Oral Vitamin D Rapidly Attenuates Inflammation from Sunburn: An Interventional Study.

The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of UVR. Compared with placebo, participants receiving vitamin D3 (200,000 international units) demonstrated reduced expression of proinflammatory mediators tumor necrosis factor-α (P = 0.04) and inducible nitric oxide synthase (P = 0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded, unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D3 levels after treatment (P = 0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (P = 0.005), and a sustained reduction in skin redness (P = 0.02), correlating with significant expression of genes related to skin barrier repair. In contrast, participants with lower serum vitamin D3 levels had significant expression of proinflammatory genes. Together the data may have broad implications for the immunotherapeutic properties of vitamin D in skin homeostasis, and implicate arginase-1 upregulation as a previously unreported mechanism by which vitamin D exerts anti-inflammatory effects in humans.

Objective determination of Fitzpatrick skin type.

The overall aim of this Ph.D. project was to clarify what the subjective Fitzpatrick skin type represents with regard to the skin's reaction to UVR. Fitzpatrick skin type is used as an expression of the constitutive UV-sensitivity. It has been used for guiding dose-levels in phototherapy and is an important risk factor for skin cancer. The subjective Fitzpatrick skin type and the measured skin type PPF (pigment protection factor, calculated based on a skin reflectance measurement, predicts the UV-dose (SED) to give 1 MED) were investigated parallelly in relation to the clinically determined dose to erythema (MED) and/or pigmentation (MMD) to determine which one related best. PPF is an established method for assessing UV-sensitivity by predicting SED to MED. UV-dose to MED and/or MMD was determined after single UV-exposure to Solar Simulator on nates (n= 84) and after single and multiple (5, 6 or 12) UV-exposures (n = 24-62) on the back to four UV-sources (nUVB, Solar, bUVA and UVA1). SED to MMD was also related to wavelength. MED was only determined after a single and four UV-exposures to narrowband UVB (nUVB) and Solar Simulator (Solar). Volunteers with a broad range of constitutive pigmentation (skin types I-V) were included. Equal MMD doses (predetermined after a single UV-exposure) were used at the multiple exposures. The absolute increase in pigmentation after 6 and 12 UV-exposures, where steady-state pigmentation was reached, was independent of skin type and therefore could not enter into the calculations. But it proved that the MMD determinations after single exposure were correct and could be used at multiple UV-exposures. In contrary to what we expected, our results indicate that people may refer to the constitutive pigmentation, when they reply to the question of Fitzpatrick skin type. This applied to both erythema and pigmentation response as both dose to MED and MMD showed a better correlation to nates than to the back. As expected, our results from the back indicate that people seem to refer to sun sensitivity after multiple exposures to the sun rather than a single sun exposure, when they reply to the question of Fitzpatrick skin type. Hence, both SED to MED and SED to MMD are better correlated to skin type after respectively 4 and 5 exposures to Solar Simulator and nUVB compared to 1 exposure. Only when tanning is preceded by erythema there is a relation between SED to MMD and skin type/PPF. Thus only after nUVB and Solar. For nUVB and Solar there was a linear relation between erythema and tanning ability with the intercept different from zero. In spite of what we expected based on the literature, the correlation was better between SED to MED and skin type than between SED to MMD and skin type. This applied to single and multiple exposures and to single calculations and multiple regression analyses. The long-waved UVA1 and broadband UVA should definitely not be used for skin type determination, as there was no relation between MMD and skin type/PPF. Both nUVB and Solar can be considered. Finally, based on the objective parameters: pre-exposure pigmentation measured by skin reflectance, MED and MMD we tried to predict the Fitzpatrick skin type by multinominal logistic regression analyses to evaluate the significance of the different parameters for the subjective skin type classification and thereby hopefully enlighten what Fitzpatrick skin type represents. For single UV-exposure only the pre-exposure pigmentation worked as a predictor of Fitzpatrick skin type, and that is what PPF is based on. When this parameter was removed, only SED to MED was significant. Our model succeeds better to classify people correct after multiple UV-exposure compared to a single UV-exposure. PPF was predicted likewise and was highly correlated to SED to MED, as expected, and even higher correlated to Fitzpatrick skin type. SED to MMD was not significant. This study confirms that Fitzpatrick skin type is an unreliable predictor of UV-sensitivity with regard to MED- and MMD test. Fitzpatrick skin type in epidemiological context (risk for skin cancer) stands for burns and ability to tan may represent "cumulative" dose. SED to MED is equivalent to burns. PPF may also indirectly represent cumulative dose--the less pigmented the skin the more UVR penetrates the epidermis and will be able to accumulate and induce skin cancer. Our results indicate that Fitzpatrick skin type predominantly is determined by the skin pigmentation and that the second most important objective parameter is SED to MED (and not SED to MMD). This explains why Fitzpatrick skin type, eventhough being an unreliable predictor of UV-sensitivity, still plays an important role in epidemiology with regard to estimation of risk of skin cancer. This study showed that PPF can predict the UV-sensitivity also with regard to the tanning ability (MMD), can be applied to multiple UV-exposures and to a broader pigmentation spectrum. PPF is preferred to predict the individual UV-sensitivity rather than the subjective Fitzpatrick skin type, confirmed for both nates and back, single as well as repetitive UV-exposures. It should therefore be considered to concentrate on skin reflectance measurements.

Estudio clínicopatológico de nevus melanocíticos en distintos grupos de edad / Clinical-pathological study of melanocytic nevi in diferent age groups

Objetivo: Conocer la frecuencia de presentación, las características clínicas y la correlación clinicopatológica de los nevus melanocíticos en distintos grupos de edad. Material y Métodos: Realizamos el estudio en 2247 lesiones melanocíticas correspondientes a 461 pacientes. En 90 individuos pudimos realizar un protocolo clínico en el que se recogían los datos sobre tipo de piel, color de ojos y pelo, hábitos de exposición solar, localización, número y características de los nevus melanocíticos y antecedentes familiares. De las 2247 lesiones estudiadas clínicamente, 593 fueron extirpadas y estudiadas histopatológicamnete. Resultados: Estudiamos 461 pacientes (68,1 por ciento mujeres y 31,9 por ciento hombres), de edades comprendidas entre 4 y 97 años (Media= 33,02 años). El tipo medio de piel fue el III (48,1 por ciento). Respecto a los hábitos de exposición solar, el 62,4 por ciento había sufrido alguna vez quemaduras solares, y un 20 por ciento se quemaba a menudo. La localización de los nevus más frecuente fue el tronco (34,5 por ciento de los nevus), la cabeza y el cuello (16,3 por ciento). El número total de nevus fue de 2247 (media=21.1 nevus y SD=20,3 nevus). Encontramos una asociación significativa del número de nevus con el sexo masculino (p<0.003), (media=24,2 nevus) y entre el tipo de piel (fototipo claro) y el número de nevus melanocíticos (p<0,05). Según la clasificación ABCD para los nevus atípicos, el 23,8 por ciento de los individuos estudiados presentaban un nevus con alguna de estas características. El estudio anatomopatológico se realizó sobre 593 nevus: nevus intradérmicos (30,5 por ciento), compuestos (26,8 por ciento) y congénitos, tanto intradérmicos como compuestos (22,6 por ciento). La correlación con la edad fue: nevus de unión en edades inferiores a 15 años, nevus compuestos entre 15 y 24 años, nevus intradérmicos a partir de los 45 (p<0.001), los nevus congénitos se diagnosticaban preferentemente en hombres menores de 24 años. Desde el punto de vista microscópico, el 11 por ciento de las lesiones eran nevus displásicos, asociándose significativamente a hombres entre 15 y 24 años (p<0,001). La correlación clinicopatológica fue del 100 por ciento en aquellos nevus que reunían todas las características clínicas atípicas (ABCD) e histopatológicas del displásico. Conclusión: El fototipo cutáneo representa la sensibilidad a la radiación solar: los tipos I y II presentan mayor número de nevus melanocítico y y riesgo de padecer melanoma, lo cual debe condicionar el comportamiento frente a la exposición solar desde la infancia. Además, los programas de prevención deberían combinar una alta sensibilidad, para extirpar los melanomas en un estadio inicial y una especificidad elevada, para extirpar el menor número de nevus comunes (AU)