A form of junctional epidermolysis bullosa that is
associated with pyloric atresia and often results in death in the first year
Epidermolysis Bullosa Lethalis with Pyloric Atresia;
Aplasia Cutis Congenita with Gastrointestinal Atresia.
Approximately 70 cases have been reported. Junctional
epidermolysis bullosa accounts for approximately 1% of all epidermolysis
Autosomal recessive. The genetic defects have been
mapped to 17q11-qter and chromosome 2.
In junctional epidermolysis bullosa, blister
formation in the plane of the lamina lucida results in separation of the
epidermis from the basal lamina. The hemidesmosome content in the lamina
lucida of these patients often is significantly reduced in quantity and
quality (structural anomalies). The bullae per se heal without superficial
scarring; however, erosions provide an easy portal of entry for bacteria,
which trigger inflammation and marked fibrosis. Intestinal obstruction can
result from separation of the intestinal mucosal layer, which is followed by
a secondary inflammatory reaction and fibrosis, causing obliteration of the
intestinal lumen. The condition has been postulated to result from a
mutation in two of the integrin genes (integrin alpha-6 and integrin beta-4), which appears to affect the integrity
of the basement membrane, the hemidesmosomes, and the control of the normal
scarring process during wound healing. The sequence of events is initiated
by separation of the epidermis or intestinal mucosal layers from the basal
lamina. The resulting inflammatory reaction triggers massive fibrosis
involving the deep layers of the tissue and leading to damage of skin and
obstruction of the intestinal lumen. If aplasia cutis congenita is present,
mixed skin lesions with blisters and patchy lack of skin can be seen.
Based on the clinical findings of epidermolysis bullosa or
aplasia cutis congenita associated with gastrointestinal signs. Transmission
electron microscopy and immunofluorescence mapping can be used to confirm
the diagnosis. Elevated amniotic fluid α-fetoprotein levels have
been described in some cases.
Polyhydramnios in the last trimester and
premature delivery occur frequently. The skin may initially appear normal,
but there may already be areas of blistering and skin loss. Bullae form
easily in response to minor trauma. In the first year of life, a
pathognomonic, chronic perinasal, and/or perioral crusted lesion may appear.
One study reported mixed skin lesions, including blisters and a patchy lack
of skin, in all affected infants. All skin
layers are involved and show marked dystrophic changes. Nails may
be either absent or severely dystrophic. Almost all patients have intestinal
obstructions, especially membranous pyloric atresia or stenosis. Intestinal
obstruction results from proliferative connective tissue changes. Pyloric atresia presents with
nonbilious vomiting, which may be projectile. Esophageal atresia has been
described. Epidermolysis bullosa-like lesions may affect the respiratory
tract and cause acute respiratory failure. Commonly associated anomalies
include aplasia cutis congenita (43%) and obstruction at the
ureterovesical junction (14%), which may lead to bilateral
hydronephrosis. The high mortality of up to 80% in the first year of life
is most ...