Oral aminolevulinic acid induces protoporphyrin IX fluorescence in psoriatic plaques and peripheral blood cells.

Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) has been shown in previous studies to improve psoriasis. However, topical ALA-PDT may not be practical for the treatment of extensive disease. In order to overcome this limitation we have explored the potential use of oral ALA administration in psoriatic patients. Twelve patients with plaque psoriasis received a single oral ALA dose of 10, 20 or 30 mg/kg followed by measurement of protoporphyrin IX (PpIX) fluorescence in the skin and circulating blood cells. Skin PpIX levels were determined over time after ALA administration by the quantification of the 635 nm PpIX emission peak with in vivo fluorescence spectroscopy under 442 nm laser excitation. Administration of ALA at 20 and 30 mg/kg induced preferential accumulation of PpIX in psoriatic as opposed to adjacent normal skin. Peak fluorescence intensity in psoriatic and normal skin occurred between 3 and 5 h after the administration of 20 and 30 mg/kg, respectively. Ratios of up to 10 for PpIX fluorescence between psoriatic versus normal skin were obtained at the 30 mg/kg dose of ALA. Visible PpIX fluorescence was also observed on normal facial skin, and nonspecific skin photosensitivity occurred only in patients who received the 20 or 30 mg/kg doses. PpIX fluorescence intensity was measured in circulating blood cells by flow cytometry. PpIX fluorescence was higher in monocytes and neutrophils as compared to CD4+ and CD8+ T lymphocytes. PpIX levels in these cells were higher in patients who received higher ALA doses and peaked between 4 and 8 h after administration of ALA. There was only a modest increase in PpIX levels in circulating CD4+ and CD8+ T lymphocytes. In conclusion oral administration of ALA induced preferential accumulation of PpIX in psoriatic plaques as compared to adjacent normal skin suggesting that PDT with oral ALA should be further explored for the treatment of psoriasis.

Rapid near-infrared Raman spectroscopy system for real-time in vivo skin measurements.

A rapid dispersive-type near-infrared (NIR) Raman spectroscopy system and a Raman probe were developed to facilitate real-time, noninvasive, in vivo human skin measurements. Spectrograph image aberration was corrected by a parabolic-line fiber array, permitting complete CCD vertical binning, thereby yielding a 3.3-16-fold improvement in signal-to-noise ratio. Good quality in vivo cutaneous NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired in less than 1 s, which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis.

Topical photodynamic therapy with 5-aminolaevulinic acid does not induce hair regrowth in patients with extensive alopecia areata.

BACKGROUND: Photodynamic therapy (PDT) is a new modality involving the administration of a photosensitizer, or photosensitizer precursor, followed by its activation with light to generate a therapeutic effect. 5-Aminolaevulinic acid (ALA) is a photosensitizer precursor that is transformed by cells into protoporphyrin IX (PpIX), which can in turn be activated by red light. OBJECTIVES: To investigate the effect of PDT in alopecia areata (AA). METHODS: In six patients with extensive AA, topical ALA lotion at 5%, 10% and 20% as well as the vehicle lotion alone were applied separately to different scalp areas, followed 3 h later by exposure to red light at each treatment session. RESULTS: No significant hair growth was observed after 20 twice-weekly treatment sessions. A significant increase in erythema and pigmentation was observed for the three concentrations of ALA lotion vs. the vehicle, implying that a phototoxic PDT effect was achieved in the skin. In vivo fluorescence spectroscopy in one patient showed an increase in red PpIX fluorescence 3 h after ALA application followed by a decrease after light exposure. On fluorescence microscopy, bright red fluorescence was present in the epidermis and sebaceous glands, but not in the inflammatory infiltrate surrounding the hair follicle following ALA application. CONCLUSIONS: PDT was ineffective in the treatment of AA.

Broad-spectrum sunscreen use and the development of new nevi in white children: A randomized controlled trial.

CONTEXT: High nevus density is a risk factor for cutaneous malignant melanoma. Melanocytic nevi originate in childhood and are largely caused by solar exposure. OBJECTIVE: To determine whether use of broad-spectrum, high-sun protection factor (SPF) sunscreen attenuates development of nevi in white children. DESIGN: Randomized trial conducted June 1993 to May 1996. SETTING AND PARTICIPANTS: A total of 458 Vancouver, British Columbia, schoolchildren in grades 1 and 4 were randomized in 1993. After exclusion of nonwhite children and those lost to follow-up or with missing data, 309 children remained for analysis. Each child's nevi were enumerated at the start and end of the study in 1996. INTERVENTION: Parents of children randomly assigned to the treatment group (n=222) received a supply of SPF 30 broad-spectrum sunscreen with directions to apply it to exposed sites when the child was expected to be in the sun for 30 minutes or more. Children randomly assigned to the control group (n=236) received no sunscreen and were given no advice about sunscreen use. MAIN OUTCOME MEASURE: Number of new nevi acquired during the 3 years of the study, compared between treatment and control groups. RESULTS: Children in the sunscreen group developed fewer nevi than did children in the control group (median counts, 24 vs 28; P=.048). A significant interaction was detected between freckling and study group, indicating that sunscreen use was much more important for children with freckles than for children without. Modeling of the data suggests that freckled children assigned to a broad-spectrum sunscreen intervention would develop 30% to 40% fewer new nevi than freckled children assigned to the control group. CONCLUSIONS: Our data indicate that broad-spectrum sunscreens may attenuate the number of nevi in white children, especially if they have freckles. JAMA. 2000.

Treatment of refractory solar urticaria with plasma exchange.

BACKGROUND: Solar urticaria is a photodermatosis that can be very disabling for patients who are highly sensitive to light and can also be very resistant to therapy. OBJECTIVE: To correlate the results of serial phototesting in a patient with severe and refractory solar urticaria before and after treatment with plasma exchange. METHODS: Plasma exchange was performed five times over a period of 10 days. Phototesting to ultraviolet A (UVA) irradiation and visible light was performed with fluorescent ultraviolet tubes and an incandescent lamp. RESULTS: The urticaria that developed after very low light doses during baseline phototesting could not be provoked following plasma exchange. The patient is now almost symptom-free, with only occasional and transient hives more than 21 months after her last plasma exchange. CONCLUSIONS: Plasma exchange is a therapeutic modality to consider in highly light-sensitive patients when other treatments have failed.

Alopecia areata-like hair loss in C3H/HeJ mice and DEBR rats can be reversed using topical diphencyprone.

This study demonstrates the ability to treat successfully alopecia areata-like hair loss in both mouse and rat models using topical immunotherapy with diphencyprone.

Psoriatic plaques exhibit red autofluorescence that is due to protoporphyrin IX.

In evaluating the autofluorescence properties of normal and diseased skin we discovered that psoriatic plaques can emit a distinct red fluorescence when illuminated with UVA or blue light. Using a macrospectrofluorometer equipped with a 442 nm excitation laser, a sharp in vivo fluorescence emission peak around 635 nm could be demonstrated within the plaques of 34 of 75 (45%) patients with psoriasis. This peak was absent from normal appearing skin of psoriatic patients and also from the skin of 66 patients with other dermatologic diseases. A microspectrofluorometer coupled with the same excitation laser was used to obtain emission spectra of separated epidermal sheets and dermis from plaques demonstrating macroscopic red autofluorescence. An emission peak around 635 nm was observed in all three patients thus studied, but only on spectra obtained from the epidermis. Additional spectra of vertical microscopic sections of intact psoriatic skin from five other patients revealed that the peak originated from the stratum corneum. Emission spectra from other microlocations including the mid-epidermis and dermis of psoriatic and normal skin, as well as the stratum corneum of normal skin, failed to demonstrate a 635 nm peak. The excitation and emission fluorescence spectra of acid extracts of psoriatic scale from five patients were all similar to those of protoporphyrin IX in acid solution. High performance liquid chromatography identified the presence of protoporphyrin IX in the acid extracts from psoriatic scale of the same patients. We conclude that native psoriatic plaques can exhibit red autofluorescence that is due to elevated levels of protoporphyrin IX within scales.

The dynamics of laser-induced changes in human skin autofluorescence--experimental measurements and theoretical modeling.

To study the temporal dynamics of human skin autofluorescence photobleaching, we measured the autofluorescence spectral changes of skin in vivo during continuous exposure to 442 nm (He-Cd) laser light. Integral intensities were calculated for various spectral wavelength bands and plotted as a function of time. Mathematical analysis of the time function revealed a double-exponential photobleaching process: I(t) = a exp (-t/tau 1) + b exp(-t/tau 2) + c, in which tau 1 and tau 2 differed by an order of magnitude. A hypothesis for the mechanism of the double-exponential photobleaching dynamics was proposed and evaluated using Monte Carlo modeling of light propagation in the skin and autofluorescence escape from skin. By combining the fluorophore microdistributions, Monte Carlo simulation results and the variation in fluorescence decrease parameters (a, b, c, tau 1, tau 2) with increasing exposure intensities a biophysical explanation for the double-exponential photobleaching function was elucidated. The fast decrease term corresponds to laser-induced photobleaching in the stratum corneum, while the slow decrease term represents fluorophore changes in the dermis. The measured autofluorescence photobleaching dynamics can be used to determine the fractional contributions of different skin layers to the total autofluorescence signal measured in vivo.

Sunscreens. Use and misuse.

Although sunscreens are widely available and in common use, surveys show that an average of only half of the people on a beach on a given day wear sunscreens. Many people go to the beach to get or maintain a suntan, but many people also leave their skin unprotected. This article discusses the proper use of sunscreens, common misunderstandings, and how unprotected long-term exposure to the sun can effect your skin.

An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses.

BACKGROUND: Actinic keratoses are potential precursors of invasive squamous cell carcinoma; therefore, treatment is often recommended. Current topical treatments may cause considerable discomfort, pain, or skin irritation. This study was established to explore the role, if any, of topical 3% diclofenac in 2.5% hyaluronic acid gel in the management of actinic keratoses. OBSERVATIONS: An open-label study was conducted of topical 3% diclofenac in 2.5% hyaluronic acid gel applied to 1 or more actinic keratoses. Patients were instructed to apply 1.0 g of the gel twice daily for as many as 180 days. Treatment was stopped earlier than 180 days if lesions were assessed as cleared. Twenty-nine adults were treated for periods of 33 to 176 days (median, 62 days). Of the 29 subjects, 27 were reevaluated 30 days after drug therapy discontinuation. Of the 27 patients, 22 (81%) had a complete response and another 4 (15%) showed marked clinical improvement. The preparation was generally well tolerated, although in 7 patients (24%) an irritant-type contact dermatitis developed, which was confined to the treatment site. CONCLUSION: Topical 3% diclofenac in 2.5% hyaluronic acid gel may be a clinically useful topical agent for the treatment of actinic keratoses.

Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation.

The in vivo skin autofluorescence spectrum was reconstructed by Monte Carlo simulation using microscopic fluorophore distributions and intrinsic fluorescence spectra measured from excised skin tissue sections as well as employing published skin tissue optical parameters. The theoretical modeling took into account the light-tissue interactions of scattering, absorption, and regeneration of fluorescence photons. The modification of the intrinsic spectra by tissue optical properties to generate the in vivo spectrum observed at the tissue surface can be represented by a fluorescence detection efficiency function (eta) which equals the integral of the product of the excitation light distribution inside the tissue and the fluorescence escape efficiency. Comparison of the reconstructed in vivo spectrum with the measured spectra showed good agreement, outside of the blood absorption bands, suggesting that (i) the theoretical modeling, (ii) the skin optical parameters used, and (iii) the measured microscopic morphology and spectral data are consistent. The divergence which exists over the strong blood absorption wavelength band (530-600 nm) suggests that the effect of blood contents on in vivo tissue optical properties deserves further investigations.

Chemical exposures, medical history, and risk of squamous and basal cell carcinoma of the skin.

The role of non-sunlight-related risk factors for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the skin was investigated in a population-based, case-control study conducted among males in Alberta, Canada. In total, 180 SCC and 226 BCC cases and 406 randomly selected male controls, frequency matched by 5-year age groups to the cases, were interviewed by trained personnel using a standardized etiological questionnaire. Data were analyzed using conditional logistic regression techniques. After adjustment for age, skin and hair color, mother's ethnic origin, and sunlight exposure, elevated risks for SCC were seen in subjects exposed to insecticides [odds ratio (OR), highest tertile, 2.8; 95% confidence interval (CI), 1.4-5.6], herbicides (OR, highest tertile, 3.9; 95% CI, 2.2-6.9), and fungicides and seed treatments (OR, highest tertile, 2.4; 95% CI, 1.4-4.0), as well petroleum products, grease, and several other exposures. Elevated risks of BCC were seen in subjects exposed to fiberglass dust (OR, 2.0; 95% CI, 1.0-3.9) and dry cleaning agents (OR, 4.6 95% CI, 1.1-19.7). Prior nondiagnostic X-ray treatment for skin conditions increased risk of both cancers. Although solar UV radiation is known to be the major environmental exposure causing nonmelanocytic skin cancer, results of this study suggest that nonsolar factors may also be important.

Non-solar ultraviolet radiation and the risk of basal and squamous cell skin cancer.

A case-control study of non-melanocytic skin cancer was conducted among men in the province of Alberta, Canada. Two hundred and twenty-six cases of basal cell carcinoma (BCC), 180 cases of squamous cell carcinoma (SCC) and 406 age-matched controls provided information concerning skin pigmentation, occupational history, recreational activity, exposure to sunlight and sources of non-solar ultraviolet radiation (NSUVR) and other potential risk factors. Our analyses show no evidence of elevated risk for BCC or SCC among subjects exposed to various types of NSUVR. This is in opposition to studies of melanoma that have shown elevated risks for exposure to fluorescent lighting, sunlamps and sunbeds.

The epidemiology of acquired melanocytic nevi. A brief review.

Presence of large numbers of acquired melanocytic nevi is a strong risk factor for malignant melanoma in adults. A series of studies conducted over the past 10 to 15 years have shown that the lighter skin color, propensity to burn rather than to tan in the sun, and frequent episodes of childhood sunburn increase nevus prevalence in childhood and adolescence. Solar ultraviolet radiation exposure itself has been implicated in both the genesis of new nevi in children and the disappearance of nevi in older adult life.

Spectroscopic and microscopic characteristics of human skin autofluorescence emission.

To improve the understanding of human skin autofluorescence emission, the spectroscopic and microscopic characteristics of skin autofluorescence were studied using a combined fluorescence and reflectance spectroanalyzer and a fiber optic microspectrophotometer. The autofluorescence spectra of in vivo human skin were measured over a wide excitation wavelength range (350-470 nm). The excitation-emission matrices of in vivo skin were obtained. An excitation-emission maximum pair (380 nm, 470 nm) was identified. It was revealed that the most probable energy of skin autofluorescence emission photons increases monotonically and near linearly with increasing excitation photon energy. It was demonstrated that the diffuse reflectance, R, can be used as a first order approximation of the fluorescence distortion factor f to correct the measured in vivo autofluorescence spectra for the effect of tissue reabsorption and scattering. The microscopic in vitro autofluorescence properties of excised skin tissue sections were examined using 442 nm He-Cd laser light excitation as an example. It was demonstrated that the fluorophore distribution inside the skin tissue is not uniform and the shapes of the autofluorescence spectra of different anatomical skin layers vary. The result of this study confirms that the major skin fluorophores are located in the dermis and provides an excellent foundation for Monte Carlo modeling of in vivo autofluorescence measurements.

"Sunburn" freckles, café-au-lait macules, and other pigmented lesions of schoolchildren: the Vancouver Mole Study.

BACKGROUND: Relatively few studies have evaluated the prevalence of pigmented lesions in children. OBJECTIVE: We assessed the prevalence and constitutional correlates of "sunburn" freckles, café-au-lait macules, congenital nevi, and several other pigmented lesions. METHODS: Six specially trained nurses examined 1592 Vancouver schoolchildren, 6 to 18 years old, under uniform lighting conditions and counted all pigmented lesions except those on the genitals, buttocks, and breasts in girls. RESULTS: In the 1146 white children of European origin, 378 Asian children, and 68 Indo-Pakistani children, the prevalence of one or more café-au-lait macules was essentially equivalent (28%). The prevalence of Becker's nevus, nevus spilus, and congenital nevi were also similar among white and Asian children. White children of European origin had a higher prevalence of sunburn freckles than the other ethnic groups. The prevalence among children of European descent was higher in subjects with light skin color, a propensity to burn rather than tan in the sun, a history of severe or frequent sunburn, freckling, and a high count of acquired melanocytic nevi. CONCLUSIONS: For most pigmented lesions prevalence rates were similar in the three ethnic groups examined. The results also suggest that the presence of large sunburn freckles in children of European descent correlates strongly with phenotypic risk factors that have been shown to be predictive of increased melanoma risk in adulthood. Parents should be counseled to take precautions with these children early in life in regard to overexposure to sunlight.

Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC) of the skin is the most common neoplasm in white populations, and solar radiation is generally accepted to be the dominant environmental risk factor for this disease. However, little information is available on the nature of the relationship between BCC and sunlight. The purpose of this study was to evaluate the nature of the relationship between sunlight exposure, pigmentary factors, and BCC of the skin. A population-based case-control study of 226 male patients with BCC diagnosed from January 1, 1983, through December 31, 1984, and 406 randomly selected male control subjects was conducted in Alberta, Canada. The study was conducted using a standardized questionnaire, administered in person by trained interviewers. Data were analyzed using conditional logistic regression methods. RESULTS: After controlling for other host and pigmentary factors, the risk of BCC was increased in subjects with light skin color and those who freckled in childhood. A history of severe sunburn in childhood also increased risk. Subjects of southern European ethnic origin were at significantly lower risk of BCC. Surprisingly, no association was seen between mean annual cumulative summer sunlight exposure and risk of BCC. A significantly increased risk of BCC was seen in subjects with increased recreational sunlight exposure in adolescence and childhood (age, 0 to 19 years), although an inverse relationship was seen with lifetime recreation exposure. The relationship with childhood sun exposure was most pronounced among sun-sensitive subjects whose skin tended to burn rather than tan in the sun. CONCLUSIONS: The lack of association between cumulative sun exposure and BCC contradicts conventional wisdom about the cause of this tumor, and the increased risk with sun exposure at age 0 to 19 years suggests that childhood and adolescence may be critical periods for establishing adult risk for BCC.