Bullous Congenital Ichthyosiform Erythroderma: A Case Report
Bullous Congenital Ichthyosiform Erythroderma: A Case Report
Bullous Congenital Ichthyosiform Erythroderma: A Case Report
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<strong>Bullous</strong> <strong>Congenital</strong> <strong>Ichthyosiform</strong> <strong>Erythroderma</strong>:<br />
A <strong>Case</strong> <strong>Report</strong><br />
Rahmeh Fayez MD*<br />
ABSTRACT<br />
We report the case of a 16 year old male patient who presented to the dermatology clinic with spiny<br />
hyperkeratosis in flexural areas and palmoplantar keratoderma. The patient gave history of occasional<br />
localized blisters formation. Clinical findings and the histopathological picture fit the diagnosis of <strong>Bullous</strong><br />
<strong>Congenital</strong> <strong>Ichthyosiform</strong> <strong>Erythroderma</strong>. Family history is also positive for the same disease.<br />
Key words: <strong>Bullous</strong> congenital ichthyosifom erythroderma, Epidermolytic, Hyperkeratosis<br />
JRMS March 2011; 18(1): 66-70<br />
Introduction<br />
<strong>Bullous</strong> congenital ichthyosiform erythroderma<br />
(BCIE) which is also called epidermolytic<br />
hyperkeratosis is a rare autosomal dominant disorder<br />
(50% spontaneous mutation). It is estimated to affect<br />
from 1 in 300,000 to 1 in 200,000 individuals. (1) It<br />
was first described by Jean-Louis Brocq in 1902. (2)<br />
BCIE is linked to keratin cluster on chromosome<br />
12q and 17q, in genes encoding keratin 1 (K1) and<br />
keratin 10 (K10). (3) The keratins are proteins that<br />
form the intermediate cytoskeleton in the epidermal<br />
cells, thereby maintaining the structural integrity of<br />
the epidermis. (4)<br />
BCIE is strikingly a heterogeneous group and<br />
shows phenotypic variability in many families.<br />
Factors that determine the phenotype and the<br />
severity of the manifestations are the location of the<br />
mutation in the gene itself (if it occurs in a critical<br />
region for a specific function), secondly the type of<br />
the mutation. (5)<br />
An epidermal nevus may represent somatic<br />
mosaicism for keratin gene mutation which<br />
produces generalized BCIE in the next generation.<br />
This phenomenon is explained by a postzygotic<br />
mutation which can be passed on to the next<br />
generation. (6,7)<br />
*From Department of Dermatology, Prince Rashed Bin Al-Hassan Hospital, (PRHH), Irbid-Jordan<br />
Correspondence should be addressed to Dr. R. Fayez, (PRHH), E- mail: rahmehfyz@yahoo.com<br />
Manuscript received December 1, 2009. Accepted March 11, 2010<br />
<strong>Case</strong> <strong>Report</strong><br />
A 16 year old Jordanian male patient presented to<br />
the dermatology clinic at Prince Rashed Hospital<br />
with dark, warty, scaly lesions in the flextures and<br />
palmoplantar keratoderma. The patient also gave<br />
history of occasional blisters formation mainly<br />
during summer, the frequency of these blisters<br />
became less as he got older. Nail, hair and teeth are<br />
normal. The patient was born to consanguineous<br />
marriage. He was a product of full term smooth<br />
pregnancy with normal birth weight and length.<br />
Shortly after birth the patient developed widespread<br />
blisters which ruptured rapidly leaving wide area of<br />
denuded skin, this necessitated admission to the<br />
intensive care unit. Although the frequency of<br />
blisters and erythema decreased with age he<br />
continued to have attacks of widespread bullae with<br />
secondary bacterial infection. His school<br />
performance is good. He has positive family history<br />
(Fig.1); one sister has similar condition, while his<br />
father has severe palmoplantar keratoderma as<br />
solitary finding.<br />
Clinical Examination<br />
On presentation, the patient was depressed and<br />
avoided eye contact. Body fetid odour was<br />
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4<br />
5<br />
Fig. 1. Pedigree of the patient’s family<br />
Squares represent male family members and circles female family members. A slash indicates that the person has died. A double line<br />
indicates a consanguineous marriage. Open symbols represent healthy persons, solid symbols represent patients with BCIE.<br />
noticed. Well demarcated mildly erythematous scaly<br />
corrugated plaques over the neck and abdomen<br />
were found (Fig. 2). The scales at those areas were<br />
fine and white. Flexures, especially the axillae,<br />
showed spiny ridges (Fig. 3), the inguinal area<br />
showed bullous eruption, some of them ruptured<br />
leaving tender denuded areas. Smooth palmoplantar<br />
hyperkeratotic surface was evident (Fig. 4a, 4b).<br />
Palmoplantar hyperkeratosis had erythematous<br />
border and caused limitation of finger movement<br />
i.e., digital contractures.<br />
Laboratory Findings<br />
Histopathological examination of lesional skin<br />
showed classic epidermolytic hyperkeratosis i.e.,<br />
hyperkeratosis papillomatosis, acanthosis and<br />
vacuolization of the superficial epidermal cells with<br />
prominent eosinophilic granules (Fig. 5a, 5b). Other<br />
investigations were all normal.<br />
Management<br />
The patient was started on emollients. Keratolytics<br />
as salicylic acid and urea lotion were used<br />
intermittently. Attacks of bacterial infection were<br />
treated by systemic and topical antibiotics. Systemic<br />
acitretin was used for about one month (25 mg<br />
daily) and it gave a significant response. Acitretin<br />
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was discontinued because of elevation of liver<br />
enzymes which went back to normal level after one<br />
month of discontinuation of the drug.<br />
Discussion<br />
BCIE is a type of erythroderma that affects infants<br />
and children. BCIE clinically presents at birth with<br />
generalized erythema, blisters and erosions with or<br />
without focal areas of hyperkeratosis. (8) Sepsis and<br />
electrolytes imbalance can occur as secondary<br />
events during neonatal period. (8) In subsequent<br />
months erythema and blistering improve but patient<br />
goes on to develop hyperkeratosis and scaling.<br />
During childhood and adulthood, the patient usually<br />
presents with localized or generalized<br />
hyperkeratosis with rare focal bullae secondary to<br />
bacterial infections. The scales are characteristically<br />
linear, warty, with spiny ridges mainly in the<br />
flexures and the nape of the neck. Thick scales<br />
especially in the intertrignous areas may shed with<br />
full thickness stratum corneum leaving tender and<br />
denuded areas. Scale shedding and maceration in<br />
conjunction with secondary bacterial infection<br />
produce a foul odor. Involvement of the palms and<br />
soles occur in about 60% of the patients, resulting in<br />
recurrent painful fissures and contractures. (9)<br />
Although typically those patients with K1 mutation<br />
67
Fig. 2. Well demarcated erythematous hyperkeratotic<br />
corrugated plaques over the abdomen and antecubital fossae<br />
Fig. 3. Right axilla showing linear (streaky), warty scales with<br />
spiny ridges<br />
Fig. 4a & 4b. Palmoplantar keratoderma.<br />
Fig. 5a. Epidermolytic hyperkeratosis. Hyperkeratosis,<br />
papillomatosis, acanthosis and vacuolization of the superficial<br />
epidermal cells. (Hematoxylin & eosin, x10)<br />
Fig. 5b. Epidermolytic hyperkeratosis. Large eosinophilic<br />
keratohyaline granules in the vacuolated expanded granular cell<br />
layers. (Hematoxylin & eosin, x40)<br />
tend to have palmoplantar keratoderma and those<br />
with K10 mutation do not, a recent report showed<br />
epidermolytic hyperkeratosis with palmoplantar<br />
keratoderma in patient with K10 mutation. (10)<br />
BCIE is a heterogeneous group so there are at least<br />
six recognizable clinical phenotypes; 3 types with<br />
no palm/sole hyperkeratosis (NPS 1-3) and 3 types<br />
with palm/sole hyperkeratosis (PS 1-3). (1,11,12)<br />
Patients with NPS-1 type have normal<br />
palmoplantar surface, a hystrix scale, is generalized,<br />
no erythroderma, have positive history of blistering<br />
and may have abnormal gait. Patients with NPS-2<br />
type are similar to NPS-1, but the scales here are<br />
brown and have no gait abnormality. Patients with<br />
NPS-3 type have no palmoplantar hyperkeratosis but<br />
the palmoplantar surface is hyperlinear, fine and<br />
white scales, erythroderma, a positive history of<br />
blistering and may have abnormal gait.<br />
Patients with PS-1 type have smooth palmoplantar<br />
hyperkeratotic surface, no digital contractures, mild<br />
scales, no erythroderma, localized blistering and<br />
suffer no gait abnormality. Those with PS-2 type<br />
have smooth palmoplantar hyperkeratotic surface<br />
(severe, erythematous border), digital contracture,<br />
fine white scales that may peel, generalized mild to<br />
moderate erythroderma, positive blistering and may<br />
have gait abnormality. Patients with PS-3 type have<br />
cerebriform palmoplantar hyperkeratotic surface, no<br />
digital contracture, tan scales, is generalized, no<br />
erythroderma, neonatal blistering and no gait<br />
abnormality.<br />
There are rare reported associations like rickets, (13)<br />
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etarded growth and delayed developmental<br />
milestones. (1)<br />
The diagnosis of BCIE is primarily clinical. Our<br />
patient most likely has BCIE PS- 2 type. The<br />
differential diagnoses during neonatal period include<br />
other neonatal blistering disorders like<br />
epidermolysis bullosa, staphylococcal scalded skin<br />
syndrome, herpetic infection, toxic epidermal<br />
necrolysis, non bullous congenital ichthyosiform<br />
erythroderma and incontinentia pigmenti. The<br />
differential diagnoses during childhood and<br />
adulthood period include other forms ichthyosis.<br />
(8,11, 12)<br />
The former differential diagnoses can be<br />
easily excluded by a histopathological study of<br />
patient΄s skin biopsy. BCIE was the first disease to<br />
be diagnosed microscopically following prenatal<br />
skin biopsy. (14)<br />
Histopathology<br />
The histopathological finding of BCIE is<br />
characteristic and is referred to either epidermolytic<br />
hyperkeratosis or a granular degeneration. It is<br />
present in bullous and non-bullous forms. The<br />
histopathological features include compact<br />
hyperkeratosis, marked thickening of granular cell<br />
layer that contains an increased number of giant<br />
irregularly shaped keratohyaline granules, and<br />
vacuolization of the stratum granulosum and upper<br />
stratum spinosum. The bullae arise intraepidermally<br />
through separation of edematous cells from one<br />
another i.e. epidermolysis. Mitotic figures are five<br />
times more numerous than in normal epidermis. (15)<br />
Treatment<br />
Treatment is mostly symptomatic and is aimed at<br />
the ichthyotic skin as well as the bacterial infection.<br />
Treatment depends on the age: neonatal period,<br />
childhood, and adulthood.<br />
On the whole, emollients, keratolytics and<br />
antibiotics are the mainstay of treatment. In the<br />
neonatal period the patients require management in<br />
the intensive care unit to provide isolation and to<br />
prevent or to treat dehydration, temperature<br />
instability and cutaneous infection. To decrease<br />
blisters formation and hasten erosions healing, the<br />
affected neonates should be handled gently,<br />
protective padding and lubricants should be used.<br />
During childhood and adulthood the treatment is<br />
aimed at managing the ichthyotic skin by hydration,<br />
lubrication and keratolysis. (11)<br />
Keratolytic creams and lotions may contain urea,<br />
salicylic acid, alphahydroxy acids or propylene<br />
glycol. Antiseptics such as antibacterial soaps can be<br />
used to decrease bacterial colonization. Bacterial<br />
infection should be treated promptly by topical or<br />
systemic antibiotics and discontinued after healing<br />
to avoid developing antibiotic resistance. (8,11)<br />
Systemic (oral) retinoids such as acitretin or<br />
etretinate are considered by some authors to be the<br />
treatment of choice for disorders of keratinization. (3,<br />
14) Retinoids dramatically reduce hyperkeratosis but<br />
they are also increase epidermal fragility and blisters<br />
formation, therefore should be started at a low initial<br />
dose and gradually increased until the lowest<br />
maintenance dose has been determined.<br />
Topical calcipotriol is safe and effective in treating<br />
adolescents and adults with disorder of<br />
keratinization. It has been reported to be used<br />
successfully in a nine year old boy with BCIE for<br />
more than three years with no adverse effects. (3)<br />
Gene therapy using small interfering RNAs<br />
(siRNAs) technology is one of the most promising<br />
therapeutic options for dominant monogenic skin<br />
disorders. Small interfering RNAs (siRNAs) have<br />
been designed to silence a mutant allele with little or<br />
no effect on the corresponding wild-type allele<br />
expression. (16)<br />
BCIE is a chronic disease but fortunately the<br />
severity of the disease appears to decrease with<br />
age. (6) Genetic counseling and prenatal diagnosis are<br />
now available using fetal skin biopsy and DNA<br />
screening techniques to identify K1 + K10 mutation<br />
from chorionic villus sampling. (4)<br />
Conclusion<br />
We report this case to reemphasize the phenotypic<br />
heterogeneity of BCIE even within the same family.<br />
In addition, reporting of such cases is helpful to<br />
estimate the real incidence of rare genodermatosis.<br />
References<br />
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