Uxua Floristan

Pigmentation-related genes and their implication in malignant melanoma susceptibility

Abstract:  Human pigmentation appears to be one of the main modulators of individual risk of developing malignant melanoma (MM). A large number of genes are known to be involved in rare pigmentary disorders and explain most of the variation in pigmentation phenotypes seen in human populations. This Spanish case–control study included 205 patients with melanoma and 245 control subjects. Thirty‐one single nucleotide polymorphisms (SNPs) in genes that had been mainly associated with congenital pigmentation syndromes (ADTB3A, ATRN, CHS1, EDNRB, HPS, KIT, MGRN1, MITF, MLANA, MYO5A, MYO7A, OA1, OCA2, PAX3 and SOX10) were selected. We found that the variant allele of OCA2 R419Q (rs1800407) was associated with increased risk of MM (OR 1.55, 95% CI 1.04–2.31, P = 0.03). This effect on melanoma risk appeared to be stronger among individuals with solar lentigines, or at least 50 nevi. We also describe, for the first time, an association with the variant S1666C (rs2276288) in the MYO7A gene (OR 1.35; 95% CI 1.04–1.76; P = 0.03). Again, this association appeared to be stronger in several phenotypic groups such as individuals with fair skin and those with childhood sunburns. We also found that several variants in the pigmentation genes considered were associated with intermediate phenotypic characteristics. Our findings highlight the potential importance of pigmentation genes in sporadic MM susceptibility.

Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2

Please cite this paper as: Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental Dermatology 2010; 19: 836–844.

Recalcitrant palmoplantar pustular psoriasis treated with etanercept.

Abstract:  We report a 10‐year‐old boy presenting with palmoplantar pustular psoriasis, resistant to topical and systemic treatments, who was successfully treated with subcutaneous etanercept (0.4 mg/kg) twice a week for 1 month. Maintenance therapy was extended for 18 months in combination with near ultraviolet light therapy without any adverse effect. Etanercept may be a safe and effective alternative for severe palmoplantar pustular psoriasis in children.

Diffuse Melanosis and Ascites due to Metastatic Malignant Melanoma

We present a female patient who developed mucosal and skin hyperpigmentation due to metastatic malignant melanoma. Diffuse cutaneus melanosis is a rare entity that complicates a small percentage of metastatic melanomas, confering a fatal prognosis. We discuss briefly the current evidence on pathogenesis of melanosis arising from metastatic melanoma.

Targetoid lesions and neutrophilic dermatosis within neonatal lupus erythematosus: unusual clinical and histologic presentations.

A 20-day-old female Chinese infant, without any remarkable familial or personal medical history, was brought to the emergency service with skin lesions that seemed to be nonpruriginous. The girl was otherwise well. She had not received any drug. The first dose of hepatitis B vaccination was administered within the first 24 hours of life. Mucocutaneous examination revealed a number of circular erythematosus papules and plaques distributed over the face (Figure 1), buttocks, and soles. These skin lesions had a targetoid appearance with three concentric components. Mucosal lesions were absent. Clinically, this eruption resembled congenital syphilis or erythema multiforme (presumably related to the vaccination). The skin biopsy from a targetoid lesion showed a diffuse dermal neutrophilic infiltrate with leukocytoclastic debris and edema in the papillary dermis (Figure 2). There was no evidence of leukocytoclastic vasculitis. These histologic findings were most suggestive of a neutrophilic dermatosis, chiefly, Sweet syndrome. Nevertheless, the dermoepidermal junction also showed numerous neutrophils, as well as vacuolar alteration and isolated necrotic keratinocytes, all consistent with the diagnosis of systemic lupus erythematosus. An alcian blue stain demonstrated the presence of abundant mucin within the reticular dermis. At this moment, we were very confused. Although the histologic findings were suggestive of lupus, the large number of interstitial neutrophils and leukocytoclasia were unusual. It is necessary to bear in mind that histopathologic findings of neonatal lupus erythematosus (NLE) are usually identical to those described in adult subacute cutaneous lupus erythematosus (SCLE): epidermal atrophy and a relatively sparse superficial lymphocytic infiltrate. Serologic studies were commenced, and the diagnosis of NLE was confirmed, with both the infant and mother possessing elevated anti-Ro/SSA and anti-La/SSB antibodies. An in-depth examination began, revealing no evidence of cardiac, hepatic, or hematologic abnormalities. Strict sun avoidance and 1% hydrocortisone ointment were recommended. At her 1-month follow-up visit, the skin lesions had resolved without residual pigmentation or scarring. NLE is a rare disease, with most mothers not carrying a diagnosis of connective tissue disease prior to delivery. The cutaneous eruption, which can occur at birth or within the first weeks of life, appears in a photodistributed pattern, affecting predominantly the face (the character-

Human β-defensins (HBD1 and HBD3) and malignant melanoma susceptibility

et al. Therapy related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Leukemia 2005; 19:1919–1928. 11 Rund D, Azar I, Shperling O. A mutation in the promoter of the multidrug resistance gene (MDRI) in human hematological malignancies may contribute to the pathogenesis of resistant disease. Adv Exp Med Biol 1999; 457:71–75. 12 Shali W, Helias C, Fohrer C, Struski S, Gervais C, Falkenrodt A, et al. Cytogenetic studies of a series of 43 consecutive secondary myelodysplastic syndromes/acute myeloid leukemias: conventional cytogenetics, FISH and multiplex FISH. Cancer Gen and Cytogen 2006; 186:133–145. 13 Noronha V, Berliner N, Ballen K, Lacy J, Kracher J, Baehring J, et al. Treatment-related myelodysplasia/AML in a patient with history of breast cancer and an oligodendroglioma treated with temozolomide: case study and review of the literature. Neuro Oncol 2006; 8:280–283. 14 Su Y, Chang M, Chiang M, Hsieh R. Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma. J Neuro Oncol 2005; 17:315–318.

Perianal Papules in a Child

The patient was a 10-year-old boy with no past history of interest, who was seen for a 2½-month history of perianal lesions and daily diurnal and nocturnal encopresis. After the condition developed, the child had become more withdrawn. The lesions had been seen previously in another center, being diagnosed as viral warts. The abdomen was slightly distended, soft, nontender, and dull to percussion, and feces were palpable in the colon throughout its length. The tone of the anal sphincter was reduced and the rectum was full of soft feces. In the perianal region there were 5 or 6 extremely macerated, hemispheric, skin-colored papules of about 4 mm in diameter, some of which were pediculated (Figure 1). Additional Tests Complete blood count and coagulation studies were normal. Colonoscopy demonstrated the presence of soft green feces in the rectum and sigma and an increase in the diameter of the colon throughout its length. The mucosa had a normal appearance, color, and vascularization. Histopathology The epidermis was hyperplastic, with hypergranulosis and compact orthokeratotic hyperkeratosis, and there was a lymphocytic infiltrate in the dermis (Figure 2). Studies using the polymerase chain reaction (PCR) did not identify any subtypes of the human papillomavirus (HPV). Documento descargado de http://www.actasdermo.org el 10/04/2017. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.