Unscheduled DNA synthesis in normal human skin after single and combined doses of V-A, UV-B and UV-A with methoxsalen (PUVA)

The aim of this study was to measure unscheduled DNA synthesis (UDS) by autoradiography in normal htiman skin (1) after high dose UV-A, (2) after low dose UV-A applied before or after erythemogenic doses of UV-B, (3) after high dose PUVA and (4) after therapeutic doses of PUVA applied before and after erythemogenic doses of UV-B. Single high dose UV-A exposure induced rougbly 60% of the amount of UDS induced by equally erythemogenic doses of UV-B. Single low dose UV-A exposure did not induce UDS, nor did it significantly alter the amount of UV-B induced UDS when combined with UV-B exposure. Single high dose PUVA did not lead to UDS and had no influence on UV-B induced UDS when combined with UV-B exposure. Our findings indicate: (1) erythemogenic doses of UV-A induce a considerable DNA excision repair; (2) low dose UV-A neither augments UV-B induced DNA repair nor does it inhibit the repair process; (3) no UDS was shown to occur after either high or therapeutic doses of PUVA. This was unexpected since psoralen-DNA monoadducts have been shown to be repairable by a mechanism similar to excision repair of pyrimidine dimers. It is therefore assumed tbat PUVA as performed for therapeutic purposes either preferentially induced interstrand crosslinks not repairable via the classical repair mechanism or the repair of monoadducts was below resolution in this study; (4) therapeutic PUVA doses apparently do not interfere with excision repair of UV-B induced DNA lesions.     

The effect of UV-A and UV-B irradiation on the skin barrier. Skin physiologic, electron microscopy and lipid biochemistry studies]

In order to gain insight into the effects of UV-irradiation on the skin barrier, functional (skin reactivity), electron microscopic and lipid-biochemical studies were performed. In three different irritation models, both UV-A-irradiated and UV-B-irradiated areas proved to be more resistant to damage than normal skin, providing evidence for improvement of barrier function after UV irradiation. Electron microscopic evaluation showed that UV-B induced a significant increase in horny cell layers, whereas after UV-A no change was detected. However, both UV-B and UV-A exposure resulted in an increase in the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions, which are believed to be the essential lipid constituents for the epidermal barrier function. These findings may explain the known beneficial effects of phototherapy in dermatoses with impaired barrier function, i.e., atopic dermatitis.     

Dermal elastosis in hairless mice after UV-B and UV-A applied simultaneously, separately or sequentially

The elastosis-inducing capacity of UV-A and UV-B was studied in the skin of hairless mice. After irradiation with UV-B and UV-A applied either simultaneously, separately or sequentially, the degree of elastosis in the dermis was microscopically evaluated. This semi-quantitative method showed no significant elastosis in the UV-A irradiated mice, and moderate elastosis in the UV-B irradiated mice. Heavy elastosis was observed when the mice were exposed sequentially to UV-B and a large dose of UV-A, but if a moderate dose of UV-A was given simultaneously with UV-B, the degree of elastosis was slightly reduced compared with the elastosis induced by UV-B alone.     

Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band ultraviolet B in patients with psoriasis

The therapeutic effectiveness of radiation from a 311 nm ultravoilet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 ( P  = 0.003), 8.2 vs. 12.0 at week 2 ( P  = 0.004), and 6.6 vs. 15.6 at week 3 ( P  = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 ( P  = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm² ( P  = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.     

Histological changes observed in the skin of patients with mycosis fungoides receiving photochemotherapy

Thirteen patients with histologically proven mycosis fungoides have had sequential biopsies performed in the course of photochemotherapy. In every case, pruritus was relieved after doses of UV-A ranging from 4–8 Jc/m². Complete clinical of clearing of lesions was observed in eleven of the thirteen patients. Despite objective and subjective clearance of lesions, persistence of a cutaneous infiltrate was observed in all biopsies carried out after commencing PUVA therapy. The quantity of infiltrate was, however, less and the epidermal component considerably reduced. Because of these observations we believe that maintenance therapy with PUVA is required in the mycosis fungoides patients and that careful follow-up is essential.     

Effect of long-wave ultraviolet light (UV-A) and medium-wave ultraviolet rays (UV-B) on human skin. Critical comparison

When discussing the effects of ultraviolet radiation on human skin, one should carefully distinguish between the long wave ultraviolet light (UV-A) and the short wave radiations (UV-B and UV-C). Ultraviolet A induces immediate pigmentation but, if high energies are applied, a permanent pigmentation is elicited. This type of ultraviolet A-induced pigmentation has been called "spontaneous" pigmentation as no erythematous reaction is necessary to induce or accelerate melanine formation. Ultraviolet B provokes erythema and consecutive pigmentation. Upon chronic exposure, ultraviolet B causes the wellknown actinic damage of the skin and even provokes carcinoma. With exposures to the sunlight (global radiation), one should be most careful. The public must be informed extensively about the dangers of excessive sunbaths. The use of artificial "suns" with spectra between 260 and 400 nm is limited as it may cause the same type of damage as the global radiation. An exact schedule for use of artificial lamps is strongly recommended. After one cycle of exposures, an interruption is necessary until the next cycle of irradiations may start. Upon continual use for tanning of the skin, artificial lamps may provoke irreversible damage of the skin. Radiation sources with emission spectra of wavelengths between 315 and 400 nm exclusively are well suited for the induction of skin pigmentation (cosmetic use). Potent radiation such as UVASUN systems provoke a "pleasant" permanent pigmentation after exposures for less than one hour. The use of ultraviolet A (UV-A) does not carry any risk for the human skin.     

Susceptibility to UV-A and UV-B provocation does not correlate with disease severity of polymorphic light eruption

OBJECTIVE: To examine whether the ease of disease provocation by UV-A and/or UV-B radiation correlates with clinical features of polymorphic light eruption (PLE), including those indicative of disease severity. DESIGN: Intervention study. PATIENTS: One hundred forty-three patients with PLE. INTERVENTIONS: Provocation testing with broadband UV-A and UV-B lamps. Additionally, a range of clinical characteristics of the disorder, including a 5-item PLE severity score, was assessed by questionnaire. MAIN OUTCOME MEASURES: Percentage of PLE rash induction by UV-A and UV-B provocation, differences between the skin types, and correlation between the results of provocation and a range of clinical characteristics of the disorder, including a 5-item PLE severity score. RESULTS: Rash provocation was seen in 78.3% of patients after UV-A and in 46.7% after UV-B exposure. Neither UV-A nor UV-B provocation showed a significant association with the total 5-item severity score. The UV-B reactivity was associated with a high score on the severity item "number of months affected per year" (P = .04), whereas UV-A responsiveness showed a tendency for association with facial involvement (P = .06). CONCLUSION: The objective assessment of UV-A or UV-B susceptibility in this large group of patients showed no significant relationship with clinical disease severity.     

Histological skin changes in heterozygote carriers of mutations in ABCC6, the gene causing pseudoxanthoma elasticum

BACKGROUND: Pseudoxanthoma elasticum (PXE) is related to mutations in the ABCC6 gene and characterized pathologically by dystrophic and mineralized elastic fibres. Heterozygote carriers of ABCC6 mutations may have a limited PXE phenotype. OBJECTIVE: To compare histological changes in the skin of genotyped siblings from two PXE pedigrees. METHODS: Mutation analysis of ABCC6 was performed. Skin biopsy samples were stained (orcein) and immunolabelled for elastin, and for vitronectin and bone sialoprotein, which are partially responsible for the mineralization within the elastorrhexic fibres. Results In all individuals mutation analysis of ABCC6 allowed definition of the genotype status, i.e. PXE (n = 2), heterozygote (n = 7) or wild type (n = 2). The study identified three histological phenotypes related to the ABCC6 genotype in siblings from both families. Heterozygote carriers had changes in dermal elastic fibre organization, morphology and labelling midway between those seen in PXE skin and normal skin. CONCLUSION: Even though the number of individuals studied here is small and precludes any hasty generalization, having a single mutation in the ABCC6 gene seems enough to modify dermal elastic fibres. The relevance of performing a skin biopsy to identify heterozygote carriers in the family of a PXE patient remains to be determined.     

Natural UV-B radiation received by people with outdoor, indoor, and mixed occupations and UV-B treatment of psoriasis

Measurements have been made of the biologically-effective environmental UV-B radiation [UV-B(BE)] received by people in different occupations in Sweden. These UV-B(BE) doses have been compared with those received from artificial UV-B radiation by patients undergoing phototherapy for psoriasis. The results indicate that for patients with outdoor occupations the therapeutic dose contributes something like one third of their total UV-B(BE) presumably only to the hands and face. For patients who work indoors, however, the therapeutic dose can be anything from 50%to almost 100% of their total UV-B(BE) burden.     

Histologic changes produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the skin of mice carrying mutations that affect the integument

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces epidermal hyperplasia and hyperkeratosis, squamous metaplasia of the sebaceous gland, and keratinized cyst formation in 8 strains of mice with the recessive mutation, hairless (hr/hr). The extent of these histologic changes is dependent on the genetic background. No cutaneous lesions are produced in haired (hr/+) mice. In examination of mice with 7 other mutations affecting the integument, TCDD produced similar histologic skin changes in cryptothrix, nude, plucked, and atrichosis; a marginal squamous metaplasia of sebaceous glands in Repeated epilation, and had no effect in fur deficient and Naked mutants. These genetically determined epidermal responses are discussed in light of the mechanism of action of TCDD.     

Histological findings in clinically normal palmar skin of patients with psoriasis

Light microscopy was used to examine the clinically normal palmar skin of 18 psoriatic patients (10 inactive and 8 active) and 18 non-psoriatic control patients. Histological changes in both epidermis and dermis vary with activity of the disease. The findings support the view that defective keratin formation precedes excessive proliferation of epidermal cells.     

Histological findings in clinically normal skin of patients with insulin-dependent diabetes

Biopsies of clinically normal skin of 22 young patients with insulin-dependent diabetes of varying duration (> 10 years, n < 5 years, n= 10) were examined using a panel of histological stains, and compared with those of 10 non-diabetic control subjects of similar age. Abnormalities under light microscopy were scored for severity. Scores for both groups of diabetics were significantly greater than scores for controls (P < 0·001). Increased upper dermal vasculature and PAS posttivity of blood vessel walls were more frequent in diabetic skin than in controls, and increased with duration of disease. PAS positivity was caused in part by deposition of glyeogen in cndotheiinl cells. Clumping of elastic fibres in the upper dermis was observed in seven of the 22 skin biopsies from diabetic patients, but not in control biopsies. An inflammatory infiltrate was more frequent in diabetic skin. No association was demonstrated between the histological scores and the presence of diabetic retinopathy, or the concentration of glycosylated haemoglobin in the diabetic subjects. None of the histological features was specific to diabetic skin.     

Induction of mixed-function oxidases in mouse liver by psoralens

8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitro-anisole-O-demethylase and slightly induced aryl hydrocarbon hydroxylase. Psoralen and 4,5′,8-trimethylpsoralen failed to induce either enzyme. These results represent the first enzyme induction studies on these clinically useful compounds. The studies may have relevance in understanding the clinical differences in skin photosensitizing activity and photochemotherapeutic effectiveness of the compounds in such diseases as psoriasis and vitiligo.