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Background
Psoriasis is a chronic skin disease that generally appears as patches of raised red skin covered by a flaky white buildup. Although the exact cause is unknown, psoriasis is thought to be due to an immunologic dysfunction, which accelerates the growth cycle of skin cells, causing them to accumulate faster than they can be shed.
Approximately 80 percent of persons with psoriasis have "plaque psoriasis". Plaque psoriasis can appear on any skin surface, although the knees, elbows, scalp, trunk and nails are the most common locations. There are several other types of psoriasis, and between 10 percent and 30 percent of people with psoriasis also develop psoriatic arthritis.
Treatments for psoriasis can be divided into three basic categories: sunlight and topical agents (corticosteroids, calcipotriene, anthralins, tazarotene, coal tar, salicylic acid, moisturizers); phototherapy (broad-band UVB, PUVA); and systemic medications (methotrexate, oral retinoids, cyclosporine).
Excimer lasers [XTRAC Excimer Laser Treatment System, (PhotoMedex, Carlsbad, CA) and EX-308 Excimer Laser System (Ra Medical Systems, Carlsbad, CA)] have been cleared by the FDA based on 510(k) applications for treatment of mild to moderate localized psoriasis. Both the XTRAC and the EX-308 are handheld laser devices that use xenon chloride sources and provide intense, targeted UVB light. The potential benefits over standard UVB treatments are in terms of more rapid clinical response and more targeted therapy, avoiding the side effects of ultraviolet light exposure to unaffected skin. This procedure is usually repeated at least twice a week for 2-4 weeks.
There is evidence from controlled clinical trials of the effectiveness of excimer laser treatment of mild to moderate psoriasis. However, the comparative effectiveness of topical and laser treatment of psoriasis is unknown because these treatments have not been directly compared in a prospective clinical study. In addition, there is no adequate evidence of the effectiveness of laser therapy in combination with topical therapy. There is also limited evidence of the durability of the response to laser treatment of psoriasis. There is some evidence that a significant proportion of patients with psoriasis that is refractory to topical therapies may respond to laser treatment.
Asawanonda, et al., 2000 reported on a dose response study involving 13 patients with psoriasis plaques. Varying numbers of excimer pulses were delivered at fixed doses with a range of fluences from suberythemogenic to supraerythemogenic. Lesions remained in remission with as few as a single high fluence (up to 16 times the minimal erythemogenic dose (MED)) treatment, whereas recurrences occurred in lesions treated with multiple doses of lower fluences shortly after cessation of treatment. The duration of remissions seen with the high fluences was 6.5 months. Based on these findings, the authors stated that "[w]e speculate that the ideal approach for localized, limited plaques may well be single or at most a few 'high-dose' treatments, whereas for widespread psoriasis several 'medium-dose' treatments may make more sense" (Asawanonda, et al., 2001).
Feldman, et al. (2002) reported on a multicenter study of the excimer laser involving 124 patients with stable mild-to-moderate plaque-type psoriasis, 32 of whom dropped out of the study before completing the course of treatment. Patients were scheduled twice weekly for a total of 10 treatments. Seventy-two percent of patients who completed the treatment course achieved at least 75% clearing in an average of 6.2 treatments. Eighty-four percent of patients reached improvement of 75% or better after 10 or fewer treatments. Side effects included erythema in half of the 124 patients, blisters in 56%, hyperpigmentation in 47%, and erosion in 31%. Other side effects included pain, sunburn sensation, scaling, itching, tenderness, flaking, peeling, vesicles, disease flare, scab, and weeping lesions. The authors concluded that the excimer laser appears to be safe and effective for psoriasis, and has an advantage over conventional photochemotherapy in that it requires fewer visits and targets only the affective areas of skin, sparing the surrounding uninvolved skin.
Trehan and Taylor (2002) reported on a self-controlled study involving 16 patients with multiple stable psoriasis plaques who were treated with the excimer laser. Two plaques were selected on each patient, and half of each plaque was treated with a single excimer laser dose, whereas the other half (control) was left untreated. Eleven patients showed significant improvement with reduction of the plaque to a flat red macule within treated sites within one month. There was no change in the control halves of the psoriatic plaques. At baseline, the mean Psoriasis Area and Severity Index (PASI) score was 6.31, but 4 weeks after a single treatment the mean modified PASI score was 3.56 (p < 0.01).
Gerber, et al. (2003) reported on the effectiveness of the excimer laser in an uncontrolled study involving 120 patients with chronic plaque psoriasis, 102 of whom completed the study. Patients were treated twice a week for the first 3 weeks, then once a week until clearance was achieved. Of these patients, two-thirds had a 90% or greater improvement in PASI score after a maximum of 10 treatments, and 85% had 90% or greater improvement in PASI score after a maximum of 13 sessions. Blistering occurred at least once in 40% of the patients, and 26% in this group had erosions and pain. Duration of remission was not reported.
Taneja, et al. (2003) reported on a before-and-after study of excimer laser therapy in 18 subjects with recalcitrant plaque psoriasis that had not responded to other treatments, four of whom dropped out before the end of the study. Patients were treated twice a week. Forty-four plaques were treated with the excimer laser, and one lesion in each subject was left untreated as a control. Plaques received a mean of 10 treatments (range, 4-14). The mean PASI scores of the treated plaques decreased from 6.2 before treatment to 1.2 after treatment 10, whereas the mean PASI scores of the untreated plaques increased from 6.4 before treatment to 6.9 after 10 treatments. At follow-up, the mean modified PASI scores of all treated lesions gradually regressed from 1.0 at the time of the last treatment; to 2.0 by the end of the third month; to 3.1 at the 6-month follow-up. The relapse was mild in all cases and mostly focal in 20 of 44 cases.
Thus, the excimer laser may be considered as a treatment option for those patients in whom topical therapy has failed. According to published clinical studies, responses increase with up to 13 treatments, and the typical duration of response is 4 to 6 months. Additionally, clinical trials of the laser therapy selected patients with less than 10% of body surface area affected because, in the clinical setting, it is not practical to treat more than 10% of body surface area with the laser, because of the extended treatment time required due to the relatively small treatment spot size.
There is also adequate evidence that pulsed dye laser (PDL) is effective in the treatment of psoriasis (Ros et al, 1996; Zelickson et al, 1996; Lanigan et al, 1997; Taibjee et al, 2005; Erceg et al, 2006; Ilknur et al, 2006; de Leeuw et al, 2006; Bovenschen et al, 2007). It should be noted that the National Psoriasis Foundation (2007) states that PDL can be used to treat chronic localized plaque lesions.
Ros et al (1996) used the flash-lamp-pumped PDL, which selectively damages dermal vessels, to treat psoriatic plaques and evaluated the role of the vasculature in the therapeutic response. A total of 10 patients with psoriasis were treated with the PDL on single, stable psoriasis plaques. Treatments varied between one and three times, and the lesional response was graded using a scale for erythema, scaling, and infiltration. Six of 10 patients experienced a beneficial clinical effect after therapy. The psoriasis severity scale in these patients was reduced to 2.2 +/- 1.3 compared with a 7.2 +/- 1.7 grade for control areas. The plaques readily developed crusting with therapy, with one leg lesion healing with atrophy. Histopathology in 3 patients immediately after therapy showed no epidermal damage. One week after laser therapy, the necrotic former epidermis was apparent in superficial crusting. Epidermal thinning and regeneration was seen without any signs of psoriasis. The authors concluded that PDL therapy may improve plaque psoriasis; and this improvement may be related to the role the microvasculature plays in psoriasis.
Zelickson and co-workers (1996) examined the clinical and histological events of psoriasis treated with the PDL. Psoriatic plaques were treated with a short (450 microseconds) and long (1500 microseconds) pulse-width PDL. Photographs of the plaques were used for clinical assessment. Biopsy specimens were examined microscopically. Significant clinical improvement was seen, and no significant difference between the short and long pulse-width PDL was observed. Patients responding to treatment with the PDL remained in remission for up to 13 months. Histological normalization occurred after treatment. Two pre-treatment vascular patterns were seen: (i) vertically oriented vessels with few horizontal vessels, and (ii) numerous tortuous vessels. Tortuous vessels were associated with poor clinical results. The authors concluded that the PDL can induce prolonged remission in chronic plaque psoriasis; and the vascular pattern may help to distinguish those patients likely to respond to this treatment.
Taibjee and colleagues (2005) noted that the excimer laser delivers high energy monochromatic ultraviolet (UV) B at 308 nm. Advantages over conventional UV sources include targeting of lesional skin, reducing cumulative dose and inducing faster clearance. Studies of the PDL in psoriasis reported between 57 % and 82 % response rates; remission may extend to 15 months. These investigators examined excimer laser and PDL in the treatment of psoriasis. They conducted a within-patient controlled prospective trial of treatment of localized plaque psoriasis. A total of 22 adult patients, mean Psoriasis Area and Severity Index (mPASI) 7.1, were recruited. Fifteen patients completed the full treatment, of which 13 were followed-up to 1 year. Two selected plaques were treated with excimer twice weekly and V Beam PDL, pre-treated with salicylic acid (SA), every 4 weeks, respectively. Two additional plaques, treated with SA alone or untreated, served as controls. The primary outcome measures were: (i) changes in plaque-modified Psoriasis Activity and Severity Index (PSI) scores from baseline to end of treatment; (ii) clinical response to treatment (CR(T)), assessed by serial photographs; (iii) percentage of plaques clear at the end of treatment; and (iv) percentage of plaques clear at 1-year follow-up. The secondary outcome measures were: (i) number of laser treatments to clearance; (ii) time to relapse; (iii) frequency of side-effects; and (iv) qualitative observations with SIAscope. The mean improvement in PSI was 4.7 (SD 2.1) with excimer and 2.7 (SD 2.4) with PDL. PSI improvement was significantly greater in excimer than PDL (p = 0.003) or both control plaques (p < 0.001). CR(T) indicated 13 patients responded best with excimer, 2 patients best with PDL, and in 7 patients there was no difference between the two lasers. CR(T) was significantly greater for excimer than PDL (p = 0.003) or both controls (p < 0.001). CR(T) was also significantly greater for PDL than SA alone (p = 0.004) or untreated control (p = 0.002). Nine (41 %) patients cleared with excimer, after mean 8.7, median 10 weeks treatment. Seven of these 9 patients were followed-up to 1 year; 4 remained clear, 2 relapsed at 1 month, and 1 at 6 months. Six (27 %) patients cleared with PDL, after mean 3.3, median 4 treatments. All 6 patients were followed-up to 1 year; 4 remained clear, 1 relapsed at 4 months and 1 at 9 months. Despite common side-effects including blistering and hyper-pigmentation, patient satisfaction was high. Serial images obtained with the SIAscope during treatment indicated different mechanisms of action of the two lasers. The authors concluded that excimer and V Beam PDL are useful treatments for plaque psoriasis. Although the excimer appears to be on average more effective, a subset of patients may respond better to PDL; and long-term remission is achievable with both lasers.
Erceg and colleagues (2006) compared the effectiveness of the PDL in the treatment of localized, recalcitrant plaque psoriasis with a potent topical therapy, using calcipotriol/betamethasone dipropionate (Dovobet) as an active comparator. A total of 8 patients with psoriasis were treated with both PDL (585 nm) and calcipotriol/betamethasone dipropionate in an open, intra-patient, left-right comparison. A plaque severity score (sum score) and photographs were used to document the course of therapy. Patients reported pain on a visual analogue scale. Both treatments were well- tolerated, although 1 patient left the study due to post-PDL treatment pain. A significant difference in the sum score 12 weeks after treatment was seen in favor of the PDL (62 % versus 19 % reduction; p < 0.05). Scores for erythema declined significantly at week 12 in both the PDL and the calcipotriol/betamethasone dipropionate group (p < 0.001). Induration and desquamation scores were significantly reduced at week 12 in the PDL group, without a statistically significant reduction in calcipotriol/betamethasone-treated lesions. The pain scores declined with progressive PDL treatments, although not statistically significantly. The authors concluded that PDL treatment might be considered for the treatment of localized, recalcitrant plaque psoriasis, when other topical therapies have failed.
Ilknur et al (2006) compared the effectiveness of the PDL treatment with that of clobetasol propionate treatment. A total of 21 patients with chronic, stable psoriatic plaques that involved less than 20 % of their body were included in the study. Three similar-appearing psoriasis plaques in these patients were selected. Whereas the 1st plaque received only PDL, the 2nd plaque received PDL after salicylic acid, and the 3rd plaque received clobetasol propionate ointment and salicylic acid. Evaluation of the study plaques was carried out by the mPASI score and by measuring the area of the plaques. Of the 21 patients, 19 completed the study. Although the decrease in mPASI scores was determined to be maximum for clobetasol propionate + salicylic acid-treated plaques and minimum for only PDL-treated plaques, the decrease was statistically significant in all groups when compared with baseline (p < 0.003). At the 3- and 6-week evaluations, there was a statistically significant difference between clobetasol propionate + salicylic acid-treated plaques and the two PDL-treated plaques (p < 0.003); however, the difference observed at the 9-, 12-, and 15-week evaluations was statistically significant only between clobetasol propionate + salicylic acid-treated plaques and PDL-treated plaques (p < 0.003). When the baseline and 15-week evaluations were compared, there was no statistically significant increase in the mean lesion areas of clobetasol propionate + salicylic acid-treated psoriatic plaques (p > 0.003), but there was a statistically significant increase in the mean lesion areas of two PDL-treated psoriatic plaques (p < 0.003). The authors concluded that the results of this study showed that the effect of PDL could be increased when salicylic acid was added to treatment, although there was no statistically significant difference between both treatment protocols. However, clobetasol propionate + salicylic acid treatment is more effective than both PDL and PDL + salicylic acid treatment.
de Leeuw et al (2006) prospectively assessed the safety and effectiveness of PDL treatment of psoriasis of the hands and feet. A total of 41 patients with therapy-resistant psoriasis of the hands and feet were treated once every 4 to 6 weeks with PDL at 585-nm wavelength, 450-microsecond pulse duration, 7-mm spot diameter, and 5- to 6.5-J/cm2 fluence. Calcipotriol ointment and salicylic acid 5 % to 10 % ointment were used as keratolytic agents. Treatment effectiveness was evaluated by blinded comparison of photographs of the lesions taken before and after PDL treatment in each patient. A good to very good improvement in the lesions was observed in 76 % of the patients after treatment. An average duration of remission was 11 months. Side effects were transient purpura, moderate discomfort during the treatment, transient hyper-pigmentation or hypo-pigmentation, and incidental transient crustae. The authors concluded that concomitant treatment with PDL and topical calcipotriol, salicylic acid, or both was a satisfactory modality for treating psoriasis of the hands and feet. There was a subjective improvement in the symptoms and quality of life in all patients.
Bovenschen and colleagues (2007) reported that after 8 weeks of follow-up, PDL treatment for localized and recalcitrant plaque psoriasis resulted in persistent reductions of activated and memory effector T-helper cells in the dermis, cytotoxic T cells in the epidermis, and normalization of epidermal proliferation and keratinization, in contrast to treatment with calcipotriol/betamethasone dipropionate ointment.
In summary, direct comparative studies have shown the excimer laser to be more effective than the pulsed dye laser for psoriasis (Taibjee, et al., 2005). However, the pulsed dyle laser requires fewer treatments and has fewer side effects. The pulsed dye laser target a different part of the psoriasis pathway than the excimer laser, with the pulsed dye laser targeting the abnormal microvasculature of psoriatic plaques. Because of its different target, it has been suggested that the pulsed dye laser may be useful in excimer-laser–resistant cases (Hruza, 2005), as some patients who do not respond to the excimer laser have been shown to respond to the pulsed dye laser.
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