Targeted phototherapy

INTRODUCTION — Targeted phototherapy is the localized delivery of ultraviolet (UV) light to affected areas of skin using laser or nonlaser devices [1]. This treatment modality may be useful in some patients with psoriasis, vitiligo, and other inflammatory or lymphoproliferative skin conditions (table 1) involving a limited area of the body (<10 percent of the body surface area) or difficult-to-treat anatomical areas [2].

This topic will discuss the mechanism of action, clinical indications, treatment protocols, and side effects of targeted phototherapy. Psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and ultraviolet A1 (UVA1) phototherapy are discussed separately.

●(See "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

●(See "UVB phototherapy (broadband and narrowband)".)

●(See "UVA1 phototherapy".)

PRINCIPLES AND MECHANISMS — Targeted phototherapy can be performed with either laser or nonlaser devices that emit a spot of ultraviolet (UV) light, typically a few square centimeters. Both laser and nonlaser devices can deliver UV radiation (wavelength range 193 to 380 nm (figure 1)) that is absorbed in the epidermis and superficial dermis by skin chromophores.

The principal skin chromophore is nuclear deoxyribonucleic acid (DNA). The absorption of ultraviolet B (UVB; 290 to 320 nm) by nucleotides leads to the formation of cyclobutane pyrimidine dimers and pyrimidine (6-4)-photoproducts, which are then either repaired or marked for cell cycle arrest and apoptosis via the p53 tumor suppressor gene system [3]. UVB also acts on cytoplasm and cell membrane components (including cell surface receptors, kinases, phosphatases, and transcription factors) and induces the release of a variety of proinflammatory and immunomodulatory cytokines from keratinocytes and T cells [4].

Decreased cell proliferation, immunosuppression, and T cell apoptosis may contribute to the UVB-mediated suppression of disease activity in inflammatory and lymphoproliferative skin disorders, such as psoriasis and mycosis fungoides [5-7]. In vitiligo, UVB promotes the proliferation, differentiation, and migration of melanocytes [8]. In cutaneous mastocytosis (urticaria pigmentosa), UVB radiation reduces the release of histamine from basophils and mast cells, resulting in decreased itch and fewer urticarial lesions [9,10].

DEVICES FOR TARGETED PHOTOTHERAPY — The most common lasers used for targeted phototherapy in clinicians' offices are the excimer lasers, which operate in the ultraviolet (UV) wavelength range between 193 and 351 nm. These lasers use an active medium composed of excited dimers, which are a combination of a noble gas (eg, argon, krypton, or xenon) and a reactive halogen gas (eg, fluorine or chlorine) [11]. The 308 nm xenon-chloride laser is most commonly used to treat dermatologic conditions. Although effective, laser devices tend to be bulky and expensive. (See "Basic principles of medical lasers" and "Principles of laser and intense pulsed light for cutaneous lesions".)

Nonlaser devices can also be used to deliver localized UV to targeted lesions. They may use high-pressure burners, fluorescent bulbs, or other approaches to emit UV light and may be delivered to the skin either directly from the bulb or via fiber-optic cable systems [12]. Nonlaser excimer lamps are generally smaller, less costly, and require less maintenance than lasers [12]; some are available that can be used by patients at home and may be as effective as in-office treatment [13,14]. A nonlaser device can sometimes be filtered to provide either ultraviolet A (UVA; 330 to 380 nm) or ultraviolet B (UVB; 290 to 330 nm), which cannot be done with excimer lasers [11,15,16]. Monochromatic excimer nonlaser devices have been developed but are not yet approved by the US Food and Drug Administration for use in the United States.

CLINICAL INDICATIONS — Most common indications for targeted ultraviolet (UV) therapy include:

●Localized forms of moderate to severe psoriasis that are unresponsive to topical therapy

●Vitiligo

●Localized severe atopic dermatitis

●Alopecia areata [17]

●Lymphoproliferative skin disorders [2]

Localized phototherapy is useful for difficult-to-treat areas (scalp, palms, and soles) in patients with psoriasis [18]. In patients with vitiligo, perifollicular pigmentation on baseline dermoscopic examination may be a marker for better response to targeted phototherapy [19]. Additional indications are listed in the table (table 1).

DOSING AND TREATMENT REGIMENS — There are no widely accepted, disease-specific protocols for targeted phototherapy, due to lack of standardization among devices and limited evidence from high-quality studies. Only a few small studies have assessed the excimer laser dose-response relationship in psoriasis [20].

One approach supported by expert consensus involves determining the minimal erythema dose (MED) on normal skin prior to initial treatment. The MED is the lowest effective ultraviolet (UV) radiation dose producing erythema or "sunburn" of the skin within a few hours [21]. A dose of two to four MED can be given as the initial treatment. The dose can be increased or reduced during the course of treatment based upon response to therapy and side effects [22].

Another approach involves following the directions of the device's manufacturer for dosing. An example of protocol for a specific laser for psoriasis treatment is shown in the table (table 2).

Generally accepted treatment frequency is two to three treatment sessions per week, for a total of 10 to 20 treatments, or until the lesion is cleared [12]. Treatments should be given at least 48 hours apart [23]. For psoriasis, limited data show an average remission time of three to five months [20].

One small trial suggested that while both were effective, localized 308 nm excimer light may be more effective for vitiligo than targeted 311 nm narrowband ultraviolet B (NBUVB) [24].

COMBINATION THERAPIES — Both topical and systemic agents can be used in conjunction with targeted phototherapy with the goal of improving efficacy and reducing the radiation dose. Evidence supporting the combination of targeted phototherapy with topical or systemic agents is mainly derived from a few studies of targeted and nontargeted narrowband ultraviolet B (NBUVB) phototherapy for the treatment of psoriasis and vitiligo:

●In a small study, the combination of targeted narrowband phototherapy with topical calcipotriol was more effective than phototherapy alone or phototherapy in combination with topical psoralen gel for the treatment of localized plaque psoriasis (Psoriasis Area and Severity Index [PASI] improvement after 30 treatments was 67, 34, and 30 percent, respectively) [25]. A meta-analysis of five small, randomized trials (182 patients) confirmed that topical calcipotriene improves the efficacy of targeted phototherapy of psoriasis (mean difference of the PASI percentage change between the combined therapy versus the targeted phototherapy alone -23, 95% CI -37 to -8) [26].

●The combination of targeted phototherapy with biologics has not been well studied. In a small, retrospective study of 29 patients, the combination of biologics with 311 nm ultraviolet B (UVB) phototherapy was associated with a more rapid reduction in PASI compared with biologics alone [27]. None of the patients developed nonmelanoma skin cancer or melanoma over a median follow-up period of 234 weeks.

●A meta-analysis of two left-right intraindividual comparison studies comparing topical 0.1% tacrolimus plus 308 nm xenon-chloride excimer laser with placebo plus laser for the treatment of vitiligo demonstrated that patches treated with the combination of topical tacrolimus plus laser were more likely to achieve 75 percent repigmentation than those treated with laser alone (RR 3.15; 95% CI 1.46-6.76) [28].

●Vaseline and other emollients can increase ultraviolet (UV) penetration by altering the optical properties of the stratum corneum [29]. Although evidence-based data are scant, some experts suggest applying a thin petrolatum layer just prior to UV treatment.

TARGETED VERSUS FULL-BODY PHOTOTHERAPY

Advantages — Advantages of targeted phototherapy include less toxicity to normal skin, fewer treatments, and a lower cumulative ultraviolet (UV) dose compared with whole-body phototherapy [30]:

●Targeted therapy delivers a higher amount of radiation in a shorter period of time only to the individual lesions, avoiding unnecessary exposure to UV of the unaffected skin. This minimizes short- and long-term adverse effects of UV radiation exposure, such as sunburn and skin cancer. If burns do occur, they tend to be better tolerated, since they are limited to the lesions.

●Because diseased skin often tolerates larger UV doses than normal skin, the initial treatments can use higher UV doses, resulting in a lower number of treatment sessions needed to achieve a response. Treatment duration may also be shorter with targeted phototherapy, unless very large areas are treated, and visits for treatment can be less frequent [31]. Moreover, refractory skin lesions not treated adequately with full-body phototherapy may respond to a more powerful, directed radiation treatment.

●Targeted phototherapy is particularly useful to treat difficult-to-treat anatomical locations. Lesions of the scalp, nose, genitals, oral mucosa, and ears are more easily and conveniently treated with targeted phototherapy [23].

●Targeted phototherapy devices are available for home use. Patient-reported benefits include less time away from work, better compliance, and improved quality of life [13,14].

Disadvantages — Targeted therapy is not generally used for lesions affecting greater than 10 percent of the body surface area. More extensive disease is more easily and conveniently treated with conventional broadband or narrowband ultraviolet B (NBUVB) treatments.

Targeted phototherapy is not widely available and is more expensive than conventional phototherapy, due to the higher cost of the machines for targeted phototherapy compared with the equipment used for full-body ultraviolet B (UVB) treatment.

SAFETY MEASURES — Safety measures and contraindications should be reviewed with the patient prior to initiating treatment with targeted phototherapy. Safety measures can include:

●Protecting the skin surrounding the treated area by using a sunscreen with a sun protection factor (SPF) of 50+ or a physical barrier

●Using topical emollients and moisturizers for treated erythematous, dry, or blistering areas

●Avoiding additional sun exposure to treated areas

SHORT- AND LONG-TERM ADVERSE EFFECTS — Short-term adverse effects of targeted phototherapy include localized erythema, burning, skin dryness and flaking, pruritus, and blistering, usually with higher doses. Hyperpigmentation of the treated areas may occur [32].

Long-term adverse effects of targeted phototherapy have not been extensively studied. They are theoretical and may include localized photoaging and possibly photocarcinogenesis. However, the risk of long-term adverse effects is expected to be smaller than with nontargeted phototherapy because a much smaller skin area is exposed to ultraviolet (UV) light when using a targeted approach.

CONTRAINDICATIONS — Absolute contraindications for targeted phototherapy are:

●Xeroderma pigmentosum

●Lupus erythematosus

●Photosensitivity disorders

●Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Relative contraindications to targeted ultraviolet B (UVB) therapy include:

●History of melanoma

●History of nonmelanoma skin cancer

●History of treatment with arsenic or ionizing radiation because of the increased risk for skin cancer

●Immunosuppression (eg, in organ transplant patients)

SUMMARY AND RECOMMENDATIONS

●Principles and mechanisms – Targeted phototherapy is the localized delivery of ultraviolet (UV) light to affected skin with either laser or nonlaser devices that emit a spot of UV light, typically a few square centimeters, in one area. The 308 nm xenon-chloride laser is most commonly used to treat skin conditions. (See 'Principles and mechanisms' above and 'Devices for targeted phototherapy' above.)

●Indications – Indications of targeted phototherapy include inflammatory and lymphoproliferative skin conditions (table 1) involving a limited area of the body or difficult-to-treat areas. (See 'Clinical indications' above.)

●Dosing and regimens – There are no widely accepted protocols for targeted phototherapy. Initial treatment can be based on minimal erythema dose (MED) testing. Subsequent treatments are based upon clinical response and side effects, for a total of 10 treatments or until lesions clear. (See 'Dosing and treatment regimens' above.)

●Advantages of targeted phototherapy – Advantages of targeted phototherapy include less toxicity, fewer treatments, and a lower cumulative UV dose, compared with whole-body phototherapy. Since targeted phototherapy is only delivered to diseased skin, higher doses can be used, resulting in more rapid clearing with fewer treatment sessions. Targeted phototherapy devices are available for home use. Patient-reported benefits include less time away from work, better compliance, and improved quality of life. (See 'Targeted versus full-body phototherapy' above.)

●Safety measures – During targeted phototherapy, the skin surrounding the treated area can be protected by using a sunscreen with a sun protection factor (SPF) of 50+ or a physical barrier. Patients should avoid additional sun exposure to treated areas. (See 'Safety measures' above.)

●Adverse effects – Short-term adverse effects of targeted phototherapy include localized erythema, burning, pruritus, and blistering. Long-term adverse effects have not been extensively studied. They may include localized photoaging and photocarcinogenesis. (See 'Short- and long-term adverse effects' above.)