Newer Aspects in Phototherapy

The concept of phototherapy has undergone a lot of changes in the past 30 years. It started with the emergence of psoralen ultraviolet A (PUVA) for the treatment of psoriasis. The subsequent evolution of Narrow band UVB therapy, Targeted phototherapy, UVA1 therapy, Home phototherapy and the use of LED lamps have revolutionized the treatment of various skin diseases. This article briefly summarizes the advances made in the last few years in the field of phototherapy.


Introduction
Phototherapy (UV-A and UV-B) has become one of the most commonly used modali es of treatment of a variety of skin diseases, although the mechanism of ac on have not been fully understood.Inhibi on of DNA synthesis by UV radia on is proposed as a mechanism in prolifera ng skin diseases.
Phototherapy exerts its therapeu c eff ect, via a number of mechanisms.The major molecular target for ultraviolet B (UVB) radia on is nuclear DNA which absorbs light, genera ng pyrimidine dimers and other photoproducts.This ac on ul mately inhibits DNA synthesis.
Psoralen ultraviolet A (PUVA) is the combined use of psoralen and long-wave UV radia on (UVA).One molecule of psoralen intercalates into the DNA double strand; upon irradia on with UVA, one photon of light is absorbed, followed by binding of a thymine base.The DNA-psoralen crosslink inhibits DNA replica on and causes cell cycle arrest.
Narrow band UVB therapy using 311 nm is increasingly being used in a variety of skin disorders such as psoriasis and vi ligo.
Both UVA and UVB aff ect cytokine produc on of infl ammatory cells, reducing the secre on of infl ammatory cytokines, and also cause apoptosis of lymphocytes. 6

Newer aspects
A lot of advances have been made in phototherapy since its emergence.The indica ons for phototherapy have expanded, newer machines and lamps have emerged and therapeu c protocols have been modifi ed.This ar cle will discuss briefl y regarding the newer advances made in the fi eld of phototherapy.

Targeted phototherapy
Targeted ultraviolet (UV) B phototherapy devices provide a prac cal means to treat localized lesions while sparing harmful eff ects to unaff ected skin. 7The most common and extensively implemented mode of delivery is the 308-nm excimer laser.Although laser treatment is the dominant standard of 308-nm excimer delivery, numerous studies have reported the use of a 308-nm monochroma c excimer nonlaser (MEL) light source.UV light is also used as a source for targeted phototherapy.

Excimer laser
Excimer stands for excited dimer, a diatomic molecule usually of an inert gas atom and a halide atom, which are bound in excited states only.These diatomic molecules have extremely short life me and dissociate releasing the excita on energy through UV photons.These devices are xenon-chloride gas excimer lasers that deliver coherent, monochroma c UVB light of 308-nm wavelength in short impulses and allow for changes in important phototherapeu c parameters such as impulse frequency and light intensity.In addi on to the treatment of psoriasis, excimer lasers can be used for trea ng vi ligo, atopic derma s, and leukoderma. 8veral advantages have been claimed for targeted phototherapy: 9 a.Exposure of involved areas only and sparing of uninvolved areas, thus minimizing acute side eff ects such as erythema and long-term risk of skin cancer over unaff ected skin.b.Quick delivery of energy and thereby shortened dura on of treatment.c.Delivery of higher doses (super-erythemogenic doses) of energy because uninvolved areas are not exposed, higher doses of energy can be delivered selec vely to the lesions, thereby enhancing effi cacy and achieving faster response.d.The maneuverable hand piece allows treatment of diffi cult areas such as scalp, nose, genitals, oral mucosa, ear, etc. e. Easy administra on for children as delivery is hand-held.f.Targeted phototherapy machines occupy less space.
However, targeted phototherapy devices have certain disadvantages; they are more expensive.Also, they are not adequate to treat extensive areas in view of the cost of treatment and me involved in treatment.They are not recommended for use if lesions occur over more than 10% of the body area.High cost and diffi cul es in maintenance are the other disadvantages with this machine.

Fractional targeted phototherapy
Targeted phototherapy delivers a high amount of UV rays over a small area and is used for the treatment of smaller lesions and for lesions resistant to whole body phototherapy using UV chamber.Frac onaliza on of the UV light with the same irradiance to target smaller areas has the addi onal advantage of using fewer shots and also covering larger areas.Since the light is not collimated, it is reasonable to assume that the rays diverge following entry into skin and thus can target larger areas. 10Targe ng very small areas may also minimize the chance of UV burn.

Turban PUVASOL
In the turban PUVASOL therapy, 1 ml of 8-methoxypsoralen (8-MOP) 1% is diluted in 2 liters of water.A clean absorbent co on cloth is soaked into the solu on for 30 seconds and wrapped around the scalp in a turban-like fashion for 5 minutes.The process was repeated four mes.The pa ents were further exposed to sunlight for 5 minutes and the me was gradually increased up to 15 minutes.The treatment was carried out thrice a week.The me of exposure was between 10:00 and 10:15 AM when the ultraviolet UVA : UVB ra o is maximum.The pa ent was advised to avoid sun exposure for few hours a er treatment.A few reports indicate that the treatment is useful in the treatment of alopecia totalis. 11

UVA1
Most recently, ultraviolet A1 (UVA1) phototherapy has emerged as a specifi c UVR phototherapeu c mechanism.High intensity long-wavelength ultraviolet A (340-400 nm; UVA1) lamps were ini ally developed as skin research tools; over me they have proven to be useful for trea ng a number of chronic dermatoses. 12UVA1 units and dosimetry are strikingly diff erent from conven onal UV phototherapy.The therapeu c eff ect of UVA1 is related to the fact that its long wavelength penetrates the dermis more deeply than UVB.UVA1 radia on induces collagenase (matrix metalloproteinase-1) expression, T-cell apoptosis, and depletes langerhans and mast cells in the dermis.UVA1 exposure s mulates endothelial cells to undergo neovasculariza on.Ultraviolet A1 exerts signifi cant therapeu c eff ects in atopic derma s and morphea; there is also evidence for its use in other skin diseases, including cutaneous T-cell lymphoma and mastocytosis.UVA1 therapy also has been shown to be rela vely free of side eff ects associated with other phototherapy regimens, including erythema and cellular transforma on. 13These proper es make UVA1 phototherapy an important treatment op on for many debilita ng skin condi ons.

Home phototherapy
Home phototherapy equipment became commercially available in the early 1980s.Since its introduc on, the use of home phototherapy has expanded and is popular with many psoriasis pa ents.Units of varying sizes have been designed in trea ng diff erent types of diseases in various anatomic loca ons and distribu on.Smaller, specialized targeted units are useful to treat specifi c body areas and eliminate exposure of unaff ected skin to ultraviolet light.The ability to perform such localized treatment may be more effi cacious in trea ng hand and foot diseases that require more intense regional treatment to penetrate the thick stratum corneum.For pa ents with more diff use or total-body disease, refl ec ng side panels and wings are used to increase the dispersion of ultraviolet rays, thus allowing a greater area to be well-treated in a uniform manner and in a lesser amount of me.
Prior to the ini a on of a home phototherapy regimen, pa ents should undergo examina on their dermatologist to determine skin type and to establish diagnosis.Addi onally, a previous therapeu c response to outpa ent phototherapy should be documented.
The pa ent should be thoroughly educated as to prac cal use issues and goals of phototherapy as well as the an cipated response to and possible sideeff ects of treatment A variety of protocols for home phototherapy have been developed and are tailored to fi t diff erent diseases, skin types, and minimal erythema dose (MED). 14A standard protocol for NB-UVB in the treatment of psoriasis consists of three sessions per week (treatment sessions every other day is most eff ec ve) for a dura on of three months, with ini al treatment me determined by skin type or MED and dose escala on depending on the pa ent's response to treatment and the physician/clinic preferences.For MED-based NB-UVB regimens, 0.7 MED is the most frequently used ini al dose, with recommended range of 0.5 -1.0 MED. 15,16In terms of increase in treatment me, the magnitude of dose increase depends on the pa ent and the provider.There are a variety of strategies to increase treatment me: some increase the dose in increments of 10-20 percent with each treatment session; others use larger dose increments (15-20%) early in the course of treatment followed by smaller increments (10%) later on.Whereas MEDbased therapy is thought to be safest, treatment me based on the pa ent's skin type is more convenient and as such is u lized by many prac oners. 17verse eff ects associated with phototherapy include both acute adverse eff ects such as erythema and burning sensa on and cumula ve, dose-related eff ects that occur with prolonged use.However, the exis ng data demonstrates no diff erences in acute adverse events or total cumula ve ultraviolet dose and there are no data sugges ng that home phototherapy is less safe than standard outpa ent treatment. 18

Newer lamps
One of the major technological breakthroughs in the last decade is represented by the diversifi ed medical applica ons of light-emi ng diodes (LEDs).LEDs emi ng in the ultraviolet (UV) B spectrum might serve as a more convenient alterna ve for targeted delivery of phototherapy in infl ammatory skin diseases such as psoriasis.Kemény et al. 19 reported the use of UVB LEDs in the treatment of psoriasis.The device used in their study emits 1 mW cm −2 at a central wavelength of 310 nm with 15-nm bandwidth, near to the op mum wavelength for the treatment of psoriasis.They show that this device can treat small areas of psoriasis, as would be expected from such an output.UVA LED 20 sources are also now available with outputs in excess of 4000 mW cm −2

Conclusion
As new data emerge, the role of phototherapy in trea ng many newer diseases is emerging.The scope for phototherapy is broadening with a lot of research into various aspects and it may emerge as one of the most promising dermatotherapies in the future.