The majority of patients undergoing UV treatments are treated in the office or clinic with UVA, UVB, PUVA, Goeckerman regime, or laser treatment.
Indications for Phototherapy and/or Photochemotherapy
Atopic Dermatitis (AD)
Atopic dermatitis (or eczema) is the most common of many types of eczema; a skin disease characterized by areas of severe itching, redness, scaling, and loss of the surface of the skin; when the eruption has been present for a prolonged time, chronic changes occur due to the constant scratching and rubbing. There are periods of remissions and exacerbations. The etiology is unknown. Skin care, avoidance of substances that might irritate the skin, and ointments and creams (e.g., immunomodulators and corticosteroids) may be indicated. If these are ineffective, a physician might prescribe an oral corticosteroid or phototherapy (i.e. UVA, UVB, and/or PUVA).
The American Academy of Dermatology (AAD) published Guidelines of Care for Atopic Dermatitis, which states â€œUltraviolet (UV) phototherapy, including combination broad-band ultraviolet B (UVB)/ultraviolet A (UVA), narrowband UVB therapy, psoralen plus ultraviolet A (PUVA), and UVA1 is well established in the treatment of AD, although relapse following cessation of therapy frequently occursâ€. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) include UVA, UVB or combination of both as effective treatment for â€œmild to moderate dermatitis in older children (over 12 years old) and adults.â€ They also include PUVA as a treatment option for cases that are resistant to UV treatment alone.
A systematic review of peer-reviewed scientific literature in the Cochrane Central Register of Controlled Trials, performed by Meduri et al., found:
Three studies demonstrated that UVA1 is both faster and more efficacious than combined UVAB for treating acute AD;
Two trials disclosed the advantages of medium dose [50 J/cm(2)] UVA1 for treating acute AD; two trials revealed the superiority of combined UVAB in the management of chronic AD;
Two additional studies demonstrated that narrow-band UVB is more effective than either broadband UVA or UVA1 for managing chronic AD.
Meduri felt phototherapy with medium dose [50 J/cm (2)] UVA1, if available, should be used to control acute flares of AD while UVB modalities, specifically narrow band UVB, should be used for the management of chronic AD.
Cutaneous T-Cell Lymphomas (CTCL)
CTCLs are any of a group of T-cell non-Hodgkin lymphomas that begins in the skin as an itchy, red rash that can thicken or form a tumor. The most common types are mycosis fungoides and SÃ©zary syndrome. Mycosis fungoides affects only the skin while SÃ©zary syndrome, cancerous T-cell lymphocytes affect the skin and the peripheral blood. MF has three phases: patch, plaque, and tumor. Patch phase is flat, red and scaly, while plaque phase is thicker raised lesions, and tumor phase has larger lesions that can be shaped like a mushroom.
SÃ©zary syndrome is an advanced form of mycosis fungoides. Skin all over the body is reddened, itchy, peeling, and painful. There may also be patches, plaques, or tumors on the skin. Cancerous T-cells are found in the blood. The AAD states treatment depends on the type of CTCL, health of the patient, extent of disease, age and lifestyle. Treatments include creams and ointments to skin (e.g., cortisone, nitrogen mustard, and retinoids), oral medications (e.g., corticosteroids, retinoids, and methotrexate), phototherapy (UVB, NB-UVB, and PUVA), interferon, and radiation. The National Cancer Institute states treatment including PUVA and UVB produce remissions, however long-term remissions are uncommon, therefore most treatments are considered palliative.
Gathers et al. performed a study on 24 patients (12 stage IA, 12 stage IB) with patch stage MF to determine the effect of NB-UVB in the treatment of early stage MF and determined that NB-UVB is a viable, comparably safe, and easily administered alternative in the management of early stage MF. Outcomes from clinical trials state that NB-UVB is beneficial for the patch stage MF stating that time to complete remissions range from 6 weeks to 66 months. After complete response with PUVA, time to relapse ranges between 6 and 43 months while remission with N-UVB up to 20 months was described.
Lichen Planus (LP) is a common inflammatory disease that affects the skin, the mouth, or even the genital area with small, uncomfortable, pink or purple spots that occur mainly on the wrists, shins, lower back and genitalia. The cause of LP is unknown; however most dermatologists believe it can be classified as an autoimmune disease. It can present as reddish-purple, flat-topped bumps or white lacy appearance that may be very itchy.
The AAD states there is no cure for LP and treatment is aimed at relieving itching and in improving the appearance of the rash until it goes away. Mild cases may be treated with topical corticosteroid creams, ointments, or other anti-inflammatory drugs. Severe cases of LP may require stronger medications such as cortisone taken internally or phototherapy. Chan et al. performed a Cochrane Review and found nine randomized controlled trials that assessed the effectiveness and safety of cyclosporines, retinoids, steroids and phototherapy. The report concluded there is lack of strong evidence to support palliative treatment of LP due to small trial size, but enough evidence to justify larger trials. All treatment was reported as effective, but how effective compared to placebo was unknown. Wackernagel et al. performed a small retrospective study in 2007, which suggests phototherapy is effective in treating LP.
Morphea (localized scleroderma)
Morphea is a disorder characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissues, or both. A search of Medline database revealed the following articles. Zulian discussed the mechanism of phototherapy, methotrexate and possible future treatments. Biesla et al. discussed morphea in the deep dermis with treatment as UVA radiation, anti-inflammatory, and immunosuppressive drugs. A randomized controlled trial of 64 patients by Kreuter demonstrated the effectiveness of UVA treatment in localized scleroderma.
Parapsoriasis is a group of cutaneous diseases that can be characterized by scaly patches or slightly elevated papules and/or plaques that have a resemblance to psoriasis but are unrelated with respect to pathogenesis, histopathology, and response to treatment. Patterson discussed parapsoriasis may precede CTCL. Treatment is possible when limited to the skin, otherwise palliative. Topical treatments include steroids, nitrogen mustard, and PUVA. For advanced stages, chemotherapy and radiation is the most effective. Grema discussed the use of the excimer laser with parapsoriasis due to shorter period required for treatment and targeting individual lesions without affecting surrounding healthy skin.
Photodermatoses refers to skin disorders induced or exacerbated by light. The most common type is polymorphic light eruption, with a high prevalence of up to 10-20% in the United States. The skin might appear as spots, blisters, plaques or eczema. The exact mechanism of the diverse skin reactions to light radiation remains unclear. Treatment options include avoiding the sun, using high SPF sunscreens, topical or oral steroids. Appropriate therapy for severe cases includes phototherapy. Gambichler conducted a prospective randomized control trial comparing the effects of bath PUVA, UVA, and NB-UVB in patients with subacute prurigo. The trial revealed PUVA, UVA1 and NB-UVB appeared to be an effective and safe treatment option for patients, and UVA1 and PUVA seemed superior to NB-UVB in management of subacute prurigo.
Pityriasis lichenoides (PL)
The American Journal of Dermatology states pityriasis lichenoides is an uncommon skin condition that is difficult to diagnose and treat. It has potential to progress to cutaneous lymphoma or an ulceronecrotic presentation, which carry a risk of mortality. PL presents as pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC), and febrile ulceronecrotic Mucha-Habermann disease (FUMHD). PLEVA presents as multiple, small, red papules on the skin that develops into polymorphic lesions, with periods of remissions and periods of hyper/hypopigmentation and varicella-like scars. PLC presents as small red to brown flat maculopapules with mica-like scale with long periods of remission. FUMHD presents as generalized eruption of purpuric and ulceronecrotic plaques with systemic involvement and a mortality rate of up to 25%. The treatments for PLEVA and PLC are phototherapy, systemic antibacterials and topical corticosteroids. The treatment for FUMHD is immunosuppressant and/or immunomodulating agents, narrow-band UVB and intensive supportive care.
Pruritic eruptions of HIV disease
Pruritus is the medical term for itching. HIV is acquired human immunodeficiency virus.
Psoriasis is a chronic skin disease that appears as patches of raised red skin covered by flaky white buildup. The exact cause is unknown, but is thought to be due to an immunologic dysfunction. The most common is plaque psoriasis, which can appear on any skin surface, however the most frequent is elbows, knees, scalp, and trunk. The skin involvement can range from localized areas to generalized body involvement. The disease is lifelong and characterized by periods of remissions and exacerbations.
The National Psoriasis Foundation Medical Board has described criteria to assist medical professionals in distinguishing between mild, moderate, and severe disease based on body surface area (BSA) and impact on quality of life. Affected BSA has been frequently used to assess disease severity. One percent of BSA is approximately equal to the patients open hand with fingers tucked together and thumb tucked to the side. In clinical trials, severe disease often is commonly defined as more than 10% affected BSA, and the FDA has used 20% BSA to indicate severe disease. In 2002, the AAD published a consensus statement on psoriasis therapies that also used the mild, moderate, and severe criteria to guide treatment plans. In this system, patients with mild disease have limited BSA involvement and may be treated with topical therapies. Although moderate and severe disease categories may overlap, patients with moderate to severe disease generally have greater than 5% affected BSA, and appropriate therapies include phototherapy or systemic therapy.
Urticaria is the name of a type of pale, itchy, pink wheals on the skin that are common and are part of an allergic reaction. The AAD states it is not serious and does not usually require any treatment in most cases. However, it can be helpful to eliminate possible foods, drugs, infections, insect bites that could be the cause. A physician might prescribe oral antihistamines, topical steroids, and for systemic urticaria that persists, PUVA or other forms of treatment.
Vitiligo is a pigmentation disorder in which the skin turns white due to the loss of the skin pigment cells that produce coloration. These patches are common on the feet, face, hands and lips. The cause is unknown. The AAD states in some cases skin color returns without any treatment. Avoiding sun exposure and use of sunscreens may be adequate. Both the AAD and The National Institute of Health (NIH) state medical treatment options (under dermatologists care) include: creams and ointments to help repigment white patches (e.g., topical steroid therapy), phototherapy to repigment the skin, and/or depigmentation which involves fading the rest of the skin.
Technical literature indicates that handheld narrowband UVB (NB-UVB) delivery devices can be considered similar to conventional phototherapeutic lights since they produce wavelengths of light that are within the therapeutic range.(42) Clinical guidelines from the British Association of Dermatologists state that panel irradiators and point sources are acceptable alternatives to whole-body cabinets or upright panels, with each light source having its advantages and disadvantages. Guidelines on the treatment of psoriasis from the AAD also indicate that targeted phototherapy is an appropriate alternative to PUVA or UVB (with or without topical or oral retinoids) for the treatment of moderate to severe localized disease. Their guidelines do not recommend phototherapy for limited (mild) psoriasis, erythrodermic/ generalized psoriasis or psoriatic arthritis.
Two blinded and controlled studies compared targeted UVB with standard phototherapy of psoriasis; both used equivalent starting doses and patches matched on either side of the body. One study compared a NB-UVB lamp with cream PUVA in ten subjects with palmoplantar psoriasis. The UVB lamp and PUVA-treated sides showed similar gradual clearing over the course of 20 treatments, reaching 64% clearance at the end of the five-week treatment period. In the other blinded study, the excimer laser was compared to full body NB-UVB in 16 patients with psoriasis vulgaris. At the end of 20 treatments the psoriasis area and severity scores (PASI) were equally reduced on the two sides, from a baseline of 11.8 to 6.3 for laser and from 11.8 to 6.9 for non-targeted NB-UVB. A patch comparison in 15 patients with stable plaque also found no difference in efficacy between the 308-nm laser, the 308-nm excimer lamp, and standard TL-01 lamps.
A multicenter open trial of 124 patients with mild to moderate psoriasis reported effective clearance of lesions among the 80 patients who completed XeCl laser treatment. Comparison of these results to historical controls found laser therapy to be more effective than placebo and comparable or more effective to other standard treatments for psoriasis. Controlled studies comparing targeted phototherapy with topical treatment for patients with mild disease are lacking.
Clinical studies suggest that targeted phototherapy can be effective for treatment-resistant lesions. One controlled patch comparison reported effective clearing (PASI pre 6.2, PASI post 1.0) of treatment- resistant psoriatic lesions; six of the patients had previously received topical treatment, five had received conventional phototherapy, and three had received combined treatments including phototherapy. The same group reported that 12 of 13 subjects with â€œextensive and stubbornâ€ scalp psoriasis (i.e., unresponsive to class I topical steroids used in conjunction with tar and/or zinc pyrithione shampoos for at least one month) showed clearing following treatment with the 308-nm laser. In a recent open trial from Europe, 44 of 54 patients with palmoplantar psoriasis resistant to combined phototherapy and systemic treatments were cleared of lesions with only one NB-UVB lamp treatment per week for eight weeks.
Results suggest that targeted dosing may be more effective than dosing based on the minimal erythematic dose (MED) of unaffected skin. One study evaluated dosing in 163 patients with the XeCl laser. Initially, 120 patients with mild to moderate localized plaque were treated beginning at three times the MED of unaffected skin, increasing by one MED unless an erythematous reaction occurred on the psoriatic skin. Of the 102 patients who completed 13 treatment sessions, 87 had > 90% clearance of lesions. Based on the findings in the first treatment group, a second group of 43 patients had treatment initiated at a MED level in accordance with the epidermal thickness of the psoriatic lesion, as determined by ultrasound, to maximize therapeutic effect while minimizing adverse side effects; 34 of 40 patients (83.7%) achieved clearance of lesions in only 7.07 Â± 2.15 sessions, resulting in a lower cumulative dose of UVB. A patch comparison (described above) found no difference in efficacy between targeted laser, targeted lamp, or standard TL-01 lamps when all were administered at the standard NB-UVB dose. However, when the investigators used an accelerated dosing scheme to compare the two targeted devices (16 patients), clearance was achieved with fewer treatments and half the cumulative dose of the first regime. Thus, targeted phototherapy may allow higher (and more therapeutic) doses of light to be delivered to the lesion in comparison with dosing based on the erythematic dose of unaffected skin. Controlled studies based on the MED of the patch/lesion are needed to determine the most effective treatment and maintenance schedules.
There is concern for the possibility of cancer induction with long-term UVB treatment. PUVA has been associated with increased cancer risk; there is currently no evidence that supports increased risk following extended UVB treatment. Given the higher MED of plaques and reduced exposure of unaffected skin, targeted NB-UVB may have an improved benefit/risk ratio over non-targeted phototherapy for localized psoriasis.
There is currently no evidence to recommend any one targeted or non-targeted NB-UVB device over another. Devices with smaller focal areas may result in more frequent blistering due to â€œtiling,â€ the practice of overlapping adjoining treatment zones.
The literature supports the use of targeted phototherapy for the treatment of moderate to severe psoriasis comprising less than 20% body area for which NB-UVB or PUVA are indicated, and for the treatment of mild to moderate psoriasis that is unresponsive to conservative treatment.
Based on this review, evidence is lacking for the use of targeted phototherapy for the first-line treatment of mild psoriasis or for the treatment of generalized psoriasis, psoriatic arthritis, or other dermatologic conditions including but not limited to acne vulgaris, alopecia areata, granuloma annulare, hypertrichosis, keloids, leukoderma, rosacea, and/or warts.
Some patients require frequent treatments or live in remote locations such that office or clinic visits are not feasible. Home therapy with UVB light is an alternative. Concerns regarding over-exposure to unsafe levels of UV radiation in the home setting have been addressed with the evolution of integrated security features such as keys, pass codes etc. Nonetheless, routine clinical evaluation should be conducted to ensure that exposure is kept to the minimum level compatible with adequate control of disease and the prevention of complications.
A survey of thirty-one patients who were prescribed a home UVB phototherapy unit to treat psoriasis was performed as a pilot study of home UVB phototherapy usage; twenty-two patients responded. Generally, respondents reported home UVB phototherapy to be very helpful for their psoriasis. It was concluded that home UVB is an effective and appropriate treatment for many patients with psoriasis, but screening and education of candidates for home UVB phototherapy is important to ensure compliance with the treatment program.
Jorden et al. reported on a study of long-term modified Goeckerman regimen for psoriasis using an ultraviolet B light source in the home. Fifty-six people with extensive psoriasis began the study, fifty-five completed a modified Goeckerman program starting at one-minute exposures, with weekly increases of light by one minute until six or eight weeks of treatment had elapsed. All patients cleared of psoriasis (scalp not included). Fifty-one patients accomplished the clearance program totally in the home. Over 80% of them remain virtually clear, as they have maintained a 6- to 8-minute tar-light program two to five times a week. Thirty-seven subjects have used this home UVB unit for over a year. The authors concluded that the modified Goeckerman treatment of psoriasis in the home show that only six non-enclosed lamps were needed for the economical clearing and maintenance of many patients with psoriasis and the initial clearing rate using forty-two to sixty sub-erythemal treatments is outstanding.
Resnik and Vonderheid reported on follow-up of the original 31 patients in a ten-year study on home UV therapy for patients with mycosis fungoides. All patients used a commercially available UV phototherapy unit. Complete clinical and histologic response to home phototherapy occurred in 23 patients (74%) with a maximum duration of the response from five months to more than 15 years (median 51 months). After maintenance phototherapy was discontinued, seven patients (23%) sustained a disease free interval lasting more than 58 months (median >90 months). The authors concluded that this indicated that a cure may have been achieved in a minority of patients. Phototherapy was well tolerated without significant photo damage or photo carcinogenicity. These observations indicate that home phototherapy is a therapeutic option for treatment of selected patients with early mycosis fungoides.
The connection between skin carcinogens and PUVA has been investigated extensively. Present data appear to support a link between PUVA and an increased risk of developing melanoma as well as non-melanoma skin cancer, which also appears to persist after cessation of PUVA. Stern and colleagues prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who received 250 treatments or more.
Tanning Beds for Home Phototherapy
Non-therapeutic or cosmetic use of ultraviolet light is the use of a tanning bed. This device emits ultraviolet radiation (typically 95% UVA and 5% UVB) from fluorescent bulbs in the range of 12 to 28 100-watt lamps for home use or 24 to 60 100 to 200-watt lamps for salon use, used to produce a cosmetic tan. Even though tanning beds predominantly emit UVA, which is thought to be the least damaging of the UVA spectrum, the World Health Organization does not recommend the use of UV tanning devices because of the adverse effects (carcinogenic) on human health of overexposure to UV radiation.
In 2005, Dawe et al. conducted a paired, controlled study of 60 patients to compare NB-UVB alone versus NB-UVB plus Balneo-Phototherapy. They concluded that pretreatment with Dead Sea salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.
The Institute for Quality and Efficiency in Health Care issued a statement in February 2007 in which they describe some positive study results, but also pointed out flaws, including:
Many questions of detail are unanswered,
Dependency of therapy effect on UV spectrum is unclear,
Diversity of therapies makes summarizing difficult.
This policy was originally created in 2009; this section of the current policy has been substantially revised, and has been updated with searches of the MEDLINE database. Following is a summary of the key literature to date.
In 2011, Mudigonda and colleagues published a systematic review of literature on targeted UVB phototherapy for treating psoriasis. (47) The review included case series with at least 7 patients. A total of 9 studies meeting these criteria were identified; sample sizes ranged from 7 to 124. The authors concluded that the 308-nm excimer laser, 308-nm excimer nonlaser, and non-excimer light devices are effective for treating localized psoriasis and are safer than whole-body phototherapy because uninvolved skin is spared. The review did not pool study findings, did not evaluate separately studies by severity of psoriasis, and did not include controlled efficacy studies.
Psoralens with Ultraviolet A
One systematic review of the literature was identified, a Health Technology Assessment (HTA) from the U.K, published in 2000, on treatments for severe psoriasis. The review identified 5 randomized trials that compared psoralens with ultraviolet A (PUVA) to placebo and/or forms of phototherapy; studies were published in the 1980s or 1990s. (53) The authors of the systematic review were able to calculate differences in success rates between the treatment and control groups in only 2 of the trials; the others did not report data in such a way that these data were extractable. In a trial published in 1994 by Pai and colleagues with 24 participants, topical PUVA (applied to a bathing suit) 3 times a week resulted in a significantly greater benefit of PUVA versus placebo PUVA (risk difference [RD]: 0.67, 95% confidence interval [CI]: 0.38 to 0.96). The other trial, published by de Berker and colleagues in 1997, did not find a significant difference in success rates when PUVA twice a week was compared to psoralens plus ultraviolet B twice a week (RD: -0.12, 95% CI: -0.28 to 0.04). The authors were not able to pool the findings of any of the studies on PUVA.
More recent randomized controlled trials (RCTs) evaluating PUVA for treating psoriasis are described below:
In 2011, Amirnia and colleagues published a study from Iran in which 88 patients with moderate plaque psoriasis were randomized to receive PUVA or topical steroids. (54) Treatment was continued for 4 months or until clearance was achieved. Clearance was defined as disappearance of at least 90% of baseline lesions. All patients in both groups achieved clearance within the 4-month treatment period. Recurrence (defined as a resurgence of at least 50% of the baseline lesions) occurred significantly more often in the topical steroid group (9 of 44, 20.5%) than in the PUVA group (3 of 44, 6.8%), (p=0.007).
In 2009, Sivanesan and colleagues published a double-blind RCT evaluating the efficacy of 8-methoxypsoralen (8-MOP) PUVA treatment in patients 18 years and older with moderate to severe psoriasis affecting at least 10% of their body surface area. (55) Individuals with a history of serious side effects from oral PUVA, phototoxic reactions, or cancer; including skin cancer; were excluded. The study included 40 patients, 30 randomly assigned to receive PUVA and 10 to receive UVA plus placebo psoralens. After a washout period of 2 weeks for topical psoriasis medications and 4 weeks for phototherapy and systemic therapies, patients were treated 3 times a week for 12 weeks. A total of 28 patients completed the study, 21 in the PUVA group and 7 in the UVA plus placebo group. The primary outcome was at least a 75% improvement in the Psoriasis Area and Severity Index score (PASI 75). In an intention-to-treat analysis with the last observation carried forward to analysis at 12 weeks, 19 of 30 (63%) in the PUVA group and 0 of 10 (0%) in the UVA with placebo group achieved at least a 75% improvement in the PASI 7 score (p<0.001). In the per protocol analysis, 18 of 21 (86%) in the PUVA group and 0 of 7 (0%) in the placebo group achieved PASI 75. There were no serious adverse effects. The study found a dramatic treatment benefit with PUVA compared to UVA plus placebo; however, there was substantial drop-out and no long-term follow-up.
Two recent RCTs from India compared outcomes after treatment with oral methoxsalen PUVA or narrow-band UVB (NB-UVB). In 2011, Chauhan and colleagues included 51 patients with plaque psoriasis involving greater than 20% of their body surface area. (56) Patients received treatment with NB-UVB or PUVA 3 times a week. Treatment continued until greater than 75% clearance was attained or for a maximum of 16 weeks. A total of 43 of 51 (84%) patients completed the study. Marked improvement (>75% clearance) was seen in 17 of 21 (90.9%) study completers in the NB-UVB group and 18 of 22 (81.8%) in the PUVA group; p>0.05. The mean time to achieve results was also similar in the 2 groups, a mean of 9.9 weeks with each treatment. A 2010 study by Dayal and colleagues randomly assigned 60 patients with chronic plaque psoriasis to receive twice weekly PUVA (n=30) or twice weekly NB-UVB phototherapy (n=30). (57) After the 3-month treatment period, all patients in both groups had at least 75% clearance of psoriasis or complete clearance. The PASI score did not differ significantly between groups (mean of 1.39 in the PUVA group and 1.61 in the NB-UVB group). The mean number of treatments to achieve clearance, however, was significantly higher in the NB-UVB group than the PUVA group, 16.4 and 12.7, respectively.
No studies were identified that compared home-based PUVA to office-based PUVA. A 2010 review of various types of home phototherapies for psoriasis did not discuss any studies on PUVA delivered at home. (58)
Targeted phototherapy describes the use of ultraviolet light that can be focused on specific body areas or lesions. The literature supports the use of targeted phototherapy for the treatment of moderate to severe psoriasis comprising less than 20% body area for which NB-UVB or PUVA are indicated, and for the treatment of mild to moderate localized psoriasis that is unresponsive to conservative treatment. Based on this review, evidence is lacking for the use of targeted phototherapy for the first-line treatment of mild psoriasis or for the treatment of generalized psoriasis or psoriatic arthritis.
Multiple RCTs have evaluated PUVA for treating severe psoriasis. Among recent trials (2009 or later), one study found significantly greater benefit with PUVA compared to ultraviolet A (UVA); this study was limited by a high drop-out rate. Two recent RCTs from India found similar benefit of PUVA and NB-UVB. In addition, PUVA for severe treatment-resistant psoriasis is well-accepted and is recommended by the American Academy of Dermatology. One 2011 RCT from Iran focusing on patients with moderate psoriasis showed similar benefits with PUVA and topical steroids and a lower rate of recurrence in the PUVA group; this study is insufficient to draw definitive conclusions about the efficacy of PUVA in this patient population. There is a lack of evidence that home-based PUVA for treating psoriasis is as safe or effective as office-based treatment.
Practice Guidelines and Position Statements
American Academy of Dermatology: Their 2010 Guidelines on the management of psoriasis state that targeted phototherapy with the monochromatic xenon-chloride excimer laser can clear psoriasis but that there is limited information on the optimal dosage, scheduling of excimer laser therapy, and duration of remission. (38) Recommendations on PUVA are as follows:
Systemic PUVA with ultraviolet A is indicated in adults with generalized psoriasis who are resistant to topical therapy.
There are no studies in children; systemic PUVA may be used with caution in individuals less than 18 years.
Systemic PUVA is contraindicated in patients with known lupus erythematosus, porphyria or xeroderma pigmentosum.
Caution is recommended for several groups of patients including those with skin types I and II, and pregnant and nursing women.
In 2010, Whitton and colleagues published a Cochrane review of randomized controlled trials (RCTs) on treatments for vitiligo. (61) The investigators searched the literature through November 2009 and identified 5 trials on excimer laser therapy. None of these trials included a control group of individuals who did not receive excimer therapy, so the effect of laser therapy cannot be isolated. Four trials compared the combination of excimer laser therapy and a topical therapy to excimer lasers alone or excimer lasers plus a placebo topical treatment. The fifth trial compared different frequencies of excimer laser treatment (once, twice, or three times weekly). The Cochrane investigators did not pool findings of the studies on laser therapy for vitiligo.
In order to adequately evaluate the impact of laser treatment or other targeted phototherapy treatment on vitiligo, RCTs are needed that include a comparison group of patients who receive a treatment other than targeted phototherapy (i.e. an alternative treatment, no treatment, or sham treatment). Two RCTs of this type have been published by the same research group in Italy, and their findings are described below. These trials were not included in the Whitton et al. Cochrane review.
In 2012, Nistico and colleagues published a non-blinded RCT that included 53 patients with localized and generalized vitiligo. (62) Patients were randomly assigned to one of 3 treatments for 12 weeks: 1) Excimer laser plus vitamin E (n=20); 2) excimer laser plus topical 0.1% tacrolimus ointment and vitamin E (n=20); 3) vitamin E only (control group, n=13). All patients in the 2 excimer laser groups completed treatment; 1 patient in the control group dropped out. Before and after treatment, 2 independent clinicians rated clinical response; 51-75% repigmentation was considered a â€˜goodâ€™ response and >75% repigmentation was considered an â€˜excellentâ€™ response. The proportion of patients with a good or excellent response was 11/20 (55%) in the laser plus vitamin E group, 14/20 (70%) in the laser E plus tacrolimus plus vitamin E group, and 0 in the control group. The rate of good or excellent response did not differ significantly between the groups that received excimer laser therapy with and without topical treatment (p=0.36). The response rate was significantly better in both groups receiving laser treatment compared to the control group (p<0.001).
The Italian research group also published a similar 12-week study in 2009 in which topical 4% khellin ointment was used instead of tacrolimus ointment. (63) This study included 48 patients (16 per group), of which 45 (94%) completed treatment. The proportion of patients with a good or excellent response (see definitions above) was 14/16 (88%) in the excimer laser plus vitamin E group, 14/16 (88%) in the excimer laser plus khellin plus vitamin E group, and 1/16 (6%) in the vitamin E only (control) group. The clinical response rates in the 2 groups receiving laser treatment were significantly higher than in the control group.
Psoralens with Ultraviolet A (PUVA)
The 2010 Cochrane review of trials on treatments for vitiligo, discussed above in the section on targeted phototherapy, identified 10 RCTs evaluating oral PUVA. (61) Two trials assessed oral PUVA alone, and 8 assessed PUVA in combination with other treatments e.g., calcipotriol, azathioprine, polypodium leucotomos, khellin, or surgical treatment. Seven of the 8 studies used 9 methoxypsoralen. Six trials were identified on oral PUVA plus sunlight; 2 of these used placebo as the comparison. Due to differences among studies, findings of trials on oral PUVA and on oral PUVA plus sunlight were not pooled.
An earlier meta-analysis of treatments for vitiligo was published in 1998 by Njoo and colleagues. (64) A pooled analysis of 2 RCTs on oral unsubstituted psoralen plus sun for generalized vitiligo (total n=97) found a statistically significant treatment benefit of active treatment compared to placebo (pooled odds ratio [OR]: 19.9, 95% confidence interval [CI]: 2.4 to 166.3). A pooled analysis of 3 RCTs, 2 on oral methoxsalen plus sun and 1 on oral trioxsalen plus sun (total n=181) also found a significant benefit of active treatment versus placebo on generalized vitiligo (OR: 3.8, 95% CI: 1.3 to 11.3). All studies were published prior to 1985, had relatively small sample sizes (confidence intervals were wide), and used sun exposure rather than artificial UVA.
One recent RCT, using a psoralen formulation available in the U.S. was published in 2007 by Yones and colleagues. (65) The study used data on 56 patients in the U.K. who had non-segmental vitiligo. Outcome assessment was blinded. Patients were randomly assigned to receive twice-weekly treatments with methoxsalen hard gelatin capsules (8-MOP) psoralen plus UVA (n=28) or narrow band (NB)-ultraviolet B (UVB) therapy (n=28). The NB-UVB treatments were administered in a Waldmann UV500 cabinet containing 24 Phillips 100 NB-UVB fluorescent tubes. In the PUVA group, the starting dose of irradiation was 0.5 J/cm2, followed by 0.25 J/cm2 incremental increases if tolerated. Patients were evaluated after every 16 sessions and followed for up to 1 year. Treatment was discontinued if there was complete or near complete resolution of vitiligo, no or minimal improvement after 32 treatments, completion of 200 lifetime treatments, or upon patient request. All patients were included in the analysis. The median number of treatments received was 49 in the PUVA group and 97 in the NB-UVB group. At the end of treatment, the median improvement body surface area with vitiligo (BSA-V) was 23% in the PUVA group and 61% in the NB-UVB group. In addition, 5 of 25 (20%) of patients in the PUVA group and 8 of 25 (32%) in the NB-UVB group had at least 75% improvement in BSA-V at the end of follow-up. The authors did not provide p-values in their outcome table. They stated though, that the difference in improvement in BSA-V did not differ significantly between groups. A total of 24 (96%) patients in the PUVA group and 17 (68%) in the NB-UVB group developed erythema at some point during treatment; this difference was statistically significant, p=0.02.
Light therapy for vitiligo includes both targeted phototherapy and PUVA. Most published RCTs evaluating targeted phototherapy for vitiligo treated patients in all groups with targeted phototherapy and thus the effect of phototherapy treatment cannot be isolated. There are 2 small RCTs, both from the same research group, which found that excimer laser treatment produced better results than a vitamin E control group. British guidelines on vitiligo do not specifically address targeted phototherapy. There is insufficient evidence that targeted phototherapy is effective compared to more conservative treatments or no treatment/placebo, and it is therefore considered experimental, investigational and unproven.
There is some evidence from randomized studies, mainly those published prior to 1985, that PUVA is more effective than placebo for treating vitiligo. PUVA for vitiligo is recommended in British guidelines for adults who do not respond to more conservative treatments. Based on the available evidence and clinical guidelines, PUVA may be considered medically necessary in patients with vitiligo who have not responded adequately to conservative therapy.
Practice Guidelines and Position Statements
In 2008, a guideline on the diagnosis and management of vitiligo was published by several organizations in the U.K. including the British Association of Dermatologists, the Royal College of Physicians of London, and the Cochrane Skin Group. (66) The guideline included the following statements:
PUVA therapy should be considered for treatment of vitiligo only in adults who cannot be adequately managed with more conservative treatments. PUVA is not recommended in children. (Grade of recommendation D, Level of evidence 4)
If phototherapy is to be used for treating nonsegmental vitiligo, NB-UVB should usually be used in preference to oral PUVA. (Grade of recommendation A, Level of evidence 1+)
A trial of PUVA therapy should be considered only for adults with widespread vitiligo, or localized vitiligo associated with a significant impact on patient's QoL (quality of life). Ideally, this treatment should be reserved for patients with darker skin types. (Grade of recommendation D, Level of evidence 3)
Before starting PUVA treatment, patients should be made aware that there is no evidence that this treatment alters the natural history of vitiligo. They should also be made aware that not all patients respond, and that some body sites, such as the hands and feet, respond poorly in all patients. They should also be informed of the limit to the number of treatments due to possible side-effects. (Grade of recommendation D, Level of evidence 3)
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