9 December 2009 - Case of the Week
#163
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Thanks to Dr.
Kim
Billingham,
Case of the Week #163
Clinical
History
A 9 year old boy presented with a
five day history of lower abdominal pain and nausea. There was no history of trauma. Laparotomy showed a perforated sigmoid colon
and faecal peritonitis. His past medical
history was significant for bilateral herniotomies as an infant.
Nine years previously, the pathology
lab received a right hemicolectomy specimen from the boy’s mother, after her
caecum perforated during a caesarean section.
Sections from the sigmoid colon of
the 9 year old boy were obtained:
Micro images:
20x
40x
100x
400x
What is your diagnosis?
Diagnosis:
Ehlers-Danlos syndrome, vascular
type (type IV)
Discussion:
The sigmoid colon included a 2 mm
focus of full thickness perforation.
Serial sectioning showed additional areas of mucosal ulceration, with
the bowel wall thickness varying from 1 to 3 mm. The histology showed areas of "punched
out" mucosal necrosis, with underlying segmental absence of the muscularis
propria. It was replaced by a cellular,
reactive fibroblastic proliferation, accompanied by prominent eosinophils. These areas were present in several segments
along the circumference of the bowel wall and in various locations along the length
of the sigmoid colon. Evidence of
peritonitis was also present. No vasculitis,
inflammatory bowel disease or diverticuli were noted.
The slides from the mother’s prior hemicolectomy
had features similar to those in her son’s specimen. Genetic testing of the mother showed she was
markedly deficient in collagen type 3, with a mutation of one of her two COL3A1
genes.
Ehlers-Danlos syndrome (EDS) is an inherited
heterogenous group of connective tissue disorders characterized by abnormal
collagen synthesis (eMedicine, Wikipedia). Six variants of EDS have been described, based
on clinical and molecular features (Am J Med Genet 1998;77:31). Clinical symptoms vary by clinical variant,
and include skin hyperextensibility and fragility/poor healing; joint
hyperextensibility with a propensity to dislocation; eye symptoms with corneal
rupture and retinal detachment; kyphoscoliosis and rupture of the colon and
large arteries.
Vascular type EDS (type IV -
autosomal dominant inheritance) is caused by a mutation in the COL3A1 gene (J Nippon Med Sch 2008;75:254), and is associated with a reduced median
survival of only 48 years. There are
three distinct types of mutations, which affect either the rate of synthesis, the
secretion of type III procollagen or result in structurally abnormal type III
collagen. Neonates have an increased
incidence of clubfoot and hip dislocation, and rarely have subarachnoid
hemorrhage (Am J Clin Pathol 1990;93;579).
In children, inguinal hernia, pneumothorax and recurrent joint dislocation
or subluxation are common. The skin is translucent
with visible veins and is easily bruised. Distinctive facial features are often present,
including protruding eyes, a thin nose and lips, sunken cheeks and a small
chin. Blood vessels and intestines are
typically rich in type III collagen, and adult patients often present with
vascular rupture/dissection or gastrointestinal perforation. Uterine rupture may occur during pregnancy, particularly
at delivery.
Although there is no specific treatment
for EDS, preventative measures are recommended, and there may be a role for
high dose Vitamin C.
Additional comment from author: The areas
of mucosal necrosis, not shown in the pictures submitted, were all overlying
areas in which the muscularis propria was absent (this is illustrated in the
pictures submitted), and one of these areas formed the site of the perforation.
Perforations are often multiple in these patients (most frequently occurring in
the sigmoid colon) and the changes in the colon in this case ranged from
defects in the muscularis propria to defects in the muscularis propria and
mucosa to the area of perforation. The
colon, uterus and blood vessel walls are all rich in type III collagen, and
patients with Ehlers-Danlos syndrome (type IV) have quantitative or qualitative
defects in their type III collagen, leading to areas of structural weakness in
these organs. This predisposes them to
spontaneous gastrointestinal perforation, vascular dissection and uterine
rupture in pregnancy.
Additional references: Arch Pathol Lab Med
1993;117:989, J Clin
Neuromuscular Dis 2009;11:81, Intern Med 2009;48:717
Nat Pernick, M.D., President,
and Kara Hamilton, M.S., Associate
Medical Editor
PathologyOutlines.com, Inc.
30100 Telegraph Road, Suite 408
Bingham Farms,
Telephone: 248/646-0325
Email: NatPernick@Hotmail.com
Alternate email: NatPernick@gmail.com