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Xeroderma Pigmentosum

Xeroderma pigmentosum is a rare disorder


transmitted in an autosomal recessive
manner. It is characterized by photosensitivity,
pigmentary changes, premature skin aging,
and malignant tumor development .These
manifestations are due to a cellular
hypersensitivity to ultraviolet (UV) radiation
resulting from a defect in DNA repair.
Pathophysiology
The basic defect in xeroderma pigmentosum is
in nucleotide excision repair (NER), leading
to deficient repair of DNA damaged by UV
radiation.
Mortality/Morbidity
Individuals with this disease develop multiple
cutaneous neoplasms at a young age. Two
important causes of mortality are metastatic
malignant melanoma and squamous cell
carcinoma
_ace
ases of xeroderma pigmentosum are
.reported in persons of all races
Sex
An equal prevalence has been reported in
.males and females
Age
The disease is usually detected at age 1-2
.years
linical

The disease typically passes through 3 stages.


The skin is healthy at birth. Typically, the first
stage appears after age 6 months. This stage is
characterized by diffuse erythema, scalingseen
over light-exposed areas.With progression of the
disease, the skin changes appear on the lower
legs, the neck, and even the trunk in extreme
cases. While these features tend to diminish
during the winter months with decreased sun
exposure, as time passes, these findings
become permanent.
The second stage is characterized by
poikiloderma. Poikiloderma consists of
skin atrophy, telangiectasias, and mottled
hyperpigmentation and hypopigmentation,
The third stage is heralded by the
appearance of numerous malignancies,
including squamous cell carcinomas,
malignant melanoma, basal cell
carcinoma, and fibrosarcoma. These
malignancies may occur as early as age 4-
5 years and are more prevalent in sun-
exposed areas.
Neurologic problems are seen in nearly 20%
of patients with xeroderma pigmentosum,
Òistologic Findings

Òistologic features of actinic keratosis in an


individual with xeroderma pigmentosum. Note the
.atypia of the keratinocytes and the parakeratosis
ïreatment
ïhe goal of treatment is to protect the patient
from sunlight. ïhe use of sunscreens in
conjunction with other sun-avoidance
methods.
Oral retinoids have been shown to decrease the
incidence of skin cancer.
hemical therapy with 5-fluorouracil may be useful
for actinic keratoses.
The malignancies associated with xeroderma
pigmentosum should be completely excised.
chthyosis
Ichthyosis refers to a relatively
uncommon group of skin
disorders characterized by the
presence of excessive amounts of
dry surface scales. It is regarded
as a disorder of keratinization or
cornification, and it is due to
abnormal epidermal differentiation
or metabolism.
The ichthyosiform dermatoses may be
classified according to clinical
manifestations, genetic presentation and
histologic findings. Inherited and acquired
forms of ichthyosis have been described.
Five distinct types of inherited ichthyosis
are noted, as follows: ichthyosis vulgaris,
lamellar ichthyosis, epidermolytic
hyperkeratosis, congenital ichthyosiform
erythroderma, and X-linked ichthyosis.
_ace
In general, all races may be affected in
the inherited and acquired forms of
ichthyosis.
Sex
X-linked recessive ichthyosis is much
more prevalent in males.
linical
n ichthyosis vulgaris, dry skin and
follicular accentuation (keratosis
pilaris) usually appear at puberty.
Scaling is most prominent over the
trunk, abdomen, buttocks, and legs.
ïhe flexural areas, such as the
antecubital fossa, are spared. An
association may be present between
ichthyosis vulgaris and atopic
diseases.
ýamellar ichthyosis is a rare, autosomal
recessive, genetically heterogeneous skin
disease caused by mutations involving
multiple genetic loci. In classic lamellar
ichthyosis, children with the disease are
referred to as collodion babies and are
covered at birth by a thickened membrane
that subsequently is shed. The scaling of
the skin involves the whole body with no
sparing of the flexural creases.
In epidermolytic hyperkeratosis, the skin is
moist, red, and tender at birth. Bullae
formation may occur, which may become
infected and give rise to a foul skin odor.
Thick, generalized, verrucous scaling
occurs within a few days. ýocalized
scaling may be seen, especially in the
flexural creases.
In X-linked ichthyosis, generalized scaling is
present at or shortly after birth. This
scaling is most prominent over the
extremities, neck, trunk, and buttocks. The
flexural creases, palms, and soles are
spared.
ongenital ichthyosiform erythroderma (IE)
is a milder form of the disease that is
autosomal recessive in inheritance. IE
has been found to be caused by mutations
in the genes coding for transglutaminase.
Acquired ichthyosis usually occurs in adults and
manifests as small, white, fishlike scales that
frequently are concentrated on the extremities
but may be seen in a generalized distribution.
This form of ichthyosis may be associated with
Hodgkin lymphoma ,internal neoplasia eg
HIV ,sarcoidosis ,leukemia, systemic illness eg
chronic hepatitis ,hypothyroidism ,infection
or ,bone marrow transplantation ,malabsorption
the intake of certain medications that interfere
with sterol synthesis in epidermal cells eg,
nicotinic acid.
ýaboratory Studies
ichthyosis vulgaris - Skin biopsy
X-linked recessive ichthyosis ± Steroid sulfatase
(SïS) activity or levels of cholesterol sulfate and
genetic testing of amniotic fluid.
Epidermolytic hyperkeratosis - Skin biopsy and
keratin gene studies.
ýamellar ichthyosis ± Genetic analysis for
mutations in the gene for transglutaminase 1.
Acquired ichthyosis may be a marker of various
autoimmune disorders or malignancy. Acquired
ichthyosis may also be a marker of concomitant
infection with HIV in intravenous drug users .
B count with differential and bone marrow
aspirate.
Thyroid function tests ie, hypothyroidism.
Serum angiotensin converting enzyme and
lysozyme ie, sarcoidosis.
hest radiography ie, sarcoidosis, lymphoma, HIV,
tuberculosis.
Serum antinuclear antibody (ANA), ie, systemic
lupus erythematosus [SýE], systemic sclerosis.
Òistologic Findings
In ichthyosis vulgaris, the affected skin
displays mild hyperkeratosis and a
diminished granular layer in the epidermis,
while the dermis has normal features.
ïreatment
Medical are
Systemic
Oral retinoids display an impressive
antikeratinizing action in ichthyosiform
dermatoses. Etretinate (1 mg/kg/d) and
isotretinoin (2 mg/kg/d) have been shown to
reduce scaling, discomfort, and disfigurement.
Topical
Keratolytics,Emoilents.
Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of inherited


bullous disorders characterized by blister
formation in response to mechanical trauma.
Epidermolysis bullosa is classified into 3 major
categories, including (1) epidermolysis bullosa
simplex (intraepidermal skin separation), (2)
junctional epidermolysis bullosa (skin separation
in lamina lucida or central BMZ), and (3)
dystrophic epidermolysis bullosa (sublamina
densa BMZ separation).
Onset of epidermolysis bullosa is at birth or
shortly after. The exception occurs in mild
cases of epidermolysis bullosa simplex,
which may remain undetected until
adulthood or occasionally remain
undiagnosed.
Epidermolysis bullosa simplex

Epidermolysis bullosa simplex is a


collection of keratin disorders
characterized by intraepidermal blistering
with relatively mild internal involvement.
ýesions typically heal without scarring.
Most commonly, these diseases are
dominantly inherited,
Epidermolysis bullosa simplex
localized blistering at sites of
trauma
ëunctional epidermolysis bullosa

Junctional epidermolysis bullosas is a


collection of diseases characterized by
intralamina lucida blistering. Primary
subtypes include a lethal subtype termed
Herlitz or junctional epidermolysis bullosa
letalis, a nonlethal subtype termed
junctional epidermolysis bullosa mitis, and
a generalized benign type termed
generalized atrophic benign epidermolysis
.bullosa
Òerlitz subtype. ïhis severe disease is
characterized by generalized blistering
at birth, significant internal
involvement, and a poor prognosis.
Nonlethal junctional epidermolysis bullosa
Patients are manifested by generalized
blistering ,survive infancy and clinically
improve with age. They have scalp, nail,
and tooth abnormalities. Periorificial
erosions and hypertrophic granulation
tissue can be present. Mucous
membranes often are affected by
erosions, resulting in strictures. Some
patients with junctional epidermolysis
bullosa mitis can present with blistering
localized to the intertriginous regions.
|eneralized atrophic benign epidermolysis
bullosa

This is a relatively mild subtype


characterized by generalized cutaneous
blistering and presenting at birth. Blistering
activity is worsened by increased ambient
temperature, and blisters heal with a
distinctive atrophic appearance.
Oystrophic epidermolysis bullosa

This is a group of diseases caused by


defects of anchoring fibrils. Blisters heal
followed by dystrophic scarring. Formation
of milia (1- to 4-mm white papules) results
as a consequence of damage to hair
.follicles
Dominantly inherited dystrophic
epidermolysis bullosa

The onset of disease usually is at birth or


during infancy, with generalized blistering
as a common presentation. With
increasing age, an evolution to localized
blistering is present.
Oominantly inherited dystrophic
epidermolysis bullosa. ïhe blistering in
this disease often is localized and is
characterized by scarring and milia in
healed blister sites.
Recessively inherited epidermolysis bullosa

This group of diseases ranges from mild to


severe in presentation.
A localized form, termed recessively
inherited epidermolysis bullosa mitis, often
involves acral areas and nails but shows
little mucosal involvement.
Severe recessively inherited epidermolysis
bullosa, usually shows generalized
blistering at birth and subsequent
extensive dystrophic scarring that is most
prominent on the acral surfaces
_ecessively inherited dystrophic
epidermolysis bullosa
Histopatology
ïreatment

Prevention of infection is the preferred strategy.


With extensive areas of crusting and denudation,
a strict wound care regimen should be followed.
Such a regimen entails regular whirlpool therapy
followed by application of topical antibiotics. The
wound should be covered with semiocclusive
nonadherent dressings. Do not apply adhesive
tape directly to the skin. Self-adhering gauze or
tape is a better choice for keeping dressings in
.place
ï