Treatment regimens, protocols, dosage, and indications for UVA1 phototherapy: Facts and controversies

Abstract

During the last three decades, ultraviolet A1 (UVA1) phototherapy has emerged as a specific phototherapeutic modality with distinct modes of action and some well established indications. Atopic dermatitis, localized scleroderma, and systemic lupus erythematosus seem to be the conditions with the best evidence regarding efficacy and safety of UVA1 phototherapy. Further indications for UVA1 include subacute prurigo, lichen sclerosus, dyshidrotic dermatitis, cutaneous T cell lymphoma, urticaria pigmentosa, and pityriasis rosea; nevertheless, there are some unknowns, uncertainties, and controversies concerning short- and long-term side effects, efficacy and dosage regimens of UVA1 phototherapy in some conditions. We describe and discuss treatment regimens, protocols, dosage, and indications for UVA1 phototherapy.

Introduction

Plewig and colleagues¹ and Muthzas and associates² were the first to report on a new device equipped with a super pressure mercury lamp that delivered selective high-dose radiation energy in the longer wavelength region of the ultraviolet A (UVA) spectrum (UVA1; 340-400 nm; Figure 1). Conventional broadband UVA fluorescent lamps have only a limited output and thus require relatively long exposure times to achieve biologically effective UVA1 doses. The UVA1 device developed by these investigators emits rather high doses in a reasonable amount of time. The rationale for developing UVA1 lamps was to reduce the adverse effects, in particular erythema (“sunburn”) by omitting the UVA2 part (320-340 nm), which is closer to the UVB range (280-320 nm).1., 2. When compared with UVA2, UVA1 is thus less erythemogenic and penetrates deeper into the skin.³ Whereas Mutzhas and associates predominantly used their device for diagnostic purposes, such as photoprovocation tests of photodermatoses and patch testing,1., 2. UVA1 was soon recognized as a beneficial phototherapeutic modality for the management of a global spectrum of conditions; nevertheless, metal halide bulb-equipped UVA1 devices are still used in generally accepted photoprovocation protocols where relatively high doses have to be applied.⁴ In addition to their clinical uses, UVA1 devices are widely used for cosmetic purposes because long lasting dark-brown skin pigmentation can be achieved with UVA1 without clinical evidence for erythema. There is increasing evidence that UVA1 is a powerful phototherapeutic option for the management of many conditions (Table 1).5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15.

Generally, there are two types of commercially available UVA1 phototherapy sources: The first are fluorescent lamps (eg, TL10R 100W, Philips, Eindhoven, the Netherlands), and the second are high-output metal halide bulbs (eg, Sellamed 4000W, Sellas Medizinische Geräte GmbH, Ennepetal, Germany). The fluorescent lamp cubicles permit low- to medium-dose UVA1 phototherapy, whereas the high-output metal halide sources allow up to 130 J/cm² to be delivered in a single dose (high dose). Although UVA1 phototherapy belongs to the most studied therapeutic UV modalities, which has been proved to be beneficial in many skin conditions, UVA1 phototherapy devices are not readily available in the United States; however, centers with UVA1 phototherapy capacity are easily identified by contacting the manufacturer or importer of the equipment.

There are significant differences in cost and output between fluorescent lamps and metal halide bulb platforms. Usually, fluorescent lamp cubicles are less expensive and have a lower output. Both platforms are capable of localized, as well as whole body treatment (Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7). Despite the high output of UVA1 metal halide bulbs, exposure time also can be considerably high because the patient usually is only exposed to one body site and has to turn around after a given time in order to expose the other site, as well. Depending on irradiance and dosage regimen, exposure times of 30 to 60 minutes are not uncommon.14., 16. Air conditioning is highly recommended for phototherapy units equipped with whole-body UVA1 devices. So-called UVA1 “cold-light” devices, which are equipped with a special infrared filter system, have previously been used by some phototherapy centers.17., 18. Principally, UVA1 sources designed for phototherapy should fulfill some technical requirements. For example, erythematogenic irradiance for wavelength λ < 340 nm must not be greater than 5% of the total erythematogenic irradiance. Wavelengths with λ < 320 nm should be negligible and infrared also should be effectively filtered out; hence, irradiance of wavelengths with λ > 800 nm < 1 mm must be smaller than 5% of the total irradiance.

There is no consistency with regard to categorization of UVA1 dosage ranges. In the United States, UVA1 phototherapy is more frequently categorized as low dose (20-40 J/cm²), medium dose (40-80 J/cm²), and high dose (80-120 J/cm²)¹⁴; however, to be consistent with papers discussed in the this contribution, we suggest the following dosage categories: low-dose UVA1 (10-20 J/cm²), medium-dose UVA1 (> 20-70 J/cm²), and high-dose UVA1 (> 70-130 J/cm²). Although many investigations have proved UVA1 to be an effective treatment modality, the optimal dosage has not been established for all indications. Dosage recommendations are detailed in Table 2 for indications, in which most clinical evidence is available for UVA1 applications.

Before starting UVA1 phototherapy, the patient's full medical history must be considered, including photo-skin type, sensitivity to sun exposure, and skin cancer history. In particular, potential phototoxic and photoallergic drugs and photodermatoses have to be excluded. Immunosuppressive drugs such as azathioprine should not be combined with UVA1.¹⁹ In a Scottish cohort, it was recently observed that the lowest median minimal erythema dose (MED) was 20 J/cm² on the back and 42 J/cm² on the arm at 8 hours for patients with photo-skin types I and II and 28 J/cm² at 8 hours on the back and 56 J/cm² at 4 hours on the arm for patients with photo-skin types III and IV.²⁰ Beattie and colleagues²⁰ suggested that daily dose regimens may risk cumulative erythema. They proposed UVA1-MED testing before starting phototherapy because of the wide range of UVA1-MEDs observed in this population. Although clinical papers and empiric observations may not indicate strong evidence for such a high risk for erythema under standard UVA1 phototherapy, particularly low and medium dose, determination of the MED should optimally be considered for patients planned to receive UVA1, in particular photo-skin types I and II. As proposed by Beattie and co-workers,²⁰ a geometric dose series of UVA1 irradiation (7, 10, 14, 20, 28, 40, 56, and 80 J/cm² for those with skin types I and II, with an additional dose of 112 J/cm², while omitting the lowest dose for those of skin types III and IV; 1.4 incremental factor) at the photoprotected lower back (8 x 1.5 cm² test areas) should be administered with readings after 8 to 24 hours postexposure. Phototherapy, particularly UVA1, has not been used as extensively in children as in adults, probably due to long-term safety concerns. Presently, there are insufficient data available to provide recommendations regarding the safe maximum dose and duration of UVA1 phototherapy in children; however, we suggest a course of low- or medium-dose UVA1 phototherapy (up to 40 sessions per year) may be justified in severe cases without therapy alternatives. These children should be monitored at least annually for early detection of photodamage or skin cancer.²¹

Regular UVA1 dosimetry is highly recommendable. Using a calibrated spectroradiometer the spectrum of the UVA1 light source can be measured. The integrated irradiance within the UVA1 range can be assessed by spectroradiometry including a calculated correction factor. The irradiance should be assessed at different locations within the treatment area whereby the mean value over these locations finally defines the averaged treatment irradiance.²² For example, the Sellamed 24000 unit may need 30 to 40 locations measured (Figure 2).