Xeroderma pigmentosum: report of two cases and review of ... - JPAD

Journal of Pakistan Association of Dermatologists 2012;22 (3):279-282.
Address for correspondence
Dr. Sankha Koley,
Subhankar Sarani;
Bankura-722101; West Bengal, India
Email: skoley@gmail.com
sankhakoley@gmail.com
Mobile: 9339688964
Case Report
Xeroderma pigmentosum: report of two cases
and review of the literature
Abstract
Introduction
Sankha Koley*, Sanjiv V. Choudhary**, Soumen Choudhury†, Shilpi Sharma*, Tanmoy
Mukherjee*, Kalyan Khan
*Dept of Dermatology, North Bengal Medical College, West Bengal
**Dept of Dermatology, J.N.M.C. Sawangi, Wardha, Maharastra
†Dept of Ophthalmology, Barddhaman Medical College, West Bengal
Dept of Pathology, North Bengal Medical College, West Bengal
Xeroderma pigmentosum (XP) occurs due to molecular defects in the genes involved in nucleotide
excision repair of ultraviolet-induced DNA lesions. Patients with XP have a risk of developing skin
cancer about 1000 times more than that of the general population. We report a classical presentation
in a 6-year-child and advanced squamous cell carcinoma in a 24-year old man.
Key words
Xeroderma pigmentosum, poikiloderma, photosensitive rash, squamous cell carcinomas.
Xeroderma pigmentosum (XP) is a rare
autosomal recessive disease occurring in
subjects with molecular defects in genes
involved in nucleotide excision repair (NER) of
ultraviolet-induced DNA lesions.
In 1874, Hebra and Kaposi used the term
‘xeroderma’ for this dry, dyspigmented
condition of skin. 1 In 1882, Kaposi added
‘pigmentosum’ to coin the term ‘xeroderma
pigmentosum’. 2 The hallmark of XP is UVinduced
skin hypersensitivity manifesting as
degenerative and proliferative cutaneous
changes including hyperpigmentation, skin
atrophy, poikiloderma, actinic keratosis, basal
cell carcinoma (BCC), squamous cell carcinoma
(SCC) and melanoma. 3,4 We present two
classical cases of XP.
Case report
A 6-year-old boy presented with ‘salt and
pepper’ pigmentary changes all over his body
and photosensitivity. The lesions appeared since
the age of 2 years. General examination revealed
extensive hyperpigmented and hypopigmented
lesions all over the body; more so on exposed
areas (Figures 1 and 2). There was no history of
other family members having XP. He had short
stature with neurological problems like mental
retardation, dysarthria and ataxia.
A 24-year-old male with hyperpigmented spots
all over body (varying in size from 2-4 mm and
few were raised from skin) presented to our
outdoor patient department for evaluation of a
growth on right cheek involving the right eye. A
tumor with cauliflower like growth, 5 cm X 4
cm, was noted with a non-healing ulcer infested
with maggots (Figures 3). It bled on touching.
The growth was removed and histopathology
showed it to be SCC.
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Journal of Pakistan Association of Dermatologists 2012;22 (3):279-282.
Figure 1 Case 1, poikiloderma on face.
Figure 2 Case 1, poikiloderma on arm and shoulder.
The sequence of pathological events in the
patient were the appearance of irregular
hyperpigmentation of the skin at 2 years of age,
photosensitive rash with rough-surfaced growths
(solar keratoses) since the age of 7 years and
Figure 3 Case 2, poikiloderma on face with
fungating SCC infested with maggots.
SCC since last 6 months. The patient did not
suffer from any neurodegenerative abnormalities
or impairment of intelligence. Till the time of
presentation, he had neither received any
treatment nor did he get any education regarding
protection from sun-exposure.
Discussion
The basic defect in XP is in nucleotide excision
repair (NER), leading to deficient repair of DNA
damaged by UV radiation. This extensively
studied process consists of the removal and
replacement of damaged DNA with new DNA.
Seven xeroderma pigmentosum repair genes
(XPA through XPG) have been identified. A XP
variant has also been described (Table 1). This
variant type is clinically indistinguishable from
classical XP but there is a defect in postreplication
DNA repair following UV exposure,
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Journal of Pakistan Association of Dermatologists 2012;22 (3):279-282.
Table 1 Classification of xeroderma pigmentosum.
Type Gene Locus Description
Type A, I, XPA XPA 9q22.3 Classical form of XP.
Type B, II, XPB XPB 2q21 XP group B.
Type C, III, XPC XPC 3p25 XP group C.
Type D, IV, XPD XPD ERCC6 19q13.2-q13.3 , 10q11
XP group D or De Sanctis-Cacchione
syndrome. May be considered a subtype of
XPD.
Type E, V, XPE DDB2 11p12-p11 XP group E.
Type F, VI, XPF ERCC4 16p13.3-p13.13 XP group F.
Type G, VII, XPG RAD2 ERCC5 13q33 XP group G and COFS syndrome type 3.
Type V, XPV POLH 6p21.1-p12
Box Kaplan-Meier survival curve
90% probability of surviving to age 13 years
80% probability of surviving to 28 years
70% probability of surviving to 40 years
Overall, life expectancy of patients with XP reduced
by 30 years
rather than nucleotide excision repair. 3
As with most autosomal recessive disorders,
usually no family history is present. But a
history of consanguinity among parents may be
elicited. The disease typically passes through 3
stages. The skin is healthy at birth. Typically, at
age of age 6 months, there is diffuse erythema,
scaling, and freckles on light-exposed areas,
appearing initially on the face. The second stage
is characterized by poikiloderma (skin atrophy,
telangiectasias, and mottled hyperpigmentation
and hypopigmentation). The third stage is
heralded by the appearance of numerous
malignancies, including basal cell carcinoma,
squamous cell carcinomas, malignant
melanoma, and fibrosarcoma. These
malignancies may occur as early as age 4-5
years and are more prevalent in sun-exposed
areas.
Neurologic problems develop due to premature
death of nerve cells and are seen in nearly 20%
of patients with XP, more commonly in groups
XPA and XPD. 5 The problems include loss of
XP variant. Due to mutation in a gene that
codes for a specialized DNA polymerase
called polymerase-η (eta).
fine motor control, rigidity, ataxia, spasticity,
hyporeflexia or areflexia, chorea, motor neuron
signs or segmental demyelination, sensorineural
deafness and progressive mental retardation. The
first XP case with neurological signs was
described by Dr. Albert Neisser. 6 In 1932,
DeSanctis and Cacchione 7 helped to coin the
term "De Sanctis-Cacchione syndrome" to apply
to cases of XP with severe neurological
deficiency.
Ocular problems 5 occur in nearly 80% of cases.
They include photophobia, lentigines (occur
during the first decade of life, and they might
transform into malignant melanoma), ectropion,
symblepharon with ulceration, conjunctivitis and
eyelid malignancies. Our patient had SCC
involving the right eye.
The two most common types of cancer found in
XP patients are BCC and SCC, with most
tumours found on the face, head or neck. 8,9 Early
detection of these malignancies is necessary
because they are fast-growing, metastasize early
and lead to death; most patients with XP do not
live beyond the third decade because of
development of tumours. 10,11 Kraemer et al. 5
constructed the Kaplan-Meier survival curve for
patients with XP (Box 1).
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Journal of Pakistan Association of Dermatologists 2012;22 (3):279-282.
The treatment of XP is challenging because it is
a multiorgan and multisystem disease, and
because usually by the time of diagnosis,
significant tissue damage has already occurred.
Malignant tumours may already have developed
by the third or fourth year of life. Early
diagnosis and immediate implementation of
rigorous sun protection measures may prolong
the lives of persons with XP. 12 The use of
sunscreens, other sun avoidance methods (e.g.
protective clothing, hats, eyewear) and use of
systemic retinoids have been shown to minimize
UV-induced damage and incidence of skin
cancers in patients with XP. 13 Surgical excision
of the tumours and grafting of skin from nonlight-exposed
areas is the first line of treatment.
A new approach to photoprotection is to repair
DNA damage after UV exposure by delivering a
DNA repair enzyme into the skin by means of
specially engineered liposomes. 14 T4
endonuclease V has been shown to repair
cyclobutane pyrimidine dimers resulting from
DNA damage. 15 Genetic counselling of affected
families is important. Amniocentesis may be
done for prenatal diagnosis of XP and
interruption of the pregnancy. 16
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