S1-Guidelines on UV phototherapy and photochemotherapy.

Known in part since antiquity, the salutary effects of sunlight again garnered increasing attention in the second half of the 19(th) century. The development of a device for ultraviolet irradiation of cutaneous tuberculosis by Finnsen at the onset of the twentieth century truly marked the beginning of modern phototherapy. In dermatology, treatment methods almost exclusively use wavelengths below the visible light range (ultraviolet light). Since the early 1970s, increasingly powerful artificial light sources have become available for UVB and UVA therapy as well as the combination of UVA and photosensitizers (photochemotherapy). High structural and procedural quality standards are an essential prerequisite for the implementation of effective as well as safe phototherapy. The following guidelines outline the current consensus of leading experts in the field of phototherapy with respect to indications, contraindications, and side effects of various treatment options available. Particular focus is also on adequate UV doses at the beginning and over the further course of treatment as well as on management of side effects.

S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.

Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und fand in der zweiten Hälfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe ausschließlich die spektralen Bereiche unterhalb des sichtbaren Lichtes (ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfähige künstliche Strahlenquellen bereit für die Therapie mit UVB, UVA und die Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe strukturelle und prozedurale Qualitätsstandards sind unabdingbare Voraussetzung für die Durchführung einer gleichermaßen wirkungsvollen wie auch sicheren Phototherapie. Die Leitlinie formuliert den aktuellen Konsens führender Experten auf dem Gebiet der Phototherapie in Bezug auf die Indikationen für die jeweiligen Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere für die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das Management von Nebenwirkungen.

Phototherapy, psoriasis, and the age of biologics.

Over 10 years have passed since the first approval of a biologic agent for the treatment of psoriasis. No one can argue that the arrival of this entirely new, highly effective class of medications has not forever changed the therapeutic landscape for psoriasis. Traditional treatments such as phototherapy, however, remain both viable and effective therapies, both as standalone treatments and in combination with biologics. In general, synergistic effects are noted for combinations utilizing phototherapy; however, the long-term impact of these combinations on skin cancer development has yet to be fully determined. Increasing financial pressures for cost-effective therapies augment the appeal of phototherapy and other traditional treatments as compared with the more costly biologics. Phototherapy also remains strong outside the realm of psoriasis, in the management of atopic dermatitis, vitiligo, and cutaneous T-cell lymphoma, among other conditions. Phototherapy will remain a cornerstone in the management of psoriasis as well as nonpsoriatic skin conditions, as its efficacy is well known, its financial cost is reasonable, it is readily compatible with other therapeutics, and its utility is historically proven.

History of phototherapy in dermatology.

Over many centuries, treatment with sunlight or "heliotherapy" was used in the treatment of skin diseases. More than 3500 years ago, ancient Egyptian and Indian healers used the ingestion of plant extracts or seeds in addition to sunlight for treating "leucoderma". Modern phototherapy began with Nobel Prize winner Niels Finsen who developed a "chemical rays" lamp with which he treated patients with skin tuberculosis. However, it took several decades until phototherapy was introduced anew into the dermatological armamentarium. It was the development of photochemotherapy (PUVA) in 1974 that marked the beginning of a huge upsurge in photodermatology. The subsequent development of high intensity UV sources with defined spectra facilitated an optimized therapy for psoriasis and led to an expansion of indications for photo(chemo)therapy also in combination with topical and systemic agents. The introduction of extracorporeal photopheresis in 1987 for cutaneous T-cell lymphoma and of topical photodynamic therapy widely expanded the therapeutic possibilities in dermato-oncology.

Effect of work-related ultraviolet exposure and ophthalmic changes in Austrian farmers: the SVB-UV study.

BACKGROUND: Epidemiological screening to examine possible ultraviolet-induced ocular changes and pathologies in Austrian farmers. METHODS: The study was performed on behalf of the Austrian farmer insurance (Sozialversicherungsanstalt der Bauern). Randomly selected farmers and office workers as controls, both at the age of 35-55 years, underwent ophthalmic screening examinations. All subjects underwent complete ophthalmic examinations by slit lamp examination and Schirmer's test 1. A survey, regarding personal habits in the sun, was also conducted. RESULTS: Three hundred and ninety-two subjects underwent ophthalmic examinations of whom 297 were farmers and 95 were controls. Due to the survey, 89.7% of the farmers claimed to protect themselves from the sun during work. From these subjects, 83.7% wear a head protection, 71.0% wear sunglasses, and 54.4% usually work in the shade. There were significant differences in lid (p = 0.021) and conjunctival pathologies (p < 0.0001) between farmers and controls. CONCLUSION: Austrian farmers are at a higher risk for developing lid and conjunctival tumours which require treatment at some point. We believe that the study group was too young to show significant differences within the lens and the posterior pole. A 5-year follow-up is planned.

Failure of short-term psoralen and ultraviolet A light maintenance treatment to prevent early relapse in patients with chronic recurring plaque-type psoriasis.

BACKGROUND: Photochemotherapy using psoralen and ultraviolet A light (PUVA) is a highly effective treatment option for patients with severe psoriasis. Maintenance treatment has been advocated to provide for sustained remission. However, only a few studies have been conducted to assess the efficacy of maintenance treatment and these have provided inconsistent results. METHODS: We performed a prospective intrapatient left-right comparison study in 34 patients with chronic relapsing plaque psoriasis. PUVA treatment for clearing was given four times weekly. After complete or near-complete clearing, all patients were placed on a halfside maintenance schedule with irradiation twice weekly and then once weekly for 4 weeks each. The psoriasis area and severity index score was determined at baseline, end of the clearing phase and at 2-monthly intervals after discontinuation of treatment. RESULTS: Using a short-term maintenance protocol, a moderate delay in relapse of psoriasis was observed in only three patients (8.8%; 95% CI: 1.8-23.6%). In the remaining patients (91.2%), maintenance treatment had no effect on the length of remission. The mean time interval until relapse without and with maintenance irradiation was 4.5 +/- 3.4 and 4.6 +/- 3.4 months, respectively. CONCLUSION: Our data indicate that short-term maintenance treatment is not effective in preventing early relapse of psoriasis and should be avoided.

Oral vs. bath PUVA using 8-methoxypsoralen for chronic palmoplantar eczema.

BACKGROUND: Both oral and bath PUVA with 8-methoxypsoralen (8-MOP) have been shown to be effective in the treatment of chronic palmoplantar eczema. However, most studies were retrospective and did not include longer follow-up periods. AIM: To compare the therapeutic efficacy, tolerability and duration of remission after oral vs. bath PUVA using 8-MOP in patients with chronic palmoplantar eczema. METHODS: Twenty-nine patients were randomly allocated to treatment with oral or bath PUVA. Treatment was given thrice weekly for a maximum of 20 weeks. The primary outcome measure was the improvement in eczema score at the end of treatment. After clearing patients were followed up until relapse or up to 40 months. RESULTS: Overall, both PUVA modalities appeared comparably effective. However, after stratifying according to eczema type, significant differences in therapeutic outcome in general as well as in response to the two regimes were found. Dyshidrotic eczema responded better to both treatments (P=0.048) and remained longer in remission than hyperkeratotic eczema. Hyperkeratotic eczema cleared significantly better with oral than with bath PUVA (P=0.03). CONCLUSION: Oral PUVA is preferable for patients with hyperkeratotic eczema and bath PUVA for patients with dyshidrotic eczema.

Medium-dose is more effective than low-dose ultraviolet A1 phototherapy for localized scleroderma as shown by 20-MHz ultrasound assessment.

BACKGROUND: Recent studies suggest that ultraviolet (UV) A1 phototherapy is an effective treatment for localized scleroderma (LS); however, the optimum UVA1 dose remains to be determined. OBJECTIVE: We sought to compare the immediate and long-term efficacy of low- versus medium-dose UVA1 phototherapy for plaque-type LS. METHODS: Three comparable plaques in 16 patients were treated with 20 J/cm2 UVA1, 70 J/cm2 UVA1, or no irradiation. In total, 30 treatments were given. Skin thickness was determined by high-frequency ultrasound examination and clinical scoring. Assessments were done at baseline, immediately after treatment, and 3, 6, and 12 months thereafter. RESULTS: Ultrasound measurement showed a significantly greater reduction of skin thickness with 70 J/cm2 than with 20 J/cm2 at all time points of the study except immediately after UVA1 treatment. The clinical score of the irradiated plaques also decreased substantially but failed to detect a significant difference between the two dose regimens. LIMITATIONS: Our results only pertain to plaque-type LS and are limited by a small sample size. CONCLUSION: Medium-dose provides for better long-term results than low-dose UVA1 in LS as shown by ultrasound assessment. With clinical scoring, no significant difference between the two UVA1 dose regimens was detected, indicating that ultrasound measurement is a more sensitive method for quantifying treatment-induced skin changes in patients with LS.

Polymorphous light eruption.

Polymorphous light eruption is the most common photodermatosis, with a prevalence of as high as 10-20% in Western Europe and in the USA. It starts during the second and third decades of life. Although not life-threatening it can severely impair the quality of life, in particular during leisure activities and in outdoors workers. Polymorphous light eruption belongs to the group of so-called idiopathic photodermatoses. This term denotes dermatoses that occur in otherwise healthy individuals from exposure to sunlight or artificial light without the intervention of an exogenous photosensitizing agent. These diseases have two factors in common: they are precipitated by ultraviolet or visible radiation; and their exact pathomechanism remains obscure but is presumably immunologic in nature.

Randomized, double-blind comparison of 1 mg/L versus 5 mg/L methoxsalen bath-PUVA therapy for chronic plaque-type psoriasis.

BACKGROUND: Bath-psoralen plus ultraviolet A (PUVA) radiation therapy is increasingly replacing oral PUVA because of its superior short- and long-term safety profile. Several investigations in recent years have led to a refinement of the bath-PUVA protocol; however, the optimal therapeutic concentration of methoxsalen in the bath water has as yet not been delineated. OBJECTIVES: The therapeutic efficacy and tolerability of bath-PUVA by using two different dilutions of methoxsalen (1 mg/L vs 5 mg/L or 0.0001% vs 0.0005%) were compared in 46 patients with chronic plaque-type psoriasis in a prospective, randomized, double-blind study. METHODS: Scores of the Psoriasis Area and Severity Index excluding psoriasis of the head (PASI(TUL)) and the Plaque Severity Index (PSI) were assessed at baseline and at biweekly intervals thereafter until (near)complete clearance or maximal improvement. In addition, methoxsalen plasma levels were determined immediately after the psoralen bath during the first week of treatment and treatment-related side effects were recorded throughout the entire study period. RESULTS: The median baseline PASI(TUL) score decreased from 11.7 (7.5-32.8) to 3.3 (0.6-1.2) (-72%) in the 1 mg/L methoxsalen group and from 10.8 (6.6-20.7) to 1.4 (03.2) (-87%) in the 5 mg/L methoxsalen group (P < .01). The median baseline PSI score decreased from 9 (6-12) to 3.1 (0.6-10) (-66%) in the 1 mg/L methoxsalen group and from 9.3 (7.3-12) to 1.6 (0-3.6) (-83%) in the 5 mg/L methoxsalen group (P < .01). The median cumulative UVA exposure dose was 25.4 (5.3-81.5) J/cm2 for 5 mg/L methoxsalen and 71.9 (20.7-587.3) J/cm2 for 1 mg/L methoxsalen (P = .001). The number of exposures (22 [11-29] vs 23 [11-34]) and treatment duration (43 [19-68] vs 44 [23-66] days) was comparable for both methoxsalen dilutions (P = .97). Median psoralen plasma levels were 0 (0-26) ng/mL after the 1 mg/L and 30 (0-64) ng/mL after the 5 mg/L methoxsalen immersion (P = .001). Mild to moderate adverse events were more common in the 5 mg/L methoxsalen group. LIMITATIONS: The conclusions of this randomized controlled study are limited by the relatively small sample size. CONCLUSIONS: Our data indicate that in bath-PUVA treatment the use of a high (5 mg/L) methoxsalen concentration is substantially more effective in clearing chronic plaque-type psoriasis than a low (1 mg/L) concentration.

Efficacy of 3 different light doses in the treatment of actinic keratosis with 5-aminolevulinic acid photodynamic therapy: a randomized, observer-blinded, intrapatient, comparison study.

BACKGROUND: Topical 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) has been established in recent years as an effective treatment for disseminated actinic keratosis (AK). As yet, however, data are lacking to define the optimal light dose for activation of ALA-induced protoporphyrin IX in AK. OBJECTIVE: In the present study our purpose was to compare the efficacy and tolerability of 3 different doses of red light for ALA-PDT of AK. METHODS: Twenty-seven patients with at least 3 clearly definable, mild or moderate AKs on the scalp or face entered the study. After occlusion for 4 hours with 20% ALA, one AK each was irradiated at random with a single dose of 70, 100, or 140 J/cm2. PDT-induced pain was assessed by the patients by means of a visual analog scale that graded pain intensity between 0 and 10. Follow-up examinations were performed 1 and 3 months after PDT. RESULTS: One month after PDT, the rate of complete remission (CR) was 89% for 70 J/cm2, 92% for 100 J/cm2, and 81% for 140 J/cm2. The CR rates at 3 months were 81% for 70 J/cm2, 77% for 100 J/cm2, and 69% for 140 J/cm2. No significant difference in therapeutic efficacy was found among the 3 light doses at either 1 month (P = .36) or 3 months (P = .96) after PDT. The degree of PDT-induced pain during irradiation was substantial and not statistically different (P = .06) for all 3 light doses. LIMITATIONS: The conclusions from this study are limited by the small sample size and only apply to topical ALA-PDT. CONCLUSION: Our results indicate that a red light dose of 70 J/cm2 may be sufficient for effective topical ALA-PDT of disseminated, mild to moderate AK on the face and scalp.

[UV-induced skin cancers]. / UV-Hauttumoren.

In this review the epidemiology and pathogenetic aspects of UV-induced malignant skin tumours (basal cell carcinoma, squamous cell carcinoma and melanoma) are discussed with regard to current literature. Whereas present knowledge, in particular, gained from experimental data, permits substantial conclusions about the development of squamous cell carcinoma, the situation for basal cell carcinoma and melanoma does not appear to be unequivocally clear. One reason for this can be explained by the fact that there exist no adequate animal models for these tumours that could exactly reflect the biological behaviour in man. Although there is no doubt about a causal role of sun exposure, this relationship is based on mere epidemiological facts.

[UV-radiation--sources, wavelength, environment]. / Ultraviolette Strahlung--Quellen, Spektren, Umwelteinflüsse.

The UV-radiation in our environment is part of the electromagnetic radiation, which emanates from the sun. It is designated as optical radiation and reaches from 290-4,000 nm on the earth's surface. According to international definitions UV irradiation is divided into short-wave UVC (200-280 nm), medium-wave UVB (280-320 nm), and long-wave UVA (320-400 nm). Solar radiation which reaches the surface of the globe at a defined geographical site and a defined time point is called global radiation. It is modified quantitatively and qualitatively while penetrating the atmosphere. Besides atmospheric conditions, like ozone layer and air pollution, geographic latitude, elevation, time of the season, time of the day, cloudiness and the influence of indirect radiation resulting from stray effects in the atmosphere and reflection from the underground play a role in modifying global radiation, which finally represents the biologically effective radiation. The radiation's distribution on the body surface varies according to sun angle and body posture. The cumulative UV exposure is mainly influenced by outdoor profession and recreational activities. The use of sun beds and phototherapeutic measures additionally may contribute to the cumulative UV dose.

UVA-induced oxidative damage and cytotoxicity depend on the mode of exposure.

The reciprocity rule (Bunsen-Roscoe law) states that a photochemical reaction is directly proportional to the total energy dose, irrespective of the dose distribution. In photomedicine the validity of this law is usually taken for granted, although the influence of radiation intensity and dose distribution are largely unknown. We have examined in a tissue culture model the effects of fractionated versus single dose exposure to UV from a metal halide source on survival, DNA synthesis, glutathione, and oxidative membrane damage. Exposure to fractionated UVA was followed by an increased rate of cell death compared to single dose exposure, when intervals between fractions where short (10-120 min). Longer intervals had the opposite effect. Corresponding results were obtained for DNA synthesis (BrdU incorporation). The increased cytotoxicity of dose fractionation with short intervals could not be abrogated by non-enzymatic antioxidants (astaxanthin, ascorbic acid, alpha-tocopherol). Fractionated irradiation with short intervals led to higher degree of depletion of glutathione (GSH) and to enhanced formation of thiobarbituric acid reactive substances (TBARS) in comparison to an identical single dose. Long intervals between fractions induced opposite effects. Taken together, these data indicate that immediately after UVA exposure cells are more sensitive to a further oxidative attack making repeated exposure with short intervals more cytotoxic than continuous single dose UVA. This might have implications also for responses to UVA in vivo and further studies will have to extend these findings to the situation in healthy and diseased human skin.

Caterpillar dermatitis in two siblings due to the larvae of Thaumetopoea processionea L, the oak processionary caterpillar.

Two siblings, 16 months and 5 years of age, came into contact with the urticating hairs (setae) of oak processionary caterpillars, the larvae of Thaumetopoea processionea L., when the family moved to a suburb of Vienna, where mass gradation of T. processionea had started the year before. The setae were being spread by the wind from an infested oak tree in the neighbourhood. Both children repeatedly suffered bouts of dermatitis during the 10 weeks of the larval development. Owing to the fact that T. processionea often infests oak trees, whether isolated or at the edges of forests, there is a high likelihood of people being affected. Children frequently explore their surroundings and are at an even greater risk of developing lepidopterism. Caterpillar dermatitis should therefore be taken into consideration in the differential diagnosis of a pruritic rash in infants from regions with caterpillar-infested trees, especially during the larval development of T. processionea .