Safe, mild ultraviolet-B exposure: An essential human requirement for vitamin D and other vital bodily parameter adequacy: A review.

The enigma of skin sunburning, skin ageing and skin cancer and essential vitamin D production both resulting from solar ultraviolet-B (280-315 nm) (UVB) exposure has long puzzled photobiologists. Advice to patients by non-photobiological clinicians is now often to sunbathe to acquire vitamin D adequacy. However, modern work shows only mild UVB exposure is needed to maintain satisfactory levels, which have been demonstrated as very similar in summer and winter from about 25° to 70° north. Even very careful high protection factor 15 sunscreen use does not prevent adequate production, although it is slightly reduced, such that obsessive use of very protective screens of 50 + might. Dark skin pigmentation too usually at most minimally impairs production. However, confinement indoors and widespread clothing cover can, but oral supplementation overcomes any such deficiency. Thus, vitamin D adequacy needs just mild regular UVB skin exposure well under sunburning levels, unlikely to cause significant skin damage. This suggests mild UVB exposure may also be needed for other bodily requirements, which is indeed so. Thus, it also prevents the development of contact dermatitis and polymorphic light eruption through suppressing adaptive immunity. It also prevents the occurrence of multiple skin infections resulting from this suppression through stimulating innate immunity and cutaneous bacterial defensin production. Finally, blood pressure is reduced through low-dose UVB-induced production of the vasodilator nitric oxide (though UVA, 315-400 nm, is more efficient). Thus, mild UVB exposure is important for several aspects of internal health, whereas high-dose exposure is extremely detrimental to cutaneous health.

Audit of the use of psoralen photochemotherapy (PUVA) and narrowband UVB phototherapy in the treatment of psoriasis.

BACKGROUND: Psoralen photochemotherapy (PUVA), the combined use of psoralen and long wave ultraviolet (UVA) irradiation, was introduced around 1974 and its beneficial effects were rapidly confirmed worldwide. In an attempt to minimize its recognized long-term photocarcinogenic risk after some 150-200 exposures while also maintaining efficacy, however, the narrowband (311-312 nm) ultraviolet B (UVB) lamp (TL-01) was introduced in 1984, and has moved towards replacing PUVA except for severe or resistant disease. AIMS: To discover whether our use of these therapies complied with established British Photodermatology Group guidelines for PUVA and guidelines formulated within our unit for narrowband UVB. METHODS: The study was retrospective over 6 months from November 2001 to April 2002, all relevant information being obtained from the patients' hospital notes. RESULTS: Thirty-one patients received PUVA (18 oral, 11 bath and two uncertain because of missing notes) and 20 narrowband UVB during this period. CONCLUSIONS: Our PUVA and narrowband UVB phototherapy guidelines were shown to have been followed relatively closely with the following exceptions: one PUVA patient received a high cumulative exposure by mutual agreement because there was no other suitable therapy; a failure to measure minimal phototoxic doses (MPDs) in some PUVA patients; and slightly prolonged referral delays, but generally by patient choice.

Erythema multiforme following polymorphic light eruption: a report of two cases.

We report two patients in whom episodes of polymorphic light eruption were followed by recurrent erythema multiforme on exposed and nonexposed sites. Treating the polymorphic light eruption with prophylactic PUVA and/or oral prednisolone or cyclosporin prevented the development of erythema multiforme, suggesting that the two events are related. It is possible that erythema multiforme develops as a response to the same causative antigen as polymorphic light eruption.

Topical pseudocatalase mousse and narrowband UVB phototherapy is not effective for vitiligo: an open, single-centre study.

We report an open single-centre trial to assess the efficacy of topical pseudocatalase mousse applied twice daily to the hands and face of vitiligo patients, in combination with twice-weekly suberythemogenic narrowband UVB phototherapy. The regime was generally safe and well tolerated, although several patients experienced mild transient skin rashes in association with application of the mousse and one patient suffered severe pruritus. The primary efficacy variable was the percentage change in area affected by vitiligo as assessed by digital interpretation of standardized photographs of the face and hands. There was no clear evidence of the efficacy of the regime and in fact a slight tendency overall to worsening of the patients' vitiligo.

Psoralen photochemotherapy (PUVA) is only moderately effective in widespread vitiligo: a 10-year retrospective study.

A 10-year retrospective analysis of the use of psoralen photochemotherapy (PUVA) in the treatment of vitiligo was undertaken at the St John's Institute of Dermatology, London, UK. Of 97 patients included in this study, eight had complete or almost complete repigmentation, 59 moderate to extensive repigmentation, and 30 showed little or no response. However, 24 of those who had responded to PUVA with extensive repigmentation did not consider their response satisfactory because of persistence of vitiligo at cosmetically sensitive sites, and poorly matching, speckled repigmentation. Fifty-seven patients who initially improved with PUVA therapy subsequently relapsed, in most cases within a year of stopping treatment. Relapses in 22 patients were on the same cutaneous sites as previously affected, while vitiligo at new sites developed in 20 patients and both new and old sites were affected in a further 15 patients. Patients who retained their pigmentation after 2 years appeared to have a better chance of permanent remission. The only statistically significant prognostic indicator of relapse was patient age at the start of treatment, younger patients tending to retain their pigmentation longer than older patients. This study emphasizes the need for careful patient counselling before PUVA therapy as this treatment seldom achieves extensive repigmentation that is cosmetically acceptable, and treatment response is often followed by relapse.

Ultraviolet therapy in lupus.

This review examines the use of ultraviolet (UV) therapy in lupus erythematosus (LE), a disorder usually associated with abnormally increased photosensitivity. In addition to the abnormal cutaneous response to ultraviolet radiation (UVR) exposure, photo-aggravation of systemic disease activity in systemic LE (SLE) may also occur. However, courses of UVR exposure may also be used in the treatment or prophylaxis of various photodermatoses, and LE now appears to be included in that group. Thus, several studies have reported apparent benefits of phototherapy in both cutaneous and systemic LE, although the underlying mechanisms remain obscure and final confirmation of such efficacy is still awaited in continuing studies.

Guidelines for topical PUVA: a report of a workshop of the British photodermatology group.

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

A complex photodermatosis: solar urticaria progressing to polymorphic light eruption.

We report an unusual case of localized solar urticaria which progressed on each occasion to polymorphic light eruption (PLE); this was initially noted following provocation by narrow band ultraviolet B (311-313 nm) phototherapy.

PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology.

Our 10-year experience with PUVA treatment for alopecia areata, partialis, totalis and universalis was retrospectively reviewed using charts and follow-up questionnaires for 70 patients at St John's Institute of Dermatology. In all cases, several previous therapies were judged to be unsatisfactory prior to starting PUVA, and many cases were already deemed clinically refractory prior to referral for PUVA. If cases of vellus hair growth are excluded, and those who lost their PUVA-induced regrowth rapidly on follow-up, the effective success rate was at best 6.3% for alopecia areata partialis, 12.5% for alopecia areata totalis and 13.3% for alopecia areata universalis. We affirm that PUVA is generally not an effective treatment for alopecia areata.

The efficacy of localized PUVA therapy for chronic hand and foot dermatoses.

The response to treatment of all patients enrolled over an 18-month period for localized oral or topical psoralen photochemotherapy (PUVA) of chronic hand and foot dermatoses was retrospectively reviewed. There were broadly similar success rates for the two groups for complete clearance: 61.5% (eight of 13 patients who completed therapy)--oral PUVA, 47.8% (11 of 23 patients who completed therapy)--topical PUVA, and for significant improvement: 23.1% (three of 13 patients)--oral PUVA, 30.4% (seven of 23 patients)--topical PUVA; there were no significant differences in response when diagnostic subgroupings of the hand dermatoses were taken into account. The mean number of treatments (22 for oral PUVA and 24 for topical), treatment durations (122 and 129 days), maximum UVA doses (11.2 and 12.3 J/cm2) and to a lesser extent cumulative UVA doses (189.3 and 237.0 J/cm2) for the therapies were similar in the two groups; adverse effects were minimal for both treatment protocols. However, at least five of the eight patients in the oral PUVA group and five of the 11 in the topical group who cleared completely relapsed after a mean 86 (range 19-245) and 174 (range 23-596) days, respectively. These findings are in broad agreement with those of previous studies. Therefore to avoid generalized photosensitivity and a higher likelihood of adverse effects with systemic therapy, as well as a possible slower relapse rate, topical therapy seems preferable.

p53 immunoreactivity in cutaneous PUVA tumors is similar to that in other non-melanoma skin neoplasms.

Expression of the p53 tumor suppressor gene product was determined in keratoses and skin cancers associated with psoralen photochemotherapy (PUVA). An immunocytochemical study was employed using CM-1 (polyclonal) and Do-1 (monoclonal) antibodies to human wild-type p53. Thirty-two cutaneous lesions and 20 perilesional PUVA-irradiated skin biopsies were examined from 7 patients, all of whom had received more than 200 PUVA treatments and/or a cumulative UVA dose of greater than 1000J/cm2 as treatment for widespread plaque psoriasis. p53 immunoreactivity was seen in 7 of 15 squamous cell carcinomas (46.7%), 5 of 8 dysplastic keratoses (62.5%) and in no basal cell carcinomas or benign keratoses. The overall prevalence of p53 immunoreactivity in 46.2% of malignant or dysplastic PUVA-associated skin tumors is similar to that previously found by our group in comparable skin tumors from the general population. Most patients with lesions showing positive p53 immunoreactivity had, however, been exposed to additional risk factors before receiving PUVA therapy. p53 gene sequencing of PUVA-associated non-melanoma skin cancer (NMSC) may clarify whether p53 mutation contributes to the development of these tumors and whether this relates to PUVA therapy or prior carcinogen exposure.

The efficacy of psoralen photochemotherapy in the treatment of aquagenic pruritus.

Psoralen photochemotherapy (PUVA) was effective in the treatment of five patients with aquagenic pruritus, associated in one with polycythaemia rubra vera and in another with the myelodysplastic syndrome. Relapse occurred within 2-24 weeks when treatment was discontinued. Maintenance therapy or a further course of PUVA was necessary to maintain remission. This requirement may limit the value of the therapy.

Photoprotection and 5-MOP photochemoprotection from UVR-induced DNA damage in humans: the role of skin type.

Sites on previously unexposed buttock skin in 18 subjects (skin types I-V) were treated daily for 2 weeks with suberythemogenic doses of solar-simulated radiation (SSR) alone, SSR plus a UVB sunscreen, and SSR plus the same sunscreen with 5-methoxypsoralen at 30 ppm. The three sites of treatment (designated SSR, SSR/S, and SSR/S/5-MOP), and a control site that received no SSR or topical treatment, were challenged with 2MED SSR 1 week after the treatment had ceased. Biopsy samples, taken within 15 min after the challenge dose, were assessed for unscheduled DNA synthesis (UDS, interpreted as a measure of DNA damage), melanin deposition, and stratum corneum thickening. Within a given skin type, when compared with controls, the significant increase in either pigmentation or stratum corneum thickening was similar for SSR and SSR/S/5-MOP. SSR/S inhibited these endpoints. Compared with controls, UDS was significantly reduced in skin types III-V by SSR and in all skin types by SSR/S/5-MOP. SSR/S elicited no effect apart from minimal reductions in skin types IV and V. Thus, the increases in pigmentation and stratum corneum thickening seen in all skin types with SSR and SSR/S/5-MOP were accompanied by reduced UDS in all skin types with SSR/S/5-MOP but only in skin types III-V with SSR. These findings suggest that, although induced pigmentation and stratum corneum thickening may account in part for the reduction of UDS, qualitative differences in induced pigmentation may exist in skin types I-II between SSR and SSR/S/5-MOP treatments. The findings can also be interpreted to indicate that SSR/S/5-MOP treatment can afford protection against DNA damage from subsequent exposure to solar ultraviolet radiation. Risk-benefit considerations on the use of sunscreens with and without 5-MOP are discussed and the conclusion is drawn that the judicious use of 5-MOP sunscreens, particularly in skin types I-II, affords an alternative option to those seeking a suntan.

Successful treatment of severe polymorphous light eruption with azathioprine.

Two patients with severe, disabling polymorphous light eruption, who were unable to tolerate photochemotherapy and who were unresponsive to alternative recognized therapies, are described. In both cases short-term treatment with azathioprine achieved a marked clinical improvement, confirmed by testing with an irradiation monochromator. This response suggests an immunological basis for polymorphous light eruption. Patients with polymorphous light eruption vary considerably with regard to degree of photosensitivity, and while azathioprine therapy should not be considered in the majority of sufferers, we have shown that it can be very helpful in rare patients with exceptionally severe disease.

A modified dosage schedule for increased efficiency in PUVA treatment of psoriasis.

Ten patients with chronic widespread plaque psoriasis, all of whom had previously completely cleared and suffered a subsequent widespread relapse after conventional PUVA therapy, were treated with a modified UVA dosage schedule, with psoralen formulation and dosage unchanged. Initial and incremental UVA doses were maximized to near-erythemogenic levels as determined by weekly testing for minimal phototoxic dose (MPD), treatment being given three times a week. A comparison of complete psoriasis clearing between the modified treatment and the last PUVA course showed a geometric mean reduction in treatment duration of 55% (P less than 0.001) for a similar number of treatments each week, and a cumulative UVA dose of 31% (P less than 0.05), representing a reduction in treatment duration from 9.1 to 4.1 weeks and cumulative UVA dose reduction of 100.8 to 69.9 J/cm2. Such an improvement in efficiency permits a marked increase in treated patient numbers for the same cost, and is more convenient. The reduction in the total cumulative UVA dose given as larger individual doses also seems likely to lead to a lower incidence of cutaneous long-term, especially carcinogenic, adverse effects.