only our second
patient had type 1 PA.
Whereas the surgical management for PA is
straightforward, septicemia,
imbalance, protein loss and failure to thrive
complicates the severe exudative skin lesions,
often leading to death, and it has led to
recommendation that surgical treatment be
withheld in patients with PA-EB. Four of our
cases were stable before operation, and tolerated
it well. They were all well on follow-up visits.
Follow up was from 6 to 36 months (mean 21.6
months). Our fifth case was not in good condition
before operation and died of sepsis after
operation. Postoperatively all 4 survived patients
tolerated oral feeding well and went home with
no problem. Hayashi et al[20] and other
investigators also recommend that stable infants
with PA-EB should be treated surgically. Smad et
al reported 3 cases of PA-EB. One of them died
before operation, and one of the two that had
operation survived .They concluded that although
pyloroplasty
electrolyte
the prognosis is poor in this condition, surgery
should not be withheld on assumption of high
mortality.[4]
In some cases of PA-BA, a third phenomenon
is described: Alasia cutis congenita (ACC).
Maman et al. reported 5 newborns and 3 fetuses
with EB-PA-ACC association.[22]
A variety of urinary tract diseases like
ureterovesical junction obstruction leading to the
early development of hydronephrosis should be
suspected. So ultrasonography and cystoscopy
are recommended in all survivors with PA-EB
association. Wallerstein et al. reported 2 cases of
epidermolysis bullosa-pyloric atresia-obstructive
uropathy (EB-PA-OU).[21] The syndrome of EB-
PA-OU is a rare genetic entity of variable
severity manifested by skin finding of multiple
bullae and, infrequently, aplasia cutis congenita,
the gastrointestinal finding of pyloric or other
atresias, and progressive obstructive uropathy.
None of our 4 survived patients developed
urologic symptoms up to now.
If PA, which is a rare condition, is diagnosed
and treated on time, mortality and morbidity
becomes low. The main cause of death is
septicemia and electrolyte imbalance associated
with EB.
Conclusion
We add these 5 patients to the number of children
with EB-associated PA who underwent surgery,
survived and now are doing well. We recommend
surgical treatment for stabilized neonates with
PA-EB.
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