RESUMEN
The efficacy of phototherapy is based on the interaction between ultraviolet (UV) radiation and the skin. The photobiological effects thus achieved depend on the wavelengths used. Targeted use of UVA and UVB, where indicated in combination with a photosensitizer such as psoralen, provides the dermatologist with a broad armamentarium for the treatment of a multitude of skin diseases. The spectrum of indications ranges from superficial dermatitis, psoriasis, and malignancies, such as cutaneous T-cell lymphoma, to deep sclerosing conditions such as morphea. The objective of the present review is to highlight the photobiological effects of the various types of UV radiation as well as the resultant clinical indications for phototherapy.
Asunto(s)
Enfermedades de la Piel/radioterapia , Piel/efectos de la radiación , Terapia Ultravioleta/métodos , Humanos , Fototerapia/métodos , Piel/inmunología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/terapia , Rayos UltravioletaRESUMEN
Die Phototherapie nutzt die photobiologische Wirkung von ultravioletter (UV-)Strahlung auf unseren Organismus. Die verschiedenen Wellenlängen der Strahlung rufen dabei ganz unterschiedliche Effekte hervor. Der gezielte Einsatz von UV-A und UV-B, gegebenenfalls auch in Kombination mit dem Photosensibilisator Psoralen im Rahmen einer PUVA-Therapie, ermöglicht dem Dermatologen die effektive Behandlung der verschiedensten Hautkrankheiten. Das Indikationsspektrum der Phototherapie reicht von oberflächlichen Ekzemerkrankungen, Psoriasis, malignen Erkrankungen wie dem kutanen T-Zell-Lymphom, bis hin zu tief in der Dermis lokalisierten sklerosierenden Erkrankungen wie der Sklerodermie. Das Verständnis der zugrunde liegenden photobiologischen Wirkmechanismen der verschiedenen Bereiche der UV-Strahlung und die sich daraus ableitenden Indikationen für eine Phototherapie soll der folgende Artikel ermöglichen.
RESUMEN
Sporadic sebaceous gland hyperplasia (SGH) is a benign skin lesion, with a high prevalence in the general population. Although SGH has been attributed to both extrinsic and intrinsic factors, the underlying genetic changes have not yet been characterized. Recently, HRAS and KRAS mutations have been identified in sebaceous naevus, a hamartoma sharing histological characteristics with SGH. Therefore we screened 43 SGH for activating mutations in RAS genes and other oncogenes. We identified a wide spectrum of mutually exclusive activating HRAS (8/43), KRAS (11/43) and EGFR mutations (7/31) in altogether 60% of the lesions investigated. A RAS and EGFR wildtype status was found in 15 normal sebaceous glands in the head and neck area. Our findings indicate that activating HRAS, KRAS and EGFR mutations play a major role in the pathogenesis of sporadic SGH. These results support the concept that SGH is a true benign neoplasm rather than a reactive hyperplasia.
Asunto(s)
Receptores ErbB/genética , Mutación/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Enfermedades de las Glándulas Sebáceas/genética , Glándulas Sebáceas/metabolismo , Adolescente , Adulto , Biopsia , Análisis Mutacional de ADN , Femenino , Genes ras/genética , Cabeza , Humanos , Hiperplasia/genética , Inmunohistoquímica , Masculino , Persona de Mediana Edad , CuelloRESUMEN
So far sun protection meant ultraviolet (UV) protection. But there is preliminary data that beside UV radiation also visible light (VIS) and near infrared A (IRA) radiation may have harmful effects on our skin resulting in photoaging and even cancer induction. Therefore, some authors claim that modern sun protection should also include shielding against longer wavelengths such as VIS and IRA. Therefore, avoidance of sun exposure at peak times and textile sun protection are important pillars of a modern prophylactic approach. Besides, antioxidants and DNA repair enzymes may be added to topical sunscreens in order to enhance the protection before and even after sun exposure. Furthermore, there are reports raising the question about a negative impact of specific UV filters on our environment causing among other things coral bleaching. There is need for more studies elucidating the benefit of photoprotective agents against UV, VIS and IRA with the aim to be environmentally safe at the same moment.
Asunto(s)
Neoplasias Cutáneas/prevención & control , Protectores Solares/uso terapéutico , Animales , Humanos , Protectores Solares/toxicidad , Vitamina D/uso terapéuticoRESUMEN
Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.
Asunto(s)
Células Madre Multipotentes/fisiología , Nevo Pigmentado/genética , Nevo Pigmentado/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Adulto , Fosfatidilinositol 3-Quinasa Clase I , Femenino , Humanos , Mosaicismo , Nevo Sebáceo de Jadassohn/genética , Nevo Sebáceo de Jadassohn/patología , Proteína Oncogénica p21(ras)/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.