Am J Clin Dermatol DOI 10.1007/s40257-016-0176-6

THERAPY IN PRACTICE

Ultraviolet B Phototherapy for Psoriasis: Review of Practical Guidelines Dhwani Mehta1 • Henry W. Lim1

Ó Springer International Publishing Switzerland 2016

Abstract Psoriasis is an inflammatory skin condition that affects approximately 2 % of people worldwide. Topical treatments, systemic treatments, biologic agents, and phototherapy are all treatment options for psoriasis. Ultraviolet (UV) B phototherapy is most appropriate for patients with [10 % affected body surface area who have not responded to topical treatments. This review outlines the use, dosage, safety, and efficacy of narrowband UVB (NB-UVB) and targeted phototherapy. NB-UVB and excimer laser are effective treatment options for psoriasis; they are administered two to three times weekly until clearance followed by maintenance treatment before discontinuation. Longterm data on NB-UVB indicate that it has a good safety profile. NB-UVB is commonly used with adjunctive topical treatments such as emollients, calcipotriene, corticosteroids, retinoids, and tar. NB-UVB can be used in selected patients with traditional systemic agents such as methotrexate, mycophenolate mofetil, and cyclosporine, although the duration of the combined treatment should be kept to a minimum and patients need to be closely monitored. Acitretin can be safely used with phototherapy, but robust data on the combination use of biologic agents or phosphodiesterase inhibitors with phototherapy are lacking.

& Henry W. Lim [email protected] Dhwani Mehta [email protected] 1

Department of Dermatology, Henry Ford Hospital, Henry Ford Medical Center-New Center One, 3031 West Grand Blvd, Suite 800, Detroit, MI 48202, USA

Key Points Psoriasis is an inflammatory condition with cytokines such as tumor necrosis factor-a, interferon-c, and interleukin (IL)-17 being implicated in the disease. Narrowband ultraviolet B is a safe and effective treatment option for psoriasis; it can be combined with other topical and systemic treatment regimens, including biologic agents. Limited evidence is present at this time for the use of phosphodiesterase inhibitors and IL-17 inhibitors in combination with phototherapy.

1 Introduction Psoriasis is an inflammatory skin condition that affects people worldwide. The prevalence of psoriasis varies geographically; it is approximately 2 % in the USA [1]. Psoriasis can present at any age, with peaks at ages 15–20 and 55–60 years. Genetic, environmental, geographic, and infectious risk factors have all been linked with psoriasis [1, 2]. Psoriasis is a disorder that is related to a genetic-based dysregulation in the immune system. Eight chromosomal loci, PSOR I–VIII, have been identified as being linked to psoriasis. PSOR I (or HLA-Cw6) is a major susceptibility gene for psoriasis and is linked to early-onset psoriasis. Psoriasis is also considered to be an immune-mediated disease since psoriatic plaques show an increased number of T cells, Langerhans cells, and neutrophils [2]. Cytokines

D. Mehta, H. W. Lim

such as tumor necrosis factor (TNF)-a, interferon (IFN)-c, interleukin (IL)-12, and IL-23 show increased expression in psoriatic plaques. Specifically, IL-23 induces production of IL-17A, IL-17F, and IL-22 by activating T helper (Th)17 cells [3]. The worsening of psoriasis with IFN-c and improvement of psoriasis with the use of immunosuppressants and biologics such as TNF-a inhibitors and IL12/-23 and IL-17 inhibitors support the theory of immune dysregulation [2–4]. Psoriasis presents as well-circumscribed, erythematous papules and plaques with overlying silver scale. Psoriatic plaques can be asymptomatic, pruritic or painful [1, 2]. Psoriasis can affect various parts of the body such as the scalp, elbows, knees, lumbosacral areas, palms and soles, and body folds. It can present as various types such as plaque, guttate, flexural, erythroderma, and pustular [1]. Treatment options for psoriasis include topical treatments, oral treatments, phototherapy, and biologics. Because the quality of life of patients with psoriasis has been noted to be equivalent to or worse than that of patients with other chronic conditions such as diabetes mellitus, optimizing treatment for psoriatic patients is essential [2]. This review focuses on the practical aspects of the use of phototherapy, specifically ultraviolet (UV) B phototherapy for psoriasis. Consensus and systematic review articles were searched using keywords such as ‘‘psoriasis,’’ ‘‘phototherapy,’’ ‘‘narrowband UVB,’’ ‘‘topical treatment,’’ ‘‘biologics,’’ and ‘‘systemic treatment’’.

2 Overview of Phototherapy Phototherapy is the use of UV with or without the use of photosensitizers; it is an efficacious and cost effective form of treatment that has been a mainstay therapy for psoriasis since Dr. Alderson described the use of heliotherapy in psoriasis in 1923, which was further expanded when Dr. Goeckerman used coal tar and UV radiation from hot quartz mercury lamps in 1925 [5, 6]. Subsequently, broadband (BB)-UVB (280–320 nm) was used as the light source, followed by narrowband (NB)-UVB (311–313 nm) in the 1980s. NB-UVB is currently the most widely used form of phototherapy for psoriasis worldwide [7]. The use of 8-methoxypsoralen and UVA (PUVA) was introduced in 1974 as a form of photochemotherapy. Psoralen intercalates with DNA base pairs; in the presence of UVA, it results in cross-linking of the double strands of DNA, which induces apoptosis. While PUVA is a form of photochemotherapy, for simplicity, the term phototherapy will be used to cover PUVA in this article [7, 8, 10]. Finally, targeted phototherapy was introduced in 1997 [7, 10], and is now also widely used for the treatment of psoriasis.

A therapeutic mechanism of phototherapy in psoriasis is through immunomodulation. UV directly affects Langerhans cells in the epidermis and inhibits their ability to present the antigen to the T cell. By doing so, it indirectly affects cytokines and adhesion molecules that are overexpressed in psoriatic plaques. Phototherapy also downregulates cytokine expression, and changes cytokine profiles from a Th2 to a Th1 response [9, 10]. Th17 cells are also thought to be downregulated. Another proposed mechanism is that phototherapy inhibits epidermal hyperproliferation and angiogenesis by interfering with the synthesis of proteins and nucleic acids [9, 10]. 2.1 Ultraviolet (UV) B Phototherapy Modalities Among all forms of phototherapy for psoriasis, BB-UVB has the longest history. Its widespread use began shortly after the description of what is now known as Goeckerman therapy in 1925. Since the introduction of NB-UVB in the mid-1980s, BB-UVB has gradually been replaced by NBUVB [11]. NB-UVB delivers radiation with a narrow emission peak at 311 ± 2 nm; it has been shown to have a better efficacy than BB-UVB, and has clearance and remission rates equivalent to PUVA [10–12]. According to the 2009 Cochrane review, NB-UVB is the preferred treatment rather than PUVA because of its convenience of administration with less potential for the long-term adverse effect of carcinogenesis; however, PUVA is considered to be an appropriate option for patients with high Psoriasis Area Severity Index (PASI) scores who are not well-controlled with NB-UVB [9, 24]. The American Academy of Dermatology (AAD) and European S-3 Guidelines currently recommend NB-UVB as the first-line phototherapy for psoriasis [10, 11]. NBUVB can also be used successfully in combination with other treatment modalities [7, 8, 10], and home NB-UVB therapy is an option for compliant and motivated patients as well as for maintenance therapy [10]. Targeted UVB phototherapy is used to treat localized psoriatic plaques. The excimer (308 nm) laser or light has been shown to have good efficacy in treating localized or resistant psoriasis lesions. It is also useful to treat scalp psoriasis; by parting the hair, it can effectively deliver UVB to the hair-bearing areas. Studies have shown that 61 % of patients had 75 % reduction in their severity score. Also, remission time after targeted phototherapy is equivalent to or even better than standard topical therapies such as topical corticosteroids, calcipotriene, and retinoids [16–18]. All forms of phototherapy have to be performed by appropriately trained individuals, with the supervising dermatologist readily available for consultation and, if

UVB Phototherapy for Psoriasis

needed, evaluation of patients [10]. Most NB-UVB booths now have an internal metering device, a radiometer, which calculates the time needed to deliver a given dose. It is also important to keep in mind that internal broad band radiometers need to be regularly calibrated according to the findings of the spectroradiometer (see below). At our center (Henry Ford Hospital, Detroit, MI, USA), measurement is performed with an external spectrophotometer every 3 months. Lamps need to be replaced once the bulb has been used for 200–350 h or when they have become dark at either end. It should be noted that all the lamps in a given booth must be replaced at the same time to avoid the unevenness of radiation that the patient would otherwise receive. 2.2 Narrowband (NB)-UVB Patient Selection NB-UVB can be used for moderate to severe generalized psoriasis, including guttate psoriasis that does not respond to topical treatment alone. It can also safely be used in women who are pregnant or breastfeeding. In addition, NBUVB can be used in patients with renal and hepatic failure or those who are HIV positive [10]. While phototherapy has a theoretical risk of worsening HIV, this has not been observed clinically with the use of UVB phototherapy [14, 15]. Although safe in children, it is important that the children being treated are able to follow instructions such as standing still in the phototherapy booth, wearing the goggles and keeping them on, and not touching the lamps. For pustular and guttate psoriasis, it is more appropriate to combine NB-UVB with other topical and systemic treatment modalities [10]. For initiation of NB-UVB phototherapy, a minimum body surface area (BSA) with 10 % involvement is usually a requirement. If there is severe focal psoriasis of the scalp, palms, and soles or topical therapy-resistant psoriasis with \10 % BSA, targeted phototherapy can be considered [10, 16, 17]. Targeted UVB phototherapy works well in treatmentresistant areas such as the elbows, knees, and lower legs, and in koebnerized lesions [17]. Targeted phototherapy is discussed in more detail in Sect. 3. 2.3 UVB Phototherapy: Caution and Contraindications UVB phototherapy is contraindicated in patients with lupus erythematosus, xeroderma pigmentosum, or photodermatoses in which the action spectrum is in the UVB range (such as chronic actinic dermatitis and some patients with solar urticaria). Due to the possibility of enhancing photocarcinogenesis, it should be used with caution in patients with a history of arsenic intake,

Table 1 Ultraviolet treatment: contraindications and indications for use with caution Contraindications

Use with caution

Lupus erythematosus

History of melanoma

Xeroderma pigmentosum

History of dysplastic nevi

Photodermatoses in UVB spectrum (i.e., chronic actinic dermatitis, solar urticaria)

History of multiple nonmelanoma skin cancer History of arsenic intake, exposure to ionizing radiation, exposure to PUVA Transplant patients taking immunosuppressive medication

PUVA psoralen ? ultraviolet A, UVB ultraviolet B

ionizing radiation, or extensive previous exposure to PUVA [10, 25]. Phototherapy should also be used with caution in patients with a history of melanoma, atypical nevi, or multiple non-melanoma skin cancers or transplant patients taking immunosuppressive medications (Table 1) [10]. It should be noted that because the action spectrum of almost all photosensitizing medications is in the UVA range, and the emission spectrum of NB-UVB lamps contains a negligible amount of UVA, NB-UVB can be safely administered in patients receiving photosensitizing medications. All patients being considered for phototherapy should have a thorough history taken and a full body skin check before starting therapy. After therapy is initiated, patients require regular follow-up at least every 2–3 months to evaluate their response to therapy, and to make any adjustments needed to the treatment protocol [10]. 2.4 Dosing and Scheduling of NB-UVB Before starting phototherapy, all patients should be provided with basic education on the use of goggles and a genital shield should be provided to all male patients [10]. The guidelines below are recommendations based on the AAD guidelines and experience at our center. Dosing for NB-UVB is based on the Fitzpatrick skin phototype or, alternately, the minimal erythema dose to NB-UVB (MED-B), which is the dose of NB-UVB radiation administered to unprotected skin that produces minimally perceptible erythema covering the entire exposed area at 24 h after irradiation [13]. The starting the dose can vary from 150 to 400 mJ/cm2 based on skin phototype, or 70 % of the MED-B to avoid erythema. The dosage is subsequently increased by 10–15 % as tolerated by the patient until the maximum dose of 3 J/cm2 is reached on the body and 1 J/cm2 is reached on the face. However, lower maximum doses are

D. Mehta, H. W. Lim Table 2 Narrowband ultraviolet B initial dosing and scheduling guidelines at the Department of Dermatology, Henry Ford Hospital Initial dose

Dose increase per treatment

Maximum dose (J/cm2)

I

150 mJ/cm2

10–15 % as tolerated

3 to the body and 1 to the face

II

150 mJ/cm2

10–15 % as tolerated

3 to the body and 1 to the face

III

250 mJ/cm

2

10–15 % as tolerated

3 to the body and 1 to the face

IV

250 mJ/cm2

10–15 % as tolerated

3 to the body and 1 to the face

V

400 mJ/cm2

10–15 % as tolerated

3 to the body and 1 to the face

VI

400 mJ/cm2

10–15 % as tolerated

3 to the body and 1 to the face

Start at 70 % MED

10–15 % as tolerated

3 to the body and 1 to the face

Initial dose based on skin type

Initial dose based on MED Obtain the initial MED-B

MED minimal erythema dose, MED-B minimal erythema dosing to ultraviolet B

used if the patient is unable to tolerate any further increase in dose. The maximum doses, 3 and 1 J/cm2, are recommended as there is no evidence that a further increase in dose would be associated with a better response. If treatments are missed for 1–2 days, the same dose can be administered at the subsequent treatment. A dose decrease of 33 % should be done if the patient misses 1–2 weeks of treatment, and 66 % for 2–4 weeks. NB-UVB should be reinitiated at the starting dose if more than 4 weeks of treatment are missed [10, 11, 17]. The protocol used in our center is shown in Table 2. To be prudent, we decrease the dose by 20 % for one treatment session when new lightbulbs are inserted and the unit is calibrated. Increases in dose can then be resumed based on the abovementioned protocol. NB-UVB can safely be administered daily; this is because peak UVB-induced erythema occurs at 24 h; therefore, even daily treatment would allow for evaluation of erythema from the previous treatment, and adjustment of the dose if needed. However, studies have shown no statistical significance between three or five treatments per week [10, 11, 17]. In most centers, including ours, NBUVB is administered two to three times weekly for patients’ convenience and compliance. Patients should be informed that noticeable improvement should be seen in 20–30 treatments [10, 17]. A lack of improvement after 30 treatments should lead to consideration of other forms of treatment. Treatment for NB-UVB can be continued until the patient has achieved clearance or plateauing of the response. Studies have shown that maintenance therapy prior to discontinuation resulted in a longer remission. However, it would clearly lead to a higher cumulative UVB dose. A proposed protocol for maintenance is to perform the treatment once a week for 4 weeks at the last treatment dose, then one treatment every 2 weeks at 75 % of the last treatment dose for the next 4 weeks, then one

Table 3 Dose adjustment for narrowband ultraviolet B and protocol for maintenance treatment at the Department of Dermatology, Henry Ford Hospital Dose adjustment Dosage adjustment based on missed treatments Number of treatments missed 1–2 treatments 1–2 weeks

Maintain previous dose Decrease by 33 %

2–4 weeks

Decrease by 66 %

[1 month

Restart at initial dose

[2 months

Physician assessment

Dosage adjustment based on erythema Skin assessment

Dose adjustment

No erythema

Increase dose as tolerated by patient

Mild erythema: light pink

Hold at current dose

Moderate erythema

Decrease dose by 15 %

Severe erythema/vesicles/bulla

Physician assessment

Sequential steps in the maintenance and discontinuation of treatment Twice per week for 4 weeks May continue to increase at 10–15 % as tolerated to the maximum doses (3 J/cm2 to body, 1 J/cm2 to face) Once weekly for 4 weeks

Keep at current dose

Discontinue treatment

treatment every 2 weeks at 50 % of the last treatment dose for 4 weeks, followed by discontinuation of treatment [10, 19]. At our center at Henry Ford Hospital, once the patient has achieved clearance or plateauing of response, the treatment frequency is decreased from two to three times weekly to twice weekly for 4 weeks, then once weekly for 4 weeks, followed by discontinuation of treatment (Table 3).

UVB Phototherapy for Psoriasis

2.5 Tolerability of UVB Phototherapy UVB phototherapy is safe and lacks the adverse effects of systemic immunosuppressive therapies [7, 10, 11]. Shortterm adverse effects of both BB-UVB and NB-UVB include erythema, pruritus, burning, xerosis, stinging, and occasional blistering. Similar to exposure to sunlight, reactivation of herpes simplex virus infections, though uncommon, has been reported [7, 10, 11, 25]. Long-term adverse effects of BB-UVB and NB-UVB include photoaging and a theoretical increased risk of photocarcinogenesis. However, a study that followed 3867 phototherapy patients (97 % with skin phototypes I–III) over 5 years showed that there was no significant association of non-melanoma skin cancer or melanoma with NBUVB therapy [7, 10, 21]. However, a slight increase in the number of basal cell carcinomas was noted in patients who were also treated with PUVA [21]. 2.6 Treatment of Adverse Effects Short-term adverse effects can be treated with cool compresses, topical corticosteroids, non-steroidal anti-inflammatory agents (NSAIDs) and, if severe, systemic corticosteroids [7].

3 Targeted Phototherapy Targeted UVB phototherapy is an effective treatment for localized lesions that utilizes a monochromatic xenon chloride 308 nm laser. Equipment with a polychromatic excimer lamp with a peak emission at 308 nm is also available; however, it is not widely used and is not readily available in the USA [17]. As such, the following discussion focuses on the excimer laser. 3.1 Patient Selection

treatment-resistant areas such as the elbows, knees, lower legs, and palmar and plantar lesions. It is also effective for localized lesions on the scalp [17]. 3.2 Dosing and Scheduling of Excimer Laser For thin lesions, the treatment protocol can be based on the MED to excimer laser or skin type. However, more commonly, the protocol used takes into account both skin types and the thickness of the plaques (Table 4) [10, 11, 17, 20]. If based on the MED, the dose should be increased according to degree of erythema [10, 16, 19]. Excimer laser therapy can be administered at low (0.5–1 MED), medium (2, 3, 4, or 6 MED), or high (8 or 16 MED) dose regimens. Studies have shown that the low-dose regimen did not result in clearing as effectively as the medium- or highdose regimens. The high-dose regimen had the least recurrence of symptoms but was also noted to have the highest probability of inducing blister formation [22, 23]. The dose increase during excimer laser therapy is based on the response noted (Table 5). Generally, the dose increase is between 5 and 15 %, but if there is no erythema the dose can be increased by 15–30 %. At our center, the maximum dose is 3 J/cm2 to the body and 1 J/cm2 to the face; these doses were selected as there is no evidence that higher doses would result in an improved response. Treatments are usually administered two to three times per week with an interval of 24–48 h between treatments [10, 17]. Table 5 Henry Ford Hospital protocol for dose increase for 308 nm excimer laser: dose increase per treatment Type of erythema

Dose increase

No erythema

15 % increase

Mild asymptomatic erythema

5–15 % increase

Moderate to severe erythema

Hold 1 or 2 sessions for resolution, then keep subsequent treatments at the last dose prior to the development of moderate/severe erythema

In addition to the patient criteria for NB-UVB phototherapy, targeted phototherapy is used for localized lesions and

Table 4 Henry Ford Hospital dosage and scheduling for 308 nm excimer laser: initial dosage based on skin type and plaque thickness Thick plaques (mJ/cm2)

Maximum dose (J/cm2)

Skin type

Thin plaques (mJ/cm2)

Moderately thick plaques (mJ/cm2)

I

150

200

300

3 to the body and 1 to the face

II

200

300

450

3 to the body and 1 to the face

III

250

400

600

3 to the body and 1 to the face

IV

300

500

750

3 to the body and 1 to the face

V

350

600

900

3 to the body and 1 to the face

VI

400

700

1050

3 to the body and 1 to the face

D. Mehta, H. W. Lim

3.3 Tolerability of Excimer Laser Given that the excimer laser is directed mainly towards the affected area, adverse effects are minimized and occur only on the treated area. Adverse effects include erythema, burning, hyperpigmentation, and blistering at higher fluences [18]. Long-term adverse effects are likely to be minimal as the treatment course is typically only 30–60 treatments; furthermore, non-involved skin is spared.

4 UVB Phototherapy and Combination Treatments UVB phototherapy can be combined with other treatment options to optimize psoriasis treatment for patients. This section discusses combination therapy and whether the dose of UVB phototherapy needs to be altered. 4.1 UVB Phototherapy and Topical Treatments Topical treatments are often the first-line treatment for psoriasis. UVB phototherapy is frequently used with these treatments and, in some patients, in combination with systemic agents. 4.1.1 UVB Phototherapy and Emollients Psoriatic plaques have multiple air–corneocyte interfaces that increase reflectance and cause UV rays to scatter [26, 27]. Emollients can be used to change the optics of psoriatic plaques and increase the penetration of UV light and decrease UV reflectance. The use of mineral oil and glycerol can increase UV transmission, while sunflower oil can have the opposite effect. Therefore, an effective emollient, if used, should be liquid based and have low absorptive properties. Emollients should be applied minutes before UV radiation to allow maximal saturation through the stratum corneum [26, 27]. At Henry Ford Hospital, mineral oil is applied before UVB phototherapy if scale is noted on psoriatic plaques; ointments and thick creams are avoided. 4.1.2 UVB Phototherapy and Salicylic Acid Salicylic acid absorbs in the UVB range. The application of topical salicylic acid immediately before UV treatment has been shown to decrease UV transmission and therefore should not be used. We typically ask patients to apply salicylic acid ointment at bedtime. 4.1.3 UVB Phototherapy and Topical Calcipotriene There is conflicting evidence regarding the efficacy of combination treatment of topical calciptotriene and UVB

phototherapy [28–31]. A systematic review of 11 randomized controlled trials published in 2000 showed that there is insufficient evidence to favor combination treatment of UVB phototherapy and calcipotriene [29]. However, while several studies have shown no improvement with use of calcipotriene, a recent study showed that calcipotriene use with excimer laser may improve long-term treatment efficacy and decrease cumulative laser doses [30]. Application of calcipotriene ointment has been shown to increase the MED to UVB [31]. Therefore, if a patient is using calcipotriene along with UVB phototherapy, the calcipotriene should be applied more than 2 h before the phototherapy session or after the phototherapy session [31]. 4.1.4 UVB Phototherapy and Topical Corticosteroids Topical corticosteroids in combination with UVB phototherapy do not produce an added benefit. In addition, studies have shown that the use of topical corticosteroids with UVB phototherapy may cause a higher relapse rate. Therefore, given the adverse effects associated with topical corticosteroids, they are best avoided when UVB phototherapy is used for psoriasis [32]. 4.1.5 UVB Phototherapy and Topical Retinoids Topical tazarotene in combination with UVB phototherapy works effectively in the clearance of psoriatic plaques [34]. Patients require fewer phototherapy treatment sessions, and thus are exposed to lower cumulative UVB doses. Topical tazarotene can be used daily or three times weekly [34, 35] in addition to two to three times weekly phototherapy sessions. However, application of tazarotene three times a week for 2 weeks can result in thinning of the stratum corneum and therefore increase susceptibility to UV-induced erythema. In patients already undergoing phototherapy, the UVB dose should be reduced by at least one-third when topical tazarotene is added [33, 34]. Adverse effects when using both regimens are mild irritation from the retinoid treatment. 4.1.6 UVB Phototherapy and Tar or Anthralin Anthralin or tar can also be used in combination with UVB phototherapy. However, the use of these agents can decrease UV transmission and should be removed thoroughly before exposure to phototherapy [27]. At present, this combination therapy is less frequently employed due to the messiness of either preparation and the availability of other treatment modalities [10].

UVB Phototherapy for Psoriasis

4.2 UVB Phototherapy and Systemic Treatments 4.2.1 UVB Phototherapy and Methotrexate UVB phototherapy in combination with methotrexate has a synergistic effect [33]. The combination treatment results in lower cumulative methotrexate and UVB doses being needed for clearance of psoriasis. Potential dosage regimens for UVB phototherapy and methotrexate combination treatment include: 1.

2.

Methotrexate, titrated up to 15 mg/weekly for 3–4 weeks before the start of NB-UVB three times weekly based on the protocol outlined in Sect. 2.4. Both treatments are continued until clearance of psoriasis. Methotrexate can then be gradually discontinued, and NB-UVB can be used for maintenance therapy [33, 36, 37]. Methotrexate can be started concurrently with three times weekly NB-UVB therapy based on the protocol outlined in Sect. 2.4 [38].

One of the drawbacks of the combination regimen is that recurrence or worsening of psoriatic plaques can be noted when methotrexate is discontinued. If this occurs, UVB dosage or frequency of UVB treatments can be increased; alternately, methotrexate can be tapered more slowly [33]. Because of the theoretical potential increase in photocarcinogenesis, this combination treatment should be used for the shortest treatment duration as is practical. 4.2.1.1 Contraindications to Combination Treatment Methotrexate should be used with caution in patients with a history of renal disease. It is contraindicated in patients with hepatic disease, or in those who ingest alcohol regularly. It should not be use in pregnant patients or in women planning pregnancy. 4.2.2 UVB Phototherapy and Oral Retinoids The use of UVB phototherapy and systemic retinoid treatment such as acitretin, referred to as reUVB, is an effective form of combination treatment for patients with chronic moderate to severe psoriasis, especially those with thick plaques. The use of both treatments can lower the dose of acitretin used and the frequency and dosage of the UVB treatment. The regimen to follow for the use of acitretin and UVB phototherapy is summarized below [10, 39]. ReUVB should be considered for patients with chronic moderate to severe plaque psoriasis, ineffective response to monotherapy, or limited access to phototherapy. Patients who have not been treated with reUVB should be treated with low-

dose acitretin (10–25 mg/day or 0.3–0.5 mg/kg/day) for 2 weeks before initiating phototherapy. The MED guidelines should be followed for the UVB phototherapy regimen. If skin type protocol is used as outlined in Sect. 2.4, the initial dose of phototherapy should be lowered by 30 %, given that acitretin can increase photosensitivity due to the thinning of the epidermis, hence allowing for greater penetration of UV [32, 38]. After clearance, phototherapy can be tapered as outlined in Sect. 2.4. Acitretin can then be gradually tapered and discontinued depending on the patient’s response [10, 33, 39]. Acitretin and phototherapy can also be used for palmoplantar pustular psoriasis and pustular psoriasis [40]. 4.2.2.1 Contraindications to Combination Therapy Acitretin should not be used in women of child-bearing age, and it should not be used in patients with a history of alcoholism. 4.2.3 UVB Phototherapy and Cyclosporine Long-term use of UVB phototherapy and cyclosporine is not recommended due to an increased risk of squamous cell carcinoma. Very few studies have been published on the use of cyclosporine and UVB phototherapy for a short period of time [10, 33]. 4.3 UVB Phototherapy, Biologics and Phosphodiesterase Inhibitors Treatment of psoriasis with UVB phototherapy and biologics has been shown to have a synergistic effect without changes in the adverse effect profile for either medication. In short-term studies, it has been shown that the use of TNF-a inhibitors in combination with NB-UVB phototherapy leads to a high clearance rate without increased adverse effects. Administration of etanercept 25–50 mg twice weekly with twice to three times weekly sessions of NB-UVB has been shown to initiate a quicker response. With the combination therapy, fewer phototherapy treatments and a lower dose of NB-UVB were needed to achieve improvement of psoriasis [41–44]. Adalimumab administered at 80 mg initially with 40 mg biweekly thereafter in combination with NB-UVB has also been shown to accelerate improvement in psoriasis compared with employing either treatment alone [45]. NB-UVB phototherapy has also been shown to increase the effect of ustekinumab. In a bilateral comparison study, NB-UVB was initiated on one-half of the body when patients were taking 45–90 mg of ustekinumab at weeks 0 and 4 depending on the patients’ body weight. The primary response was measured at 6 weeks and then at 12 weeks.

D. Mehta, H. W. Lim

Accelerated response was noted on the half of the body that received NB-UVB, indicating the superior efficacy of the combination therapy [46]. There is a theoretical increased risk of carcinogenesis when UVB phototherapy and biologics are used in combination for a prolonged period of time; however, there are no clear data on this at this time. Finally, two systemic medications were recently approved for treatment of moderate to severe psoriasis. Secukinumab is an anti-IL-17 monoclonal antibody, and apremilast is a small-molecule inhibitor of phosphodiesterase-4. At this time, data are lacking on the efficacy of the combination of either one with UVB phototherapy.

5 Conclusion Psoriasis is an inflammatory skin condition that affects people worldwide. A variety of treatment options such as topical treatments, phototherapy, and systemic treatments are available for psoriasis. UVB phototherapy is a mainstay of the treatment of moderate to severe plaque-type psoriasis as it is a relatively safe treatment and can easily be combined with other treatment modalities. Its limitations are access to the phototherapy site, and the time and effort needed to be put in by the patient. Compliance with Ethical Standards The authors of this article, Dhwani Mehta, MD and Henry W. Lim, MD, FAAD, have no relevant disclosures to make in regards to this article. No financial assistance was received in preparation of this article.

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