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Bullous Congenital Ichthyosiform Erythroderma:

A Case Report
Rahmeh Fayez MD*

ABSTRACT
We report the case of a 16 year old male patient who presented to the dermatology clinic with spiny
hyperkeratosis in flexural areas and palmoplantar keratoderma. The patient gave history of occasional
localized blisters formation. Clinical findings and the histopathological picture fit the diagnosis of Bullous
Congenital Ichthyosiform Erythroderma. Family history is also positive for the same disease.

Key words: Bullous congenital ichthyosifom erythroderma, Epidermolytic, Hyperkeratosis


JRMS March 2011; 18(1): 66-70

Introduction

Case Report

Bullous congenital ichthyosiform erythroderma


(BCIE) which is also called epidermolytic
hyperkeratosis is a rare autosomal dominant disorder
(50% spontaneous mutation). It is estimated to affect
from 1 in 300,000 to 1 in 200,000 individuals.(1) It
was first described by Jean-Louis Brocq in 1902.(2)
BCIE is linked to keratin cluster on chromosome
12q and 17q, in genes encoding keratin 1 (K1) and
keratin 10 (K10).(3) The keratins are proteins that
form the intermediate cytoskeleton in the epidermal
cells, thereby maintaining the structural integrity of
the epidermis.(4)
BCIE is strikingly a heterogeneous group and
shows phenotypic variability in many families.
Factors that determine the phenotype and the
severity of the manifestations are the location of the
mutation in the gene itself (if it occurs in a critical
region for a specific function), secondly the type of
the mutation.(5)
An epidermal nevus may represent somatic
mosaicism for keratin gene mutation which
produces generalized BCIE in the next generation.
This phenomenon is explained by a postzygotic
mutation which can be passed on to the next
generation.(6,7)

A 16 year old Jordanian male patient presented to


the dermatology clinic at Prince Rashed Hospital
with dark, warty, scaly lesions in the flextures and
palmoplantar keratoderma. The patient also gave
history of occasional blisters formation mainly
during summer, the frequency of these blisters
became less as he got older. Nail, hair and teeth are
normal. The patient was born to consanguineous
marriage. He was a product of full term smooth
pregnancy with normal birth weight and length.
Shortly after birth the patient developed widespread
blisters which ruptured rapidly leaving wide area of
denuded skin, this necessitated admission to the
intensive care unit. Although the frequency of
blisters and erythema decreased with age he
continued to have attacks of widespread bullae with
secondary bacterial infection. His school
performance is good. He has positive family history
(Fig.1); one sister has similar condition, while his
father has severe palmoplantar keratoderma as
solitary finding.
Clinical Examination
On presentation, the patient was depressed and
avoided eye contact. Body fetid odour was

*From Department of Dermatology, Prince Rashed Bin Al-Hassan Hospital, (PRHH), Irbid-Jordan
Correspondence should be addressed to Dr. R. Fayez, (PRHH), E- mail: rahmehfyz@yahoo.com
Manuscript received December 1, 2009. Accepted March 11, 2010

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Fig. 1. Pedigree of the patients family


Squares represent male family members and circles female family members. A slash indicates that the person has died. A double line
indicates a consanguineous marriage. Open symbols represent healthy persons, solid symbols represent patients with BCIE.

noticed. Well demarcated mildly erythematous scaly


corrugated plaques over the neck and abdomen
were found (Fig. 2). The scales at those areas were
fine and white. Flexures, especially the axillae,
showed spiny ridges (Fig. 3), the inguinal area
showed bullous eruption, some of them ruptured
leaving tender denuded areas. Smooth palmoplantar
hyperkeratotic surface was evident (Fig. 4a, 4b).
Palmoplantar hyperkeratosis had erythematous
border and caused limitation of finger movement
i.e., digital contractures.
Laboratory Findings
Histopathological examination of lesional skin
showed classic epidermolytic hyperkeratosis i.e.,
hyperkeratosis papillomatosis, acanthosis and
vacuolization of the superficial epidermal cells with
prominent eosinophilic granules (Fig. 5a, 5b). Other
investigations were all normal.
Management
The patient was started on emollients. Keratolytics
as salicylic acid and urea lotion were used
intermittently. Attacks of bacterial infection were
treated by systemic and topical antibiotics. Systemic
acitretin was used for about one month (25 mg
daily) and it gave a significant response. Acitretin
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was discontinued because of elevation of liver


enzymes which went back to normal level after one
month of discontinuation of the drug.

Discussion
BCIE is a type of erythroderma that affects infants
and children. BCIE clinically presents at birth with
generalized erythema, blisters and erosions with or
without focal areas of hyperkeratosis.(8) Sepsis and
electrolytes imbalance can occur as secondary
events during neonatal period.(8) In subsequent
months erythema and blistering improve but patient
goes on to develop hyperkeratosis and scaling.
During childhood and adulthood, the patient usually
presents
with
localized
or
generalized
hyperkeratosis with rare focal bullae secondary to
bacterial infections. The scales are characteristically
linear, warty, with spiny ridges mainly in the
flexures and the nape of the neck. Thick scales
especially in the intertrignous areas may shed with
full thickness stratum corneum leaving tender and
denuded areas. Scale shedding and maceration in
conjunction with secondary bacterial infection
produce a foul odor. Involvement of the palms and
soles occur in about 60% of the patients, resulting in
recurrent painful fissures and contractures.(9)
Although typically those patients with K1 mutation
67

Fig. 2. Well demarcated erythematous hyperkeratotic


corrugated plaques over the abdomen and antecubital fossae

Fig. 3. Right axilla showing linear (streaky), warty scales with


spiny ridges

Fig. 4a & 4b. Palmoplantar keratoderma.

Fig. 5a. Epidermolytic hyperkeratosis. Hyperkeratosis,


papillomatosis, acanthosis and vacuolization of the superficial
epidermal cells. (Hematoxylin & eosin, x10)

tend to have palmoplantar keratoderma and those


with K10 mutation do not, a recent report showed
epidermolytic hyperkeratosis with palmoplantar
keratoderma in patient with K10 mutation.(10)
BCIE is a heterogeneous group so there are at least
six recognizable clinical phenotypes; 3 types with
no palm/sole hyperkeratosis (NPS 1-3) and 3 types
with palm/sole hyperkeratosis (PS 1-3).(1,11,12)
Patients with NPS-1 type have normal
palmoplantar surface, a hystrix scale, is generalized,
no erythroderma, have positive history of blistering
and may have abnormal gait. Patients with NPS-2
type are similar to NPS-1, but the scales here are
brown and have no gait abnormality. Patients with
NPS-3 type have no palmoplantar hyperkeratosis but
the palmoplantar surface is hyperlinear, fine and
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Fig. 5b. Epidermolytic hyperkeratosis. Large eosinophilic


keratohyaline granules in the vacuolated expanded granular cell
layers. (Hematoxylin & eosin, x40)

white scales, erythroderma, a positive history of


blistering and may have abnormal gait.
Patients with PS-1 type have smooth palmoplantar
hyperkeratotic surface, no digital contractures, mild
scales, no erythroderma, localized blistering and
suffer no gait abnormality. Those with PS-2 type
have smooth palmoplantar hyperkeratotic surface
(severe, erythematous border), digital contracture,
fine white scales that may peel, generalized mild to
moderate erythroderma, positive blistering and may
have gait abnormality. Patients with PS-3 type have
cerebriform palmoplantar hyperkeratotic surface, no
digital contracture, tan scales, is generalized, no
erythroderma, neonatal blistering and no gait
abnormality.
There are rare reported associations like rickets,(13)
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retarded growth and delayed developmental


milestones.(1)
The diagnosis of BCIE is primarily clinical. Our
patient most likely has BCIE PS- 2 type.
The
differential diagnoses during neonatal period include
other
neonatal
blistering
disorders
like
epidermolysis bullosa, staphylococcal scalded skin
syndrome, herpetic infection, toxic epidermal
necrolysis, non bullous congenital ichthyosiform
erythroderma and incontinentia pigmenti. The
differential diagnoses during childhood and
adulthood period include other forms ichthyosis.
(8,11, 12)
The former differential diagnoses can be
easily excluded by a histopathological study of
patients skin biopsy. BCIE was the first disease to
be diagnosed microscopically following prenatal
skin biopsy.(14)
Histopathology
The histopathological finding of BCIE is
characteristic and is referred to either epidermolytic
hyperkeratosis or a granular degeneration. It is
present in bullous and non-bullous forms. The
histopathological
features
include
compact
hyperkeratosis, marked thickening of granular cell
layer that contains an increased number of giant
irregularly shaped keratohyaline granules, and
vacuolization of the stratum granulosum and upper
stratum spinosum. The bullae arise intraepidermally
through separation of edematous cells from one
another i.e. epidermolysis. Mitotic figures are five
times more numerous than in normal epidermis.(15)

glycol. Antiseptics such as antibacterial soaps can be


used to decrease bacterial colonization. Bacterial
infection should be treated promptly by topical or
systemic antibiotics and discontinued after healing
to avoid developing antibiotic resistance.(8,11)
Systemic (oral) retinoids such as acitretin or
etretinate are considered by some authors to be the
treatment of choice for disorders of keratinization.(3,
14)
Retinoids dramatically reduce hyperkeratosis but
they are also increase epidermal fragility and blisters
formation, therefore should be started at a low initial
dose and gradually increased until the lowest
maintenance dose has been determined.
Topical calcipotriol is safe and effective in treating
adolescents and adults with disorder of
keratinization. It has been reported to be used
successfully in a nine year old boy with BCIE for
more than three years with no adverse effects.(3)
Gene therapy using small interfering RNAs
(siRNAs) technology is one of the most promising
therapeutic options for dominant monogenic skin
disorders. Small interfering RNAs (siRNAs) have
been designed to silence a mutant allele with little or
no effect on the corresponding wild-type allele
expression.(16)
BCIE is a chronic disease but fortunately the
severity of the disease appears to decrease with
age.(6) Genetic counseling and prenatal diagnosis are
now available using fetal skin biopsy and DNA
screening techniques to identify K1 + K10 mutation
from chorionic villus sampling.(4)

Conclusion
Treatment
Treatment is mostly symptomatic and is aimed at
the ichthyotic skin as well as the bacterial infection.
Treatment depends on the age: neonatal period,
childhood, and adulthood.
On the whole, emollients, keratolytics and
antibiotics are the mainstay of treatment. In the
neonatal period the patients require management in
the intensive care unit to provide isolation and to
prevent or to treat dehydration, temperature
instability and cutaneous infection. To decrease
blisters formation and hasten erosions healing, the
affected neonates should be handled gently,
protective padding and lubricants should be used.
During childhood and adulthood the treatment is
aimed at managing the ichthyotic skin by hydration,
lubrication and keratolysis.(11)
Keratolytic creams and lotions may contain urea,
salicylic acid, alphahydroxy acids or propylene
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We report this case to reemphasize the phenotypic


heterogeneity of BCIE even within the same family.
In addition, reporting of such cases is helpful to
estimate the real incidence of rare genodermatosis.

References
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