INTRODUCTION — Broadband ultraviolet B (UVB) radiation (280 to 320 nm), with or without topical tar, has been used for the treatment of moderate to severe psoriasis for decades. In the early 1980s, the observation that wavelengths around 311 nm were more effective than broad-spectrum UVB in clearing psoriasis led to a major advancement in phototherapy with the development of fluorescent lamps emitting selective UVB spectra in the range of 311 to 313 nm (narrowband UVB) [1,2].
Narrowband UVB has since become the type of phototherapy most frequently used for the treatment of psoriasis and a wide range of skin diseases, including atopic dermatitis, vitiligo, early stages of mycosis fungoides, and pruritic disorders (table 1) [3-5]. Narrowband UVB is a low-cost treatment and may delay or avoid costly third-line treatments for many patients with inflammatory dermatoses [6].
This topic will discuss the mechanism of action, treatment protocols, indications, and adverse effects of UVB phototherapy. Psoralen plus ultraviolet A (PUVA) photochemotherapy, ultraviolet A1 (UVA1) phototherapy, and targeted phototherapy are discussed separately. The use of UVB for the treatment of specific skin conditions are discussed in the dedicated topics.
●(See "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)
●(See "UVA1 phototherapy".)
●(See "Targeted phototherapy".)
PRINCIPLES AND MECHANISMS — UVB radiation (280 to 320 nm) is absorbed in the epidermis and superficial dermis by molecules called chromophores, which include deoxyribonucleic acid (DNA), urocanic acid (a breakdown product of histidine abundantly present in stratum corneum), keratin, and melanin. Although nuclear DNA is the main chromophore in the skin, there is evidence that UVB also targets cytoplasm and cell membrane components, including cell surface receptors, kinases, phosphatases, and transcription factors [7].
Photochemical reactions convert the chromophores into photoproducts that stimulate signal transduction pathways leading to the activation of transcription factors, cytokine secretion, and a variety of cellular responses, including cell cycle arrest and apoptosis [8].
Decreased cell proliferation, immunosuppression, and T cell apoptosis may contribute to the UVB-mediated suppression of disease activity in inflammatory and lymphoproliferative skin disorders [9,10]. How phototherapy exerts its effects in various diseases amenable to this treatment is not entirely known. The most information is available for psoriasis. It improves impaired resting regulatory T cells and increases activated regulatory T cells in patients with psoriasis [11]. In psoriasis, the suppression of the interleukin (IL) 23/IL-17 axis also appears to be important [12].
Effects on DNA — The most important chromophore in the skin is nuclear DNA. The absorption of UVB by nucleotides leads to the formation of cyclobutane pyrimidine dimers and pyrimidine (6-4)-photoproducts, which play a key role in both UVB therapeutic effect and toxicity. The tumor suppressor gene p53 has a central role in the regulation of the cellular responses to DNA damage, which include cell cycle arrest, DNA repair, and apoptosis [13].
The majority of UV-induced DNA lesions are not translated into a mutation, because cells have a variety of antimutagenic mechanisms that prevent mutation formation at sites of DNA damage. DNA lesions that are not repaired may lead to cytosine-thymine transition mutations, which represent the initial event in skin carcinogenesis, or to cell death.
Severely damaged cells ("sunburn cells") undergo apoptosis as the result of a "cellular proofreading" mechanism in which p53 erases aberrant cells through the activation of the death receptor Fas and proapoptotic effector proteins Bax (Bcl-2–associated X protein), Bak, Bid, and PUMA [14]. Apoptosis of UVB-damaged cells occurs not only in keratinocytes but also in T cells infiltrating the dermis or epidermis. T cells apoptosis is the main mechanism underlying the depletion of the neoplastic infiltrate in mycosis fungoides.
Effects on protein-coding genes — Narrowband UVB treatment induces expression of the protein-coding genes WNT7B, WNT10B, and TCF7L2 in psoriatic skin, suggesting a potential role of these genes in psoriasis pathogenesis [15].
Effects on the immune system — UVB radiation induces the release of a variety of proinflammatory and immunosuppressive cytokines from keratinocytes and T cells. Proinflammatory cytokines (eg, IL-1, IL-6, IL-8, and TNF-alpha) play an important role in local and systemic sunburn reaction [7]. (See "Sunburn", section on 'Pathogenesis'.)
The mechanisms involved in UVB-induced immunosuppression are complex and only partially understood. They involve:
●Downregulation of interferon (IFN)-gamma, IL-2, and IL-12 and increased secretion of IL-4 and IL-10 [7,10,16,17]
●Functional impairment of epidermal Langerhans cells and dermal dendritic cells and reduced expression of ICAM-1 and other adhesion molecules, resulting in a reduced capacity of antigen presentation to effector T cells [18]
●Reduced activation of effector and memory T cells [19]
●Induction of T cells with regulatory/suppressive activity [8]
●Apoptosis of dermal T cells
●A reduction in myeloid inflammatory dendritic cells and their products (inducible nitric oxide synthase [iNOS], IL-23, and IL-20) associated with a decrease in T cells and additional pathogenic cytokines (IL-17, IFN-gamma, and IL-22) [12]
Despite its immunosuppressive effects, UVB phototherapy is not associated with an increased risk of cutaneous infections, with the exception of reactivation of Herpes simplex infection. Studies suggest that UVB radiation may induce keratinocyte-derived antimicrobial peptides that prevent skin colonization by pathogens [20].
DEVICES FOR BROADBAND AND NARROWBAND UVB — Devices for broadband UVB therapy utilize fluorescent lamps emitting a wide range of wavelengths. Approximately two-thirds of the output is in the UVB range (280 to 320 nm), and the rest is primarily in the ultraviolet A (UVA) range (320 to 400 nm) (figure 1) [21].
Devices for narrowband UVB therapy use the TL-01 fluorescent lamps that emit UVB in the range of 311 to 313 nm [3].
Different phototherapy devices are designed to treat the whole body (picture 1A-B), localized regions (picture 2), or only lesional skin. Those used for large body surface areas resemble booths that patients enter for each treatment. Smaller devices, including small handheld units, are used to treat limited areas (eg, palms, soles, scalp).
CLINICAL INDICATIONS FOR UVB THERAPY — Most common indications for UVB therapy, in particular for narrowband UVB, include moderate to severe psoriasis that is unresponsive to topical therapy, severe atopic dermatitis, and vitiligo [22-25]. Narrowband UVB is also indicated for the prevention of polymorphous light eruption [26]. Additional indications for UVB phototherapy are summarized in the table (table 1).
The use of UVB phototherapy for the treatment of specific skin conditions is discussed separately.
●(See "Management of severe atopic dermatitis (eczema) in children", section on 'Phototherapy'.)
●(See "Polymorphous light eruption", section on 'Photohardening'.)
●(See "Treatment of early stage (IA to IIA) mycosis fungoides", section on 'Phototherapy'.)
●(See "Pityriasis lichenoides chronica", section on 'Phototherapy'.)
●(See "Lymphomatoid papulosis", section on 'Phototherapy'.)
●(See "Parapsoriasis (small plaque and large plaque parapsoriasis)".)
●(See "Pruritus: Therapies for generalized pruritus", section on 'Phototherapy'.)
●(See "Prurigo nodularis", section on 'Phototherapy'.)
Guidelines for the use of narrowband UVB therapy for the treatment of psoriasis and other skin disorders have been published in Europe, the United States, and Australia [5,27-31].
DOSIMETRY AND TREATMENT PROTOCOLS
Determination of the initial dose — Before initiating phototherapy, the initial irradiation dose for the individual patient must be determined. The starting dose can be established by determining the minimal erythema dose (MED) with phototesting or by using an empirical method based upon the patient’s skin phototype (table 2).
The patient’s MED is determined by exposing six small template areas (eg, circles of 1 cm diameter) of nonexposed skin (lower back, buttocks) to an incremental series of UVB irradiations. Increases are made by fixed values (eg, 10 mJ/cm2) or by a fraction (eg, 40 percent) of the previous dose. The MED is defined as the lowest dose that causes a minimally perceptible erythema reaction 24 hours after irradiation. Sunbathing or exposure to solaria must be avoided before phototesting.
Treatment is generally started with an initial dose of UVB equal to 50 to 70 percent of the MED. It is important to document the type of lamp used for MED determination, since values obtained with broadband or narrowband sources are markedly different (table 3). Narrowband UVB is approximately 10 times less erythemogenic than broadband UVB. Thus, MEDs determined by using narrowband UVB devices are considerably higher than those determined with broadband sources.
The determination of the initial dose based upon the patient’s skin phototype may not reflect the actual sensitivity of a particular individual. However, this method is used for practical reasons in many phototherapy centers, particularly in the United States. The initial irradiation doses of broadband and narrowband UVB for the treatment of psoriasis recommended by the American Academy of Dermatology are listed in the table (table 4) [31].
Treatment initiation, frequency, and dose increments — Treatment is generally started with an initial dose equal to 70 percent of the MED for broadband UVB and 50 percent of the MED for narrowband UVB or according to the Fitzpatrick skin type (table 4). Doses are then gradually increased to the maximum tolerated dose or 2000 to 5000 mJ/cm2, whichever is lower [31]. Treatments are given two to five times per week. The duration of each treatment ranges from several seconds (at the beginning of treatment) to several minutes, depending upon the type of irradiation unit used.
Since UVB-induced erythema peaks at 24 hours after exposure, the radiation dose should not be increased on consecutive days for patients receiving more than three treatments per week. The dose increase is determined based upon the effects of the previous treatment (ie, presence and intensity of erythema). Dose increments usually vary between 10 and 40 percent of the last used dose.
The goal of dose increment is to achieve a minimally perceptible erythema, which is the clinical indicator of optimal dosimetry. As an example, in a patient receiving three treatments per week, the UVB dose can be increased by 40 percent if the patient has no evidence of erythema from the previous treatment. In contrast, if a mild erythema is noticeable, the dose increase should be limited to 20 percent of the previous dose. If a mild erythema persists even with smaller dose increments, the dose should be maintained until erythema subsides.
In a patient receiving five treatments per week, smaller dose increments should be given every other session (30 percent in the absence of erythema; 15 percent if mild erythema is noted; no increase if there is persistent erythema).
In patients who develop intense or painful erythema, irradiation is stopped until the symptoms subside and then resumed. Treatment is continued until complete remission is achieved or no further improvement can be obtained with continued phototherapy.
Maintenance therapy — Maintenance therapy may prolong remission. However, the optimal maintenance schedules for specific diseases have not been determined. For the treatment of cutaneous T cell lymphoma, most therapists perform maintenance treatment for several months to a year [32,33]. (See "Treatment of early stage (IA to IIA) mycosis fungoides", section on 'Phototherapy'.)
For the treatment of psoriasis, some centers advocate a two-month maintenance phase with twice-weekly exposures for one month and once-weekly exposures for another month. The last effective UVB dose is given throughout the maintenance phase. If relapses occur during the maintenance phase, treatment frequency and UVB dose are increased until clearing is achieved.
In a small randomized trial, 46 patients with psoriasis who had achieved a 75 percent reduction of the Psoriasis Area and Severity Index (PASI) after 12 weeks of narrowband UVB therapy were assigned to maintenance treatment or observation for two months [34]. More patients in the maintenance group than in the observation group (12 of 22 versus 8 of 24) remained in remission after two months, although the difference was not statistically significant.
Combination therapies — Both topical and systemic agents can be used in conjunction with UVB phototherapy to improve its efficacy, reduce the cumulative UVB dose, and minimize long-term side effects.
●Emollients (eg, petrolatum, salicylic acid ointments) increase the transmission of UV radiation by altering the optical properties of the stratum corneum [35]. Application of a thin layer of emollient such as petrolatum before UVB exposure is used in some institutions. However, the benefits of emollients before UVB exposure have not been evaluated in randomized trials.
●Topical dithranol, vitamin D derivatives, and retinoids in conjunction with narrowband UVB phototherapy have been reported as beneficial for patients with psoriasis or vitiligo in a few small uncontrolled studies [36-40]. Such combinations can possibly also enhance the efficacy of targeted phototherapy. (See "Targeted phototherapy".)
●Systemic retinoids such as acitretin increase the efficacy of phototherapy, particularly in patients with chronic plaque psoriasis [41]. Retinoids hasten and enhance the response to phototherapy and reduce treatment frequency, duration, and cumulative UVB doses [31,42]. However, despite its many advantages, retinoid-UVB therapy is infrequently used.
●Methotrexate may have a synergistic effect with UVB therapy for the treatment of psoriasis. In a small randomized trial, patients treated with methotrexate and narrowband UVB achieved a >90 percent reduction of the baseline Psoriasis Area and Severity Index (PASI) more rapidly than patients treated with placebo plus narrowband UVB (median time 4 weeks versus >24 weeks) [43]. However, further studies are needed to confirm the efficacy of this combination therapy and evaluate potential short- and long-term adverse effects.
●Several reports suggest that narrowband UVB phototherapy may enhance the therapeutic response to biologics [44-49]. However, long-term safety data on these combinations are not available and there is concern that concurrent treatment with anti-TNF agents and narrowband phototherapy may increase the risk of photocarcinogenesis [46,50-53]. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".)
TARGETED PHOTOTHERAPY WITH 308 NM DEVICES — Lasers and lamps emitting monochromatic excimer light at 308 nm wavelength have a clinical use similar to narrowband UVB therapy. Excimer lasers emit a higher amount of radiation over a shorter period of time than conventional narrowband UVB devices and are particularly useful for the treatment resistant psoriasis plaques that are unresponsive to other treatments or located in difficult areas (eg, scalp, palms, soles, knees, and elbows) [54]. A pilot study reports possible useful combinations with topical agents [55]. Excimer lamps may be used to treat large body areas but have a lower power density than lasers. Targeted phototherapy may also be a treatment modality for stable vitiligo, localized chronic dermatoses (eg, psoriasis, localized scleroderma, granuloma annulare, lichen planus, lichen simplex chronicus), lymphomatoid papulosis, and alopecia areata [56-61].
Targeted phototherapy is discussed in detail separately. (See "Targeted phototherapy".)
SAFETY MEASURES — Safety measures for patients undergoing UVB phototherapy include:
●Wearing UV-blocking goggles to protect the eyes and prevent conjunctivitis and photokeratitis
●Protecting the face (if not involved in the disease process) either by using a sunscreen with a sun protection factor (SPF) of 50+ or a cloth barrier
●Protecting the genitalia (if not involved in the disease process) by wearing underwear
●Avoiding concurrent natural sun exposure
SHORT- AND LONG-TERM ADVERSE EFFECTS — Short-term adverse effects of UVB phototherapy include erythema, skin dryness, pruritus, blistering, and reactivation of herpes simplex virus (table 5).
Long-term adverse effects include photoaging and the possibility of photocarcinogenesis. The carcinogenic potential of narrowband phototherapy has not been determined. A systematic review of the carcinogenic risk associated with psoralen plus ultraviolet A (PUVA) photochemotherapy and narrowband UVB therapy for psoriasis suggests that narrowband UVB therapy does not increase the risk of skin cancer [62]. However, there is a need for larger studies with longer follow-up time to assess the risk of skin cancer among patients treated with narrowband UVB phototherapy.
CONTRAINDICATIONS — Absolute contraindications for UVB phototherapy are [5]:
●Xeroderma pigmentosum and other rare photosensitive genodermatoses (eg, trichothiodystrophy, Cockayne syndrome, Bloom syndrome, Rothmund-Thomson syndrome)
●Genetic disorders associated with increased risk of skin cancer (eg, Gorlin syndrome, oculocutaneous albinism)
Relative contraindications to UVB therapy include:
●Lupus erythematosus
●History of photosensitivity diseases (eg, chronic actinic dermatitis, solar urticaria)
●History of melanoma
●History of nonmelanoma skin cancer
●History of treatment with arsenic or ionizing radiation because of the increased risk for skin cancer
●Immunosuppressive therapy in organ transplant recipients
SUMMARY AND RECOMMENDATIONS
●Principles of UVB phototherapy – The main cytochemical target of ultraviolet B (UVB) is nuclear DNA. The UVB-induced DNA damage stimulates signal transduction pathways leading to the activation of transcription factors, cytokine secretion, immunosuppression, and a variety of cellular responses, including cell cycle arrest and apoptosis. (See 'Principles and mechanisms' above.)
●Devices for UVB phototherapy – Devices for broadband UVB therapy utilize fluorescent lamps emitting a wide range of wavelengths, mostly in the UVB range (280 to 320 nm) and, in part, in the ultraviolet A (UVA) range (figure 1). Devices for narrowband UVB therapy use the TL-01 fluorescent lamps that emit UVB in the range of 311 to 313 nm. (See 'Devices for broadband and narrowband UVB' above.)
●Dosimetry
•Initial dose – Treatment is generally started with an initial dose of UVB equal to 50 to 70 percent of the minimal erythema dose (MED) or at a dose determined by the patient’s phototype (table 4). It is important to document the type of lamp used for MED determination, since values obtained with broadband or narrowband sources are markedly different (table 3). (See 'Dosimetry and treatment protocols' above.)
•Dose increments – The radiation dose is then gradually increased by 10 to 40 percent of the previous dose. The goal of dose increment is to achieve a minimally perceptible erythema, which is the clinical indicator of optimal dosimetry. Treatment is continued until complete remission is achieved or no further improvement can be obtained with continued phototherapy. The role for maintenance therapy is uncertain. (See 'Treatment initiation, frequency, and dose increments' above.)
●Indications – The most common indications for UVB therapy, in particular for narrowband UVB, include moderate to severe psoriasis that is unresponsive to topical therapy, severe atopic dermatitis, and vitiligo (table 1). (See 'Clinical indications for UVB therapy' above.)
●Safety measures – During UVB phototherapy, the eyes must be protected with UV-blocking goggles. The face, genital area, and skin that is not involved must be protected with a sun protection factor (SPF) 50+ sunscreen or a cloth barrier. (See 'Safety measures' above.)
●Adverse effects – Short-term adverse effects of UVB phototherapy include erythema, skin dryness, pruritus, blistering, and increased frequency of recurrent herpes simplex (table 5). Long-term adverse effects include photoaging and photocarcinogenesis, although the carcinogenic potential of narrow band UVB is less established. (See 'Short- and long-term adverse effects' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Herbert Hönigsmann, MD (deceased), who contributed to earlier versions of this topic review.
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