Treatment of localized mycosis fungoides with digital UV photochemotherapy.

BACKGROUND/PURPOSE: Photochemochemotherapy with 8-methoxypsoralen and UV-A light (PUVA) is a well-established treatment for mycosis fungoides (MF), although evidence for this therapy by means of prospective studies is scarce. However, long-term risks of PUVA are premature skin aging and development of nonmelanoma skin cancer. We therefore evaluated a device for targeted UV therapy, which reduces irradiation of unaffected skin in MF patients. METHODS: Ten patients with patch- or plaque-type MF affecting less than 10% body surface area were included in a prospective study. A total of 14 lesions were treated with cream PUVA using the digital phototherapy device skintrek(®) PT3. RESULTS: Seven of ten patients showed response to treatment. Complete clinical remission was achieved in four of ten patients (complete remission of seven of fourteen treated lesions) after an average of 13.4 weeks and an average cumulative UV dose of 42.6 J/cm(2) in a mean of 31.2 treatment sessions. Adverse events were rare and of mild severity. CONCLUSIONS: This study is the first prospective trial demonstrating efficacy and safety of cream PUVA in MF patients. As healthy adjacent skin remains unaffected, the potential to reduce the carcinogenic risk of PUVA treatment makes this new method a promising therapeutic option for localized MF.

Minimal phototoxic dose (MPD) measurements for topical photochemotherapy using a semiautomated MPD tester.

BACKGROUND: The traditional method of assessing minimal phototoxic dose (MPD) prior to photochemotherapy with psoralen-ultraviolet A (PUVA) is inconvenient and cannot directly determine PUVA start doses. A handheld minimal erythema dose UVB tester can be modified by fitting a TL-10 UVA compact fluorescence lamp (CFL). OBJECTIVES: To determine whether MPD testing is possible with a CFL and to calculate a fixed factor to convert observed MPD to PUVA-equivalent MPD. METHODS: Patients had two sets of MPD tests performed on symmetrical, contralateral sites on the lower back. MPD test results from a panel of PUVA lamps were compared with MPD from the modified handheld tester. Additionally, a questionnaire survey was completed by 43 U.K. phototherapy units to assess routine practice concerning MPD testing prior to PUVA therapy. RESULTS: Thirty-seven patients with psoriasis were recruited. Boston phototypes in the 31 with conclusive MPD reactions were: I, four; II, 11; III, 12; and IV, four. The handheld MPD results were linearly related to the PUVA panel MPD results as follows: PUVA MPD = 0·48 × handheld MPD + 0·17 J cm(-2). The measured PUVA MPD was 0·48 of the handheld MPD, not 0·15 as predicted by the published PUVA action spectrum. CONCLUSIONS: The modified MPD tester is a convenient and safe method for PUVA MPD testing, overcoming many problems of the 'traditional method'. The difference between the PUVA and TL-10 lamps was lower than predicted from published studies. This suggests that formal re-evaluation of the erythema action spectrum for PUVA is now needed.

Photo(chemo)therapy for vitiligo.

Vitiligo is a common skin disease characterized by loss of normal melanin pigments in the skin and its pathogenesis is still unclear. Treatment modalities include psoralen plus ultraviolet A, narrow-band ultraviolet B (NB UVB) phototherapy, topical and systemic steroids, topical calcineurin inhibitors, topical vitamin D analogues in monotherapy or in association with phototherapy, and surgical treatment. NB UVB (310-315 nm) radiation is now considered as the 'gold standard' for the treatment of diffuse vitiligo, and treatment with two recently introduced UVB sources that emit 308 nm wavelengths, the 308 nm xenon chloride (XeCl) excimer laser and the 308 nm XeCl excimer light, has also been reported to be effective and might be the treatment of choice for localized disease: this treatment modality has been defined as 'targeted phototherapy.'

The contribution of medical physics to the development of psoralen photochemotherapy (PUVA) in the UK: a personal reminiscence.

Psoralen photochemotherapy (PUVA) is the combined treatment of skin disorders with a photosensitizing drug (Psoralen) and UltraViolet A radiation. The introduction of PUVA therapy has arguably been the most important development in dermatology over the past 30 years and from the first days of the treatment being introduced in the UK, British medical physicists were an integral part of the effort to establish it. Medical physicists have contributed to this development in a number of ways, from designing irradiation units in the early days of the technique, through to collaborating with dermatologists in prosecuting clinical and experimental studies aimed at improving patient outcomes. That the dose of UVA radiation is administered quantitatively, and not qualitatively, has probably been the single most important contribution made by several medical physicists over this period. However, despite concerns that were expressed almost 30 years ago about the accuracy with which UVA doses are administered to patients, the medical physics community still has some way to go before we can be satisfied that statements about UVA irradiance and dose can be made with confidence.

Guidelines for bath PUVA, bathing suit PUVA and soak PUVA.

BACKGROUND: The aim of these guidelines is to encourage dermatologists to use bath psoralen plus ultraviolet A (PUVA), bathing suit PUVA and soak PUVA in the treatment of psoriasis vulgaris and other conditions. METHODS: Evidence was collected using searches of the PubMed, MEDLINE and COCHRANE databases using the keywords "bath PUVA," "soak PUVA," "bathing suit PUVA" and "turban PUVA." Only publications in English were reviewed. RESULTS: One hundred and thirty-eight studies were evaluated, 57 of which fulfilled the criteria for inclusion. CONCLUSIONS: Both bath PUVA and bathing suit PUVA are very effective and safe treatments for generalized stable plaque psoriasis (strength of recommendation, A). Soak PUVA is very effective in the treatment of both palmoplantar psoriasis and chronic palmoplantar eczema (strength of recommendation, A).

Present and future applications of lasers in neurosurgery.

The applications of laser in both adults and pediatric neurosurgery are being steadily refined today. For many routine tumor removals, contemporary lasers do not add to ultrasonic aspiration or suction resection. However, there are some tumors in which one CO2 laser is invaluable; brain stem astrocytomas, skull base tumors, and intraspinal tumors are examples. Similarly, in resections of spinal lipomas they are useful to vaporize lipomas from the roots. Laser welding of vessels is technically possible but has generally not been useful. Perhaps the most exciting application is a combination of laser energy transfer with stereotactic technology. The MRI can be used to visualize structural changes in cerebral tissue. We have used this technology in 40 rats with gliomas and have been able to demonstrate destruction.

Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.

OBJECTIVE: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar. DESIGN: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist. SETTING: General clinical research center of a university hospital inpatient unit. PATIENTS: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. MAIN OUTCOME MEASURES: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). RESULTS: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment. CONCLUSIONS: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.

Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: an open-label randomized controlled trial of efficacy.

OBJECTIVE: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. DESIGN: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. SETTING: Two university hospital dermatology departments in the Netherlands, specializing in hand eczema. PATIENTS: One hundred fifty-eight patients with moderate to severe chronic hand eczema (more than 1 year in duration). INTERVENTIONS: Oral PUVA using methoxsalen capsules and a simple portable commercial facial tanning unit, or hospital-administered bath PUVA with trioxsalen. MAIN OUTCOME MEASURES: The primary outcome was clinical assessment by a hand eczema score (evaluation of desquamation, erythema, vesiculation, infiltration, fissures, itch, and pain, each on a 4-point scale) after 10 weeks of treatment. The secondary outcome was hand eczema score at 8 weeks of follow-up, after completion of treatment. The tertiary outcome was travel cost and time off work. RESULTS: Both groups showed a comparable and substantial decrease in hand eczema score (meaningful clinical improvement). This decrease was maintained during the follow-up period. Patients treated with oral PUVA at home had lower travel costs and less time off work. CONCLUSIONS: Oral PUVA at home has a clinically relevant efficacy, similar to that of hospital-administered bath PUVA. This effect was maintained during an 8-week follow-up period. It resulted in lower travel costs and less time off work.

Treatment of vitiligo with UV-B radiation vs topical psoralen plus UV-A.

OBJECTIVE: To compare the efficacy and safety of 2 treatment modalities, topical psoralen plus UV-A (PUVA) with unsubstituted psoralen and 311-nm UV-B radiation, in patients with vitiligo. DESIGN: This intervention study was designed as a before-and-after trial with 2 arms, in which patients were consecutively included. PATIENTS: Male (n = 99) and female (n = 182) patients, who predominantly had skin type III, with extensive, generalized vitiligo of more than 3 months' duration. INTERVENTIONS: Two patient groups were investigated. The first group of patients was treated for 4 months with either topical PUVA (n = 28) or 311-nm UV-B radiation (n = 78). The second group of patients, treated twice weekly with 311-nm UV-B radiation, was followed up for 3 (n = 60), 6 (n = 27), 9 (n = 37), or 12 months (n = 51). RESULTS: Thirteen (46%) patients in the first group treated with topical PUVA showed repigmentation after 4 months. Fifty-two patients (67%) in the 311-nm UV-B treatment group showed repigmentation after 4 months. After 3 months, 5 patients (8%) in the second group showed more than 75% repigmentation of lesional skin compared with 32 patients (63%) after 12 months. As in other treatment modalities, the face showed good repigmentation, whereas hands and feet responded poorly. No adverse effects were encountered with treatment with narrowband UV-B radiation, contrary to those seen with topical PUVA treatment. The cumulative UV-B dose was very small compared with that of the topical PUVA treatment. CONCLUSIONS: According to our results, the treatment of patients with vitiligo with 311-nm UV-B radiation is as efficient as with topical PUVA and has fewer adverse effects.

Traceable calibration of ultraviolet meters used with broadband, extended sources.

A calibration system has been developed to provide increased accuracy in the measurement of the irradiance responsivity appropriate for UV meters used with broadband, extended sources of the type employed in phototherapy. The single wavelength responsivity of the test meter is obtained in the wavelength range 250-400 nm by intercomparison with a transfer standard meter in a narrow, monochromatic beam. Traceability to primary standard irradiance scales is provided via the National Measurement System with a best uncertainty of 7% (at 95% confidence). The effective responsivity of the test meter, when used with broadband extended sources, is calculated using the measured spectral and angular response of the meter and tabulated data on the spectral and spatial characteristics of the source radiance. The uncertainty in the effective responsivity, independent of the source variability, is estimated to be 10% (at 95% confidence). The advantages of this calibration system over existing approaches are discussed.

Recent advances in PUVA photochemotherapy and PDT for the treatment of cancer.

Since ancient times, many cultures worldwide found out independently that the topical administration of some photoactive natural products (mainly extracted from plants) followed by exposure to sunlight, might be an effective treatment of some skin diseases, thus accidently giving birth to the so-called photochemotherapy. In the attempt to resemble nature by exploiting its teaching, during the last two centuries, scientists tried to rationalize this knowledge in order to develop more effective therapeutic strategies and to understand in depth the mechanisms of action involved, expanding the potential application of this therapy to pathologies other than skin diseases, such as some types of tumors. In this paper we aim at giving an overview on results achieved to date on state-of-the-art photochemotherapy related to the treatment of cancer. The script is organized in three sections. Subsequent to a general introduction describing the origin and basic principles of photochemotherapy, the first section deals with the issue concerning the choice of the proper light sources for each type of therapeutic application, stressing the technological advances in the field (e.g. fiber optics). The second and the third sections provide an overview of the two clinically-established phototherapies to date, that is, PUVA photochemotherapy and PDT, respectively. Both sections are further subdivided into sub-paragraphs emphasizing specific relate topics such as principles and applications, employed light sources, and available data concerning anticancer activity. The third section also provides examples of non-conventional metal-based photosensitizers for PDT.

Temperatures reached inside stand-up ultraviolet treatment boxes.

Heat generated within ultraviolet treatment units can exacerbate eczema. To document the actual temperature changes within the treatment units, we measured the air temperatures in standard stand-up psoralen plus ultraviolet A (PUVA), narrowband ultraviolet B (UVB), broadband UVB, and combination UVA/UVB cabinets using a thermocouple thermometer. For the latter unit, we also measured the air temperatures with and without ventilation systems, and actual skin temperatures on individuals undergoing light treatment. The air temperatures rose significantly in all the treatment units, more so with PUVA and narrowband UVB boxes, and were highest with the ventilation systems shut off. Skin temperatures also rose significantly, but less dramatically. Ventilation is essential in maintaining comfortable temperatures within ultraviolet treatment units.