Case Report, Int J Ophthalmic Pathol Vol: 7 Issue: 2
Xeroderma Pigmentosum- Diagnosis and Treatment of Two Different Ocular Tumors in Eyelid and Conjunctiva
Höehr GC*, Vesanterä FR, Biselli LG, Selegatto LT, Batalha CP, Alves LP, Sobrinho MVA and Pereira IC
Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, São Paulo, Brazil
*Corresponding Author : Gabriela Chaves Höehr
Department of Ophthalmology, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, São Paulo, Brazil
Tel: +55 19 3343-7000
E-mail: [email protected]
Received: February 08, 2018 Accepted: April 18, 2018 Published: April 25, 2018
Citation: Höehr GC, Vesanterä FR, Biselli LG, Selegatto LT, Batalha CP, et al. (2018) Xeroderma Pigmentosum-Diagnosis and Treatment of Two Different Ocular Tumors in Eyelid and Conjunctiva. Int J Ophthalmic Pathol 7:2. doi: 10.4172/2324-8599.1000220
Xeroderma Pigmentosum is an autosomal recessive disease caused by alterations in the DNA repairing gene. The clinical manifestation involves extreme sensitivity to ultraviolet radiation and progressive effects in sun exposed areas (skin, mucosa and ocular surface) such as inflammation, sunburn, pigment changes and neoplasia. This disease may be associated with ocular findings such as dry eye syndrome, photophobia, blepharospasm and a number of corneal diseases such as ulceration, perforation and tumors. In this paper, we report the case of a patient with Xeroderma Pigmentosum, accompanied by ocular manifestations and treatment.
Keywords: Xeroderma pigmentosum; Ocular disease; Basal cell carcinoma; Epidermoid carcinoma
Xeroderma Pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. It is a rare autosomal recessive disorder, which is caused by a defective nucleotide excision repair system, leading to skin, ocular and neurologic alterations .
XP is a genetically heterogeneous disease which can be caused by pathogenic mutations in several genes involved in the nucleotide excision repair (NER) pathway. NER is responsible for the repair of ultraviolet-induced photoproducts within the DNA of XP patients. Eight groups of variation have been described. Males and females are similarly affected [2,3].
Clinical manifestations of classical XP include extreme sun sensitivity, skin hyperpigmentation, ocular abnormalities and an increased risk of developing neoplasms in sun-exposed areas. In a small number of cases there are neurological abnormalities and cognitive deterioration of varying severity. The first clinical manifestation normally starts at two years of age, with an unusual increased in the number of alterations in skin pigmentation in sunexposed areas and photophobia. Without sun protection, the areas become dry, rough, atrophic and can result in accelerated photo-ageing in-situ melanocyte and keratinocyte malignancy, and eventually multiple basal cell carcinomas and invasive squamous cell carcinomas and melanomas .
Recent studies indicate that about 90% of XP patients present ocular abnormalities. The ocular affections in XP can be divided into four categories: 1) ocular surface disease and inflammation, 2) corneal abnormalities, 3) structural eyelid abnormalities and 4) ocular surface and eyelid neoplasms. .
The clinical treatment of these patients includes minimizing sun exposure (avoiding direct UV radiation, using UV-absorbing sunglasses with side Shields) and avoid contact with others such as cigarette smoke. Ophthalmic management includes artificial tears, intermittent topical steroids, surveillance for ocular neoplasms, and management of complications .
Due to chronic dry eye and increased risk of lumbar deficiency, treatment studies with penetrating keratoplasty and others kind of keratoplasty do not present good results .
An 8-year-old male child diagnosed with Xeroderma Pigmentosum at two years old was referred from the Department of Dermatology to the Oculoplastic Department for evaluation of an upper right eyelid lesion with progressive growth over the previous three months. In addition, the patient had started experiencing severe eye irritation and difficulty closing his right eye approximately one month prior to evaluation. At that time, the only treatment recommended to and applied by his parents was the use of lubricating eye drops 6 times a day.
The patient had received numerous hygienic excisions of face and scalp skin lesions since 2010. In addition to actinic keratosis, 29 of the lesions were diagnosed as basal cell carcinoma and 5 were diagnosed as squamous cell carcinoma.
Inspection: Hyperpigmented spots and hyperkeratotic lesions in sun-exposed areas.
Tumor mass with bleeding to the touch which prevents ocular closure in the upper right eyelid (Figure 1).
The patient also presented cicatricial madarosis and ectopia.
Due to poor collaboration, complete eye examination was performed under anesthesia. Patient did not report visual acuity.
Refraction: Bilateral corneal opacity prevented retinoscopy.
Biomicroscopy OD: Severe conjunctival hyperemia, loss of eyelashes, scarce tear film with corneal opacity and several areas of leukoma.
Biomicroscopy OS: Conjunctival hyperemia, loss of cilia, presence of conjunctival lesion with corneal invasion and corneal walleye (Figure 2).
Fundoscopy: Impossible due to opacity.
We performed an excision of the upper right palpebral lesion and a reconstruction with cervical cutaneous graft. A left conjunctival lesion was concurrently biopsied.
Results of anatomopathological examination: The right palpebral lesion was diagnosed as solid infiltrative basal cell carcinoma (Figure 3) and the left eye lesion as epidermoid carcinoma in situ of the conjunctiva mucosa (Figure 4).
Patient evolved with excellent results from the palpebral graft (Figure 5). The occlusive capacity and the surface of the right eye also showed good improvement (Figure 6).
For the left eye, the treatment of carcinoma with Mitomycin C 0.04% eye drops for 4 cycles was chosen, with a significant improvement occurring as a result.
Unfortunately, the patient developed an extensive cutaneous ulcer tumor in the occipital region of the head, evolving into a serious infectious condition and ultimately death. Due to the clinical severity, it was not possible to conclude the ocular treatment with effectiveness.
Ocular abnormalities are frequently observed in XP patients. In a retrospective observational study, including eighty-seven patients with XP, 91% of them had at least one ocular abnormality . A review of 14 eye exams of seven XP patients under 15 years of age, showed dry eye in all the cases, ocular surface squamous neoplasia in 93%, limbal stem cell deficiency in 64.3%, conjunctival melanosis in 50%, anterior symblepharon in 21.4%, pseudopterygium in 14.3%, inflammatory granulomatous conjunctivitis in 7.1% and 42.9% had histopathological features of invasive squamous cell carcinoma .
In a study with XPA-deficient mices exposed to low daily doses of UV-B radiation, they all presented ocular surface damage, red eye, photophobia, corneal opacity and squamous cell carcinoma formation .
It is estimated that before the age of twenty that the risk of these patients of developing skin cancer is about 10,000 times more probable than the normal population for non-melanoma skin cancer and 2,000 times more likely for melanomas .
Unfortunately, the diagnosis of ophthalmological lesions in our patient was performed too late. The patient, under dermatology care, performed only hygienic excisions of skin lesions and was only sent to our department for evaluation due to severe eyelid involvement. At that moment, the patient already presented conjuctival corneal lesions and dry eye symptoms that were neglected before.
A reconstruction with cutaneous graft was chosen to repair the palpebral lesion; obtaining excellent final results and an improvement of eyelid function. Beyond that, Mitomycin C eye drops was chosen to treat the conjunctival corneal lesion diagnosed as epidermoid carcinoma in situ .
The use of Mitomycin C has been used as an adjuvant for the treatment of intraepithelial neoplasia and corneal-conjuctival squamous cell carcinoma. The use of this medication, which acts by inhibiting DNA synthesis, has been shown to be effective not only as a primary therapy but also as a coadjuvant of the surgical treatment .
Unfortunately, due to the severity and the evolution of the condition of the disease, the patient presented skin damage that evolved to infection and necrosis of cephalic regions and death.
Attention must be paid to the importance of avoiding sun exposure, early diagnosis of the disease and multidisciplinary follow-up since childhood; all in an attempt to improve patient´s quality of life and life expectancy.
XP is a rare disease that requires multidisciplinary follow-up to avoid to the maximum the damage of tissues exposed to sun radiation and consequent growth of tumors; benign, carcinomas or even melanomas. Ocular abnormalities occur in a varied and early manner, requiring strict monitoring of the lesions for a better diagnosis and treatment.
Guidelines on protection of UV radiation using sunscreen, sunglasses, hats and proper clothing are of paramount importance for XP patients, as well as follow-ups with psychologists and genetic counseling.
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