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Xeroderma pigmentosum: report of two cases and review of the literature.

Byline: Sankha Koley, Sanjiv V. Choudhary, Soumen Choudhury, Shilpi Sharma, Tanmoy Mukherjee and Kalyan Khan

Abstract: 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.

Introduction

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 UV- induced 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.

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.

###XP group D or De Sanctis-Cacchione

Type D, IV, XPD###XPD ERCC6###19q13.2-q13.3, lOqi 1 syndrome. May be considered a subtype of

###XPD.

Type E, V, XPE###DDB2###llpl2-pll###XP group E.

Type F, VI, XPF###ERCC4###l6pl3.3-p 13.13###XP group F.

Type G, VII, XPG###RAD2 ERCC5###13q33###XP group G and COFS syndrome type 3.

###XP variant. Due to mutation in a gene that

Type V, XPV###POLH###6p2i .1-p 12###codes for a specialized DNA polymerase

###called polymerase--- (eta).

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 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 Cacchione7 helped to coin the term "De Sanctis-Cacchione syndrome" to apply to cases of XP with severe neurological deficiency.

Ocular problems5 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).

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 non- light-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

References

1. Hebra F, Kaposi M. On diseases of the skin including exanthemata. New Sydenham Soc1874;61:252-58.

2. Kaposi M. Xeroderma pigmentosum [in French]. Ann Dermatol Venereol 1883;4:29-38.

3. English JS, Swerdlow AJ. The risk of malignant melanoma, internal malignancy and mortality in xeroderma pigmentosum patients. Br J Dermatol 1987;117:457-61.

4. Gratchev A, Strein P, Utikal J, Sergij G. Molecular genetics of Xeroderma pigmentosum variant. Exp Dermatol 2003;12:529-36.

5. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol 1987;123:241-50.

6. Neisser A. Ueber das 'Xeroderma pigmentosum' (Kaposi): Lioderma essentialis cum melanosi et telangiectasia Vierteljahrschr Dermatol Syphil 1883:47-62.

7. De Sanctis C, Cacchione A. Xerodermatic idiocy. Riv Sper Freniat 1932;56:269-92.

8. Kraemer KH, Lee MM, Andrews AD, Lambert WC. The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. Arch Dermatol 1994;130:1018-21.

9. Kraemer KH. Sunlight and skin cancer: Another link revealed. Proc Natl Acad Sci 1997;94:11-4.

10. Goyal JL, Rao VA, Srinivasan R, Argomal K. Oculocutaneous manifestations in xeroderma pigmentosum. Br J Ophthalmol 1994;78:295-7.

11. Masinjila H, Arnbjornsson E. Two children with xeroderma pigmentosum developing two different types of malignancies simultaneously. Pediatr Surg Int 1998;13:299-300.

12. Leal-Khouri S, Hruza GJ, Hruza LL, Martin AG. Management of a young patient with xeroderma pigmentosum. Pediatr Dermatol 1994;11:72-5.

13. Kraemer KH, DiGiovanna JJ, Moshell AN et al. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988;318:1633-7.

14. Yarosh DB, O'Connor A, Alas L, Potten C, Wolf P. Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies. Photochem Photobiol 1999;69:136-40.

15. Yarosh D, Klein J, O'Connor A et al. Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet 2001;357:926-9.

16. Ahmed H, Hassan RY, Pindiga UH. Xeroderma pigmentosum in three consecutive siblings of a Nigerian family: Observations on oculocutaneous manifestations in black African children. Br J Ophthalmol 2001;85:110-1.
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Author:Koley, Sankha; Choudhary, Sanjiv V.; Choudhury, Soumen; Sharma, Shilpi; Mukherjee, Tanmoy; Khan, Kal
Publication:Journal of Pakistan Association of Dermatologists
Article Type:Clinical report
Geographic Code:9PAKI
Date:Sep 30, 2012
Words:1322
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