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Dermatologia 2021;96(4):397---407 Anais Brasileiros de Dermatologia 2021;96(4):397---407 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br CONTINUING MEDICAL EDUCATION Phototherapyଝ,ଝଝ ∗ Norami de Moura Barros , Lissiê Lunardi Sbroglio , Maria de Oliveira Buffara , Jessica Lana Conceic¸ão e Silva Baka , Allen de Souza Pessoa , Luna Azulay-Abulafia Department of Dermatology, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Received 3 December 2019; accepted 2 March 2021 Available online 2 April 2021 Abstract Of all the therapeutic options available in Dermatology, few of them have the his- KEYWORDS tory, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are Phototherapy; currently the most common types of phototherapy used. Although psoriasis is the most frequent PUVA therapy; indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous Ultraviolet therapy sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible. © 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Introduction Phototherapy consists of the therapeutic use of ultraviolet (UV) radiation. It can be performed with exposure to sun- ଝ light, ultraviolet A (UVA) or ultraviolet B (UVB) radiation. How to cite this article: Barros NM, Sbroglio LL, Buffara MO, Baka The wavelengths administered and the UV radiation doses JLCS, Pessoa AS, Azulay-Abulafia L. Phototherapy. An Bras Dermatol. 1 2021;96:397---407. vary according to the proposed indication. ଝଝ Study conducted at the Department of Dermatology, Hospi- Ultraviolet radiation (UVR) encompasses wavelengths tal Universitário Pedro Ernesto, Universidade do Estado do Rio de ranging from 200 to 400 nm. Janeiro, Rio de Janeiro, RJ, Brazil. It is divided into: ∗ Corresponding author. E-mail: [email protected] (N.M. Barros). https://doi.org/10.1016/j.abd.2021.03.001 0365-0596/© 2021 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). N.M. Barros, L.L. Sbroglio, M.O. Buffara et al. UVA (320---400 nm), which is subdivided into UVA2 Phototherapy started being used in Brazil in the 1980s. (320---340 nm) and UVA1 (340---400 nm). It was also in this decade that a new type of photother- UVB, subdivided into broadband UVB (290---320 nm) and apy was introduced, extracorporeal photochemotherapy, 2 narrowband UVB (NB-UVB), from 311 to 313 nm. initially for the treatment of cutaneous erythrodermic T-cell 8 UVC (200---290 nm), which is blocked by the ozone layer lymphoma. and by the oxygen of the atmosphere and which is not used A major advance in the field of phototherapy was the 1 for phototherapy. development of UVA1 lamps (340---400 nm), which occurred The benefits of phototherapy have been recognized since in the early 1990s. Used mainly for the treatment of atopic th the 20 century BCE. Although psoriasis is the most frequent dermatitis and scleroderma, this modality of treatment does indication, phototherapy has been used successfully in sev- not require the use of psoralen, thanks to its greater pene- 9 eral other dermatoses, such as atopic dermatitis, vitiligo, trating power. cutaneous T-cell lymphoma, and cutaneous sclerosis, among More recently, in 1997, phototherapy with an excimer others. Using controlled and repeated UV exposures, it is laser (UVB - 308 nm), a subtype of NB-UVB, was introduced possible to induce regression or control the evolution of for the treatment of psoriasis and is currently used in other 3 2,6 these dermatoses. diseases, such as vitiligo. Most of the time, phototherapy is used in combination From the heliotherapy practiced in Ancient Egypt to the with topical or systemic medications for better disease development of the excimer laser, phototherapy has been 4 control. part of the therapeutic arsenal of Dermatology, establishing Just like any other therapy, it has side effects. Most of its importance in clinical practice. the time, they are acute and transient, including erythema and burns, and attention should be paid to possible adverse 4 Mechanism of action events during treatment. Accessibility to the phototherapy unit is an important lim- UVR is absorbed by the chromophores (molecules that have iting factor for undergoing this type of treatment, despite 5 the capacity to absorb certain wavelengths), such as DNA, the degree of satisfaction reported by users. nucleotides, lipids, amino acids, trans-urocanic acid, and melanin. UVR causes changes in the structure and function of History chromophores. The molecules thus modified are called pho- toproducts, which participate in apoptosis, inflammation, 1 immunosuppression, and photocarcinogenesis. For many centuries, sunlight treatment or heliotherapy has The depth reached in the skin by each radiation type been instituted for the treatment of skin diseases. In Egypt depends directly on its wavelength. UVB radiation (broad- and India, 3,500 years ago, people had the habit of using band and NB-UVB) has a shorter length, being absorbed by plant extracts or seeds, with subsequent exposure to the 6 the epidermis and the superficial portion of the dermis. The sun for the treatment of skin diseases. th UVA waves (1 and 2) have a longer length, penetrating up to In the 19 century, the modern era of the use of light 1 the dermis. started. Downes and Blunt, in 1877, published results of Both UVA (PUVA or UVA1) and UVB (broadband and research in which exposure to light inhibited fungal and 7 NB-UVB) have immunosuppressive and antiproliferative bacterial growth. 1 th effects. In the 20 century, phototherapy was recognized as a The reduction in the number of macrophages, the inhi- medical science after Niels Finsen received the Nobel Prize bition of inflammatory cytokine production (IL-2, IL-8, IL-9, of Medicine in 1903. Twenty years later, William Henry IL-17, IL-22, IL-23, TNF-␣, and IFN-␥) and IL-10 (immuno- Goeckerman started using a lamp that emitted mainly UVB, suppressive cytokine) induction can occur in both the UVR together with coal tar to treat psoriasis. This treatment 6,7 spectra and contribute to the anti-inflammatory effect of became very popular and was used for decades. phototherapy.1 The increase in the effectiveness of phototherapy started Although there are still gaps in the knowledge about the in 1947, with the isolation of 8-Methoxypsoralen (8-MOP) and UVR mechanisms of action, one can didactically separate the 5-Methoxypsoralen (5-MOP), derived from the Ammi Majus 7 most characteristic effects of UVB (broadband and NB-UVB) Linn flower. and UVA, subdivided in this topic into PUVA and UVA1: There are reports on the use of this plant that dates th back to the 13 century, when the Arab physician Ibnal-Bitar mentioned in his book ‘‘Mofradat El-Adwiya’’ the effects of UVB (broadband, NB-UVB and excimer laser) ingesting Ammi Majus extracts, followed by exposure to sun- light, for vitiligo repigmentation. This treatment was the - Induces the apoptosis of keratinocytes and T-cells through oldest form of what is currently called photochemotherapy, direct molecular alteration of DNA and, therefore, causes a modality defined as the ingestion of a psoralen followed the inhibition of its transcription and interrupts the cell by exposure to UVA (320---400 nm). In 1974, the term PUVA cycle. (Psoralen-ultraviolet A) was created by Thomas B. Fitz- - Promotes the conversion of trans-urocanic acid (trans- 7 patrick and John Parrish to name this therapeutic modality. UCA) into cis-urocanic acid (cis-UCA), which leads to The development of photochemotherapy with PUVA inhibition of contact hypersensitivity, in addition to paved the way for the research into new modalities. NB-UVB impairing the function and reducing the amount of radiation (311---313 nm) was discovered in 1988, gradually antigen-presenting cells. 6 replacing broadband UVB (290---320 nm). - Reduces the number of natural killer cells. 398 Anais Brasileiros de Dermatologia 2021;96(4):397---407 - Intensifies the production of reactive oxygen species, UVA1 (340---400 nm) reaches the epidermis, the middle 3 leading to increased synthesis and enzyme activity of the and deep dermal components, especially blood vessels. cellular antioxidant system, which modifies the immune UVA2 (320---340 nm) resembles UVB, with more superficial 1,3 3 reaction pattern. penetration. UVA (PUVA and UVA1) PUVA The UVA wavelength is not so easily absorbed by the DNA Before the development of UVA1 lamps, the UVA photother- molecule. It acts mainly through other chromophores, gen- apy that was in use was PUVA, a method that by definition erating free radicals (reactive oxygen species), which cause requires the use of psoralens. Psoralen is a photosensitizing indirect damage to the genetic material, promoting DNA substance that can be used systemically via the oral route 9 degradation. (capsule) or topically. The latter route employs psoralen in cold cream, alcoholic solution, emulsion, or diluted (in a full 4 PUVA or partial bath). For patients with gastric intolerance, there is the possibility of the systemic use of psoralen through 11 rectal administration (suppository). - Always performed after the administration of psoralens, Treatment with systemic PUVA (oral or rectal administra- furocoumarin compounds that act as chromophores for tion) involves the use of methoxypsoralen two hours before UVA.
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