|Year : 2018 | Volume
| Issue : 2 | Page : 107-109
Xeroderma pigmentosum complicated by keratoacanthoma in a Kashmiri girl
Yasmeen J Bhat1, Peerzada Sajad2, Najmu Saqib1, Iffat Hassan1, Roohi Wani3
1 Postgraduate Department of Dermatology, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Govt. JLNM Hospital, Government Medical College, Srinagar, Jammu and Kashmir, India
3 Postgraduate Department of Pathology, Government Medical College, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||14-Dec-2018|
Dr. Yasmeen J Bhat
Department of Dermatology, Sexually Transmitted Diseases & Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Xeroderma pigmentosum is a rare autosomal recessive genetic disorder characterized by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet radiation. It manifests clinically as intense cutaneous photosensitivity, acute burning under minimal sun exposure, erythema, xerosis, poikiloderma, actinic keratosis, lentigines, and development of malignant lesions like basal cell carcinoma, squamous cell carcinoma, and melanoma in sun-exposed areas. We hereby report a case of xeroderma pigmentosum complicated by keratoacanthoma in a 9-year-old ethnic Kashmiri girl who had history of photosensitivity, dry skin, and pigmentary changes from the age of 2 years.
Keywords: Keratoacanthoma (KA), nucleotide excision repair (NER), ultraviolet radiation (UVR), xeroderma pigmentosum (XP)
|How to cite this article:|
Bhat YJ, Sajad P, Saqib N, Hassan I, Wani R. Xeroderma pigmentosum complicated by keratoacanthoma in a Kashmiri girl. Pigment Int 2018;5:107-9
| Introduction|| |
Xeroderma pigmentosum (XP) is a hereditary autosomal recessive disorder characterized by mucocutaneous and ocular hypersensitivity to ultraviolet radiation (UVR) with irreparable DNA damage and subsequent malignant changes and in some patients also by progressive neurological degeneration., It is more common in populations where consanguineous marriages are prevalent. There is no sex or racial predilection. XP occurs in patients with molecular defects in genes involved in nucleotide excision repair (NER) of UV-induced DNA lesions. The integrity of DNA is often challenged by DNA damaging agents like UVR, affecting transcription and replication that ultimately leads to cell death, contributes to aging, and eventually leads to mutations that induce carcinogenesis. A functional NER system is the most important repair pathway for removal of UV light-induced photoproducts and DNA adducts, the significance of which is reflected from the severity of clinical features like extreme sensitivity to sun exposure, increased risk for skin cancer, and exhibition of neurological symptoms, expressed by individuals suffering from XP. The NER pathway is associated with at least 28 genes, some of which are also part of the multiprotein basal transcription factor, transcription factor II human (TFIIH), and some participate in somatic growth and development. Mutation in any of the NER genes (XPA through XPG) and the XP variant (XPV) gene leads to the disease. The proteins encoded by the XPA, −B, −C, −D, −F, and −G are required for NER and the XPV gene encodes an error-prone DNA polymerase pol eta that bypasses unrepaired DNA damage. Cells derived from persons with XP owing to XPV mutation have a normal NER pathway but have defective DNA replication after UV-induced DNA damage, the so-called DNA translesion synthesis.
| Case report|| |
A 9-year-old normotensive, non-diabetic, and euthyroid girl presented to our outpatient department with history of a small red raised lesion that had rapidly evolved over a period of 3 months. The lesion was neither associated with pain nor bleeding. The patient gave history of itching, photosensitivity, dry skin, pigmentary changes, and crusting from the early age of 2 years. There was history of first-degree consanguinity in the parents. But all other family members were normal and had no history similar to that of the child. Cutaneous examination showed dry, pigmented skin with multiple lesions of actinic keratosis, extensive freckling, and a well-defined erythematous to skin-colored sessile nodule with a central keratin-filled crater and crusting of approximately 3 × 3 cm size just over the left eyebrow [Figure 1]A and B. The lesion was nontender, firm, and mobile without any associated regional lymphadenopathy. Ophthalmologic and neurological evaluations were normal. Based on the history and examination, a differential diagnosis of keratoacanthoma complicating XP was considered. After doing baseline investigations, an excision biopsy of the nodule was taken and the diagnosis of keratoacanthoma complicating XP was confirmed by histopathological examination [Figure 2]. The histopathological examination showed epidermal hyperkeratosis, a typical crater in the epidermis filled with keratin material, epidermal hyperplasia on both sides of the edge, increased number of melanocytes in basal layer (due to underlying XP), with chronic inflammatory cell infiltrate in dermis and showing predominance of lymphocytes and eosinophils (H&E, ×100). Features suggestive of actinic damage were also noted.
|Figure 1: (A) Well-defined, erythematous to skin-colored sessile nodule with a central keratin-filled crater over the left eyebrow. (B) Extensive freckling with keratoses and keratoacanthoma over face in a young girl|
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|Figure 2: Histopathological picture of keratoacanthoma, showing epidermal hyperkeratosis, keratin-filled crater, and chronic inflammatory cell infiltrate in dermis (H&E ×100)|
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| Discussion|| |
Xeroderma pigmentosum is a group of rare genetic disorders that follow an autosomal recessive mode of inheritance, characterized clinically by extreme skin sensitivity to UV light. In homozygous affected individuals, the skin appears normal at birth but severe skin changes develop consequent to sun exposure that progress with time from the early age of 3 years. The skin changes include abnormal skin pigmentation, freckles, xerosis, telangiectasia, atrophy, and various types of keratoses. The skin changes accentuate in one or many forms with development of benign and malignant neoplasms like basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. These malignancies may develop in large numbers with increasing age. Metastatic epithelioma often causes death by 30 years of age. These skin neoplasms occur especially on sun-exposed skin. The benign tumors complicating XP include actinic keratoses, warty papillomas, keratoacanthomas, fibromas, neurofibromas, angiofibromas, and angiomyomas. In addition to these skin neoplasms, various benign and malignant neoplasias of ectodermal and mesodermal origin also develop in affected individuals with a much higher frequency than those who are not affected. Besides skin manifestations, there may be stunting of growth and poor physical development. In about 30% of individuals, progressive neurologic disease can occur in the form of ataxia and spasticity, cognitive deterioration, and abnormal hearing, reflexes, and speech. Ocular involvement occurs in the form of photophobia, conjunctivitis, ectropion, exposure keratitis leading to corneal opacification or vascularization, pterygium, and neoplasia.
Keratoacanthoma is a rapidly growing cutaneous neoplasm with the face, head, and extremities being the most common sites of predilection. This neoplasm is thought to arise from the hair follicle and is characterized by a rapid self-limiting growth and involution in about 4 to 6 months on an average. The various incriminating factors include sunlight (most common), viruses like human papilloma virus (HPV), trauma, and more recently the altered cell-mediated immunity. Morphologically, the tumor appears as a firm, nontender, well-demarcated, sessile, dome-shaped nodule with a central keratin-filled crater, which may be yellowish, brown, or black, and has an irregular, crusted often verruciform pattern. There have been a few reports of keratoacanthomas complicating XP with the mean age of occurrence being 45 years. In children, there have been only few reports of the occurrence of keratoacanthoma in XP but the exact incidence is not known. In our case, the primary lesion was in the form of a rapidly growing, firm, nontender, well-demarcated, sessile nodule with a central keratin-filled crater pointed toward a possible diagnosis of keratoacanthoma and a further diagnosis of XP (on the basis of clinical signs and symptoms). The diagnosis of keratoacanthoma was confirmed by histopathological findings. The treatment options for keratoacanthoma include complete excision, radiation therapy, intralesional injection of chemotherapeutic agents, oral retinoids, and photodynamic therapy. Recently, there are a few reports of successful treatment of keratoacanthoma with topical application of 5% imiquimod cream., However, in our case, we simply excised the lesion advised the patient for regular follow-up.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]