Xeroderma pigmentosa with ocular association: Case report

doi:10.4236/crcm.2013.28123

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Vol.2, No.8, 466-469 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.28123

Xeroderma pigmentosa with ocular association: Case

report

Achyut N. Pandey1*, Krishna Kuldeep1, Ameet a Koul1, Manoj Tyagi1, Parul Singh1,

Parmeshwari Das Sharma1, Deepak Dimri2

1Department of Ophthalmology, VCSG Government Medical College and Research Institute, Srinagar Garhwal, India;

*Corresponding Author: [email protected]

2Department of Dermatology, VCSG Government Medical College and Research Institute, Srinagar Garhwal, India

Received 13 September 2013; revised 10 October 2013; accepted 30 October 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Xeroderma pigmentosum is a rare, autosomal

recessive disease caused by a defect in DNA

repair. Patients with xeroderma pigmentosum

often have cutaneous and ocular sun sensitivity,

freckle-like skin pigmentation, multiple skin and

eye cancers, and, in some patients, progressive

neurodegeneration. Xeroderma pigmentosum

predominantly affects the ultraviolet (UV) ex-

posed ocular surface, resulting in eyelid atrophy

and cancers, corneal dryness, exposure kera-

topathy, and conjunctival tumors. General fea-

tures included parental consanguinity (40%),

familiarity (60%), onset of symptoms in the first

2 years (50%), malignant skin neoplasms (60%),

and carcinoma of the tongue (20%). Among the

ocular features, 50% of patients presented with

photophobia. Lid freckles or atrophic skin le-

sions were seen in all patients. Lower lid tu-

mours were seen in 30%, chronic conjunctival

congestion in 40%, corneal opacification in 40%,

squamous cell carcinoma of limbus in 20%, bi-

lateral pterygium in 40%, and visual impairment

in 50%. We report the clinical history and ocular

pathology of a boy who is having xeroderma

pigmentosum with ocular manifestations. The

ophthalmic manifestations of xeroderma pig-

mentosum are discussed and reviewed with re-

spect to this report and other cases in the lit-

erature. These cases illustrate the role of DNA

repair in protection of the eyes from UV damage

and neuron degeneration of the retina.

Keywords: Ciliary Body Hamartoma; Ocular

Pathology; Optic Atrophy; Xeroderma Pigmentosum;

Pigmentary Retinal Degeneration

1. INTRODUCTION

Xeroderma pigmentosum (XP), first described by

Hebra and Kaposi in 1874, presents in early childhood

with photophobia, photosensitivity, cutaneous pigmen-

tary changes, and a predisposition for malignancy in sun-

exposed mucocutaneous areas and ocular structures [1].

XP patients have a defect in DNA repair related to the

nucleotide excision repair pathway [2] or a bypass poly-

merase pathway [3]. Mutations in XPA or XPC are pre-

sent in approximately 50% of patients [4]. The disease is

extremely rare in North America and Europe (frequency

1/1,000,000) [5], but is more common in areas of the

world with increased consanguinity, including Japan

(frequency 1/22,000) [6], the Middle East, North Africa,

and India [5].

XP often presents with cutaneous manifestations

within the first two years of life [7]. Patients are pre-

disposed to malignant skin neoplasms in the face, neck

and upper trunk, the tip of the tongue, and the anterior

eye surfaces. Ocular disease is evident in at least 40%

of XP patients and often causes visual impairment.

Clinically apparent ocular disease includes eyelid atro-

phy and tumors, corneal sicca and opacification, expo-

sure keratitis, pterygium, and chronic conjunctival in-

jection. Here, we report the clinical features of a boy in

which we found classic findings of this disease and

ocular manifestations.

2. CASE

Case 1

A 6-year-old boy comes to the OPD with c/o skin le-

sions all around the body since birth. No h/o treatment

before. No h/o itching, drug use, injury. No other sibling

having the same problem. No parental consanguity. No

similar illness in the family. Birth history normal, normal

A. N. Pandey et al. / Case Reports in Clinical Medicine 2 (2013) 466-469 467

uneventful vaginal delivery. Normal growth. The chief

complaints were photophobia and defective vision.

On examination–presence of blisters all over face,

trunk, abdomen and legs (Figures 1 and 2). The lesions

are excoriating. The lesions are dry, nontender, raised

and red to pink in colour. On eye examination- both eyes

having projection of rays present and perception of light

inaccurate. The skin of the lid is excoriated. Presence of

growth in both the lids is suggesting of lid malignancy.

Conjunctiva is condested with both limbal and bulbar

conjunctival growth suggesting of basal cell carcinoma.

Cornea is totally opaque with vascularisation (Figures 3

and 4). Other details could not be made out. Neurological

examination is within normal limit. All other investiga-

tions include hemogram, lipid profile. Liver and renal

function tests, ultrasound abdomen were found to be

normal. Patient is advised for phototherapy with radia-

tion and enucleation/exanteration for ocular lesions.

Prognosis explained to parents.

Skin biopsy has been done with diagnosis of xeroder-

ma pigmentosa.

Figure 1. Face showing blisters.

Figure 2. Hand showing XP lesions.

Figure 3. Right eye.

Figure 4. Left eye.

3. LITERATURE REVIEW AND

DISCUSSION

3.1. Systemic Features and Genetics of XP

XP is an autosomal recessive disease of defective

DNA repair that affects males and females equally and is

frequently symptomatic in childhood [2]. Defects in nu-

cleotide excision repair can lead to three diseases: XP,

Cockayne syndrome, and trichothiodystrophy. XP and

Cockayne syndrome both present with photosensitivity

and progressive neurological degeneration [7]. XP has a

greatly increased risk of sun-induced cancers, and

Cockayne patients have normal cancer risk. Retinitis

pigmentosa retinopathy is well recognized in Cockayne

syndrome, while retinal abnormalities are not common in

XP patients [8]. Cockayne syndrome patients may have

poor vision with pupillary unresponsiveness, hyper-

metropia, nystagmus, hypoplastic irides, cataract, vitre-

ous floaters, optic atrophy, and global progressive pig-

mentary retinal degeneration [9]. While Cockayne syn-

drome also presents with photosensitivity and neurologic

A. N. Pandey et al. / Case Reports in Clinical Medicine 2 (2013) 466-469

468

dysfunction, patients tend to have a “bird-like” face, mi-

crocephaly, premature aging, dwarfism, cachexia, sunken

eyes, and usually die before age 30 [10]. Though the ge-

netic defects are closely related, these diseases have dif-

ferent systemic and ocular manifestations [9].

Genetic defects in XP are heterogeneous, resulting

from defects in 8 different genes (complementation

groups) [11]. Defects in nucleotide excision repair lead to

premature sunlight-induced damage including hyper-

pigmentation, hypopigmentation, lentigos, telangectasias,

actinic keratoses, and atrophy. Cutaneous symptoms usu-

ally present before 2 years of age, and the median age of

first skin neoplasm is under 10 years.

Progressive neurologic symptoms are present in about

25% of affected patients [3]. Neurologic abnormalities

include cognitive impairment, acquired microcephaly,

abnormal motor activity, areflexia, sensorineural hearing

loss, and abnormal speech. Studies suggest that neuronal

degeneration in XP is a primary process, possibly caused

by the inability to rep air DNA that has been damaged by

oxidative damage from endogenous metabolites [12].

The majority of neoplasms in patients with XP occur

in areas that are exposed to UV-radiation, including skin,

anterior surfaces of the eye, and tip of the tongue [13].

There is an increased frequency of central nervous sys-

tem tumors. Internal neoplasms may be related to envi-

ronmental carcinogen exposure that causes DNA damage,

which, like UV-damage, is poorly repaired in XP patients.

Overall, XP patients have a 70% probability of survival

to 40 years of age.

3.2 Clinical Ocular Manifestations of XP

Ocular disease is evident in at least 40% of XP pa-

tients, and blepharospasm and photophobia are common

symptoms. Eyelid skin changes reflect local skin chang es,

including usually erythema, pigmentation, atrophy, and

malignant change [14]. Telangectasias, loss of lashes,

and chronic blepharitis are also seen [14]. Atrophic

scarred skin may cause ectropion of the lower eyelid and

symblepharon [6]. Lower lid loss may result in exposure

keratitis, edema, and even corneal ulceration and perfo-

ration [15]. Corneal opacification, neovascularization,

pterygia, and band keratopathy are common, and band-

shaped nodular dystrophy and squamous cell carcinomas

have also been reported. Conjunctival involvement usu-

ally includes conjunctivitis, pinguecula, symblepharon,

melanosis, and tumors developing from the interpalpe-

bral zone of the limbus [14]. Limbal tumors, especially

pterygia, are common, and squamous cell carcinomas,

malignant melanomas and limbal stem cell deficiency

have been reported. The iris can be affected by iritis,

stromal atrophy, pigment abnormalities, and, rarely,

melanoma [16]. Orbital tumors include basal cell carci-

nomas, squamous cell carcinomas, and melanomas. As

the posterior segment is protected from UV damage by

the cornea and lens, fundus abnormalities are not com-

mon; however, choroidal melanoma rarely develops [17].

Unlike Cockayne syndrome, which is clinically associ-

ated with pigmentary retinal degeneration including

retinitis pigmentosa, retinal abnormalities have not pre-

viously been reported in XP patients.

Clinical management of XP includes avoidance of

sunlight, minimizing UV and cigarette smoke exposure,

early excision of skin lesions, and genetic counseling [3].

Oral 13-cis retinoic acid has been shown to reduce the

incidence of new cancers in XP patients [18]. Ophthal-

mic management includes UV-absorbing sunglasses with

side shields, artificial tears, intermittent topical steroids,

surveillance for ocular neoplasms, and management of

complications. Eyelid and conjunctival cancers are the

most commonly reported. Current management of eyelid

tumors is complete resection using Mohs’ micrographic

surgery, with or without reconstruction, or other tissue

sparing techniques [19]. Malignant conjunctival tumors

that can be excised should be removed and treated with

adjuvant cryotherapy/irradiation/topical chemotherapy

[20]. Some malignant limbal tumors can be removed by

iridocyclectomy, while others may require enucleation

[21]. Corneal tumors have been managed with kerato-

plasty and topical chemotherapy. Iris tumors may be

managed with local excision, plaque radiotherapy, or

enucleation [22]. Choroidal melanomas are commonly

managed with plaque radiotherapy, but this has not been

specifically studied in XP patients [23]. If a tumor in-

volves the orbit, imaging is required, and surgical exci-

sion with adjunctive radiation can be therapeutic [24].

Despite their extreme sensitivity to UV light, XP patients

can be treated with standard doses of radiation for treat-

ment of neoplasms [24]. Large or invasive ocular or or-

bital tumors may require enucleation and/or orbital ex-

enteration.

4. CONCLUSION

Patients with XP often exhibit ocular changes. Beside

the light-dependent degenerative and inflammatory

manifestations of the lids, the conjunctiva and the cornea

patients with XP also develop malignancies early in life.

The majority of patients suffer from dry eye symptoms.

XP behaved aggressively in both malignancy profile and

visual outcome. Various types of malignant ocular-cuta-

neous tumours relating to sunlight developed in

xeroderma pigmentosum patients. These disorders are

more prevalent in severe and moderate forms of

xeroderma pigmentosum. Lesions occur almost exclu-

sively in the eyelids, conjunctiva, limbus and/or cornea.

The rapid regression of these tumours, particularly in the

cornea and limbus, may cause blindness, emphasising the

importance of early management and regular monitoring

A. N. Pandey et al. / Case Reports in Clinical Medicine 2 (2013) 466-469

469

of patients in order to allow early diagnosis of this cond i-

tion, thereby ensuring the least mutilant treatment possi-

ble.

OPEN A CCESS

5. ACKNOWLEDGEMENTS

We acknowledge our patient and his family for their contributions to

our research. The author is thankful to Mr. Divyam Pandey and Anil

Semwal for help in finalising this report.

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