Efficacy of localized phototherapy and photodynamic therapy for psoriasis: a systematic review and meta-analysis

REVIEW ARTICLE

Efficacy of localized phototherapy and photodynamictherapy for psoriasis: a systematic review andmeta-analysisFahad Almutawa1, Lukman Thalib2, Daniel Hekman3, Qing Sun4, Iltefat Hamzavi5 & Henry W. Lim5

1Department of Medicine, Facultyof Medicine, Kuwait University,Al-jabriya, Kuwait.2Department of CommunityMedicine (Biostatistics), Facultyof Medicine, Kuwait University,Al-jabriya, Kuwait.3Grand Rapids Medical EducationPartners, Grand Rapids, MI, USA.4Department of Dermatology,Qilu Hospital of ShandongUniversity, Jinan, China.5Department of Dermatology,Henry Ford Hospital, Detroit, MI,USA.

Key words:excimer; localized NB-UVB;photodynamic therapy; targetedUVB phototherapy; topical PUVA

Correspondence:Dr Fahad Almutawa, MD,Department of Medicine, Facultyof Medicine, Kuwait University,Al-jabriya, Kuwait.Tel: +965-25319596Fax: +965-25338907e-mail:[email protected]

Accepted for publication:21 November 2013

Conflicts of interest:None declared.

SUMMARYLocalized phototherapy including topical psoralen plus ultraviolet A (PUVA)and targeted ultraviolet B (UVB), and photodynamic therapy (PDT) havebeen increasingly used in the treatment of localized psoriasis. Yet, there are nosystematic reviews or meta-analyses that scientifically evaluated the pooledefficacy of these treatments in psoriasis. We searched Medline, Embase, andCochrane databases during the period of January 1980 to June 2012. Oursystematic search resulted in 765 studies, 23 of them were included in thereview. The primary outcome was 75% reduction in severity score from base-line. A meta-analysis using random effect model found topical PUVA to bemore effective than non-laser targeted UVB [odds ratio: 3.48 (95% confidenceinterval 0.56–21.84), P = 0.183]. The pooled effect estimate of the efficacy(75% reduction in severity score) of topical PUVA, targeted UVB, and PDTwere as follows: 77% (topical PUVA), 61% (targeted UVB), and 22% (PDT).Topical PUVA and targeted UVB phototherapy are very effective in the treat-ment of localized psoriasis. Topical PUVA seems more effective than non-lasertargeted UVB phototherapy. On the other hand, PDT has low efficacy andhigh percentage of side effects in treating localized psoriasis.

Photodermatol Photoimmunol Photomed 2014; ••: ••–••

Photodermatology, Photoimmunology & Photomedicine

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltddoi:10.1111/phpp.12092

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Psoriasis is a chronic inflammatory disease that affects theskin and/or the joints with a worldwide prevalence thatranges from 0.6% to 4.8% (1). Treatment of psoriasis de-pends on the severity of the disease. The majority of pso-riatic patients present with mild or localized disease thatcan be treated with topical medications such as corticos-teroids, vitamin D analogs, retinoids, anthralin, or tar (1).

When these topical treatments are found to be ineffective,the next level of therapy entails the use of phototherapy,systemic medications, or biologics. Of these, phototherapyremains an attractive option because of its efficacy andcost effectiveness (2).Localized phototherapy offers theadvantage of subjecting skin lesions to significantly highdoses of radiation while sparing nearby uninvolved skin (3).Targeted ultraviolet B (UVB) phototherapy [excimer(308-nm) laser, excimer (308-nm) light, and localized nar-rowband (NB)-UVB (311–313-nm) light], topical psoralenplus ultraviolet A (PUVA), and photodynamic therapy(PDT) are localized forms of phototherapy that have beenused to treat psoriatic lesions not responding to topicaltreatments. For simplicity and clarity, treatments usingUVB and those using PUVA photochemotherapy are col-lectively referred to as ‘phototherapy’ in this study.

Despite the ever increasing use of localized phototherapyto treat psoriasis, the research evidence to support theseclinical practices arises from a handful of relatively smallclinical trials and a number of nonrandomized case series.Moreover, findings from these underpowered studies,which represented the best available data, formed the basisof recommendation from the American Academy of Der-matology. These recommendations included the use of tar-geted UVB phototherapy for pediatric and adult psoriasiswith less than 10% body surface area involvement andtopical PUVA for adult psoriasis on the palms and soles(2).There are no systematic reviews or meta-analyses thatpooled or evaluated the efficacy of these localized forms ofphototherapy.

In this study, we aimed to conduct a systematicreview and meta-analyses to provide a pooled estimate ofthe efficacy and short-term safety of targeted UVBphototherapy(including excimer (308-nm) laser, excimer(308-nm) light, and localized NB-UVB (311–313-nm)light), topical PUVA, and PDT in the treatment of local-ized plaque psoriasis including palmoplantar psoriasis. Wealso performed a meta-analysis of all published clinicaltrials that compared the UVB to PUVA.

METHODS

We searched Medline, Embase, and Cochrane databasesduring the period of January 1980 to June 2012. The key

words were ‘psoriasis’ in combination with all of the fol-lowing words: excimer laser, excimer light, 308 nm, tar-geted ultraviolet B, targeted UVB, targeted phototherapy,localized UVB, localized phototherapy, topical psoralenand ultraviolet A, topical PUVA, cream PUVA, gel PUVA,lotion PUVA, paint PUVA, soak PUVA, photodynamictherapy, and PDT. The search was limited to clinical trialsperformed in humans and reported in English literature.

The eligible studies were randomized and nonran-domized clinical trials as well as case series that evaluatedthe efficacy of targeted UVB phototherapy, topical PUVA,and PDT in the treatment of plaque psoriasis. Our primaryoutcome was the percentage of patients who showed atleast 75% reduction in their severity score. However, thescoring system of localized treatments usually focuses onlesions on one area of the body. As such, it is different fromthe same scoring system used to assess the response to theentire body in systemic therapy. Our secondary outcomewas the side effects, including painful erythema and blis-tering from studies evaluating targeted UVB phototherapyand topical PUVA as well as pain from studies evaluatingPDT.

Because phototherapy alone is not the optimal treatmentfor pustular, guttate, and erythrodermic psoriasis, weexcluded these subtype of psoriasis from our search. Wealso excluded all UV-based phototherapy delivered to theentire body surface. Studies that did not report the per-centage of patients achieving 75% improvement andstudies without adequate description of the treatmentprotocol were also excluded. Case series with less than 10patients were excluded as well.

Two of the authors (F. Almutawa and D. Heckman)assessed the eligibility of the studies and extracted the fol-lowing data from the original articles: authors, year,method, number of patients, types of targeted photo-therapy, treatment protocol, outcome, adverse effects, andnumber of withdrawals. The quality of the randomizedclinical trials were assessed by the Jadad scoring systemusing a 0–5 score that assessed the randomization, blinding,and withdrawals; a higher score indicates data of higherquality (4).

STATISTICAL ANALYSES

Our primary outcome was 75% reduction in psoriasisfrom the baseline. Our analyses composed of two steps.The first step was meta-analysis of randomized controlstudies that compared topical PUVA vs. targeted UVBphototherapy. We combined these studies to compute theodds ratio (OR) and 95% confidence level for the primaryoutcome. We evaluated the heterogeneity between the

Almutawa et al.

Photodermatol Photoimmunol Photomed 2014; ••: ••–••© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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studies using Cochrane Q statistics and I2. We used thefixed effect meta-analytical model in the absence of signifi-cant heterogeneity between studies. When significant het-erogeneity was identified, we used random effects model toobtain the pooled estimate, as per the widely used recom-mendations of the Cochrane Collaborations (5). Metaanalyses were done using Comprehensive Meta Analysesprogram (6). We plotted the individual study estimatesand overall pooled estimates in a forest plot. On the basisof the pooled risk estimate, we computed the numberneeded to treat.

The second step of our analysis was to quantify thepatient outcome, defined by a 75% reduction in psoriasisscore after each of the phototherapy and PDT treatment.We computed the pooled weighted estimates of each treat-ment separately using all available research publications,including randomized and nonrandomized studies. Wealso plotted the individual study estimates and overallpooled estimates with interval measures. To obtain thepooled estimates of each of the therapies, MetaXL(MetaXL, version 1.3, 2012; EpiGear, Wilston, Queens-land, Australia) was used.

Because of insufficient reported data, we were unable tocarry out all subgroup comparisons and sensitivity analysesthat we initially intended to do. However, there were asufficient number of studies to perform subgroup analysisof the three different modalities of targeted UVB, namely,excimer (308-nm) laser, excimer (308-nm) light, andNB-UVB (311–313-nm) light. We also performed a sub-group analysis to compare the different treatment protocolsbased on the starting dose and the frequency of treatment.

RESULT

Our systematic search resulted in 765 studies, 23 of themmet the inclusion criteria and were included in the system-atic review (Fig. 1). Of the 23 studies, 13 evaluated targetedUVB (7–19), 4 evaluated topical PUVA (20–23), 3 com-pared topical PUVA vs. targeted UVB (24–26), and 3evaluated PDT (27–29). Six of the included studies wererandomized controlled trials (RCTs) and 17 were caseseries. Of the six RCTs, only three compared the efficacy oftargeted UVB phototherapy vs. topical PUVA (24–26).From these three studies, we directly compared the efficacyof topical PUVA vs. targeted UVB phototherapy. We thenobtained the overall efficacy estimates of each type of thetargeted phototherapy treatments by pooling the patientoutcomes from the 23 included studies. In both of theseassessments, our primary outcome of interest was a 75%reduction in severity score from baseline. Some of thestudies have two groups that the authors used to compare

two different treatment protocols; we refer to these groupsin the figures as groups A and B.

Topical PUVA vs. targeted UVB phototherapy

Three RCTs compared the efficacy of topical PUVA withtargeted UVB phototherapy (24–26). Two of them usedlocalized NB-UVB (311–313-nm) light (24, 26) and oneused excimer (308-nm) light as the source of targeted UVBphototherapy (25); none of them used excimer (308-nm)laser. Neumann et al. found no difference between excimer(308-nm) light and topical PUVA (25), whereasAsawanonda et al. and Sezer et al. studies showed topicalPUVA to be more effective than localized NB-UVB (311–313-nm) light (24, 26). A meta-analysis using both thefixed effects and the random effects model of the abovestudies to compare topical PUVA vs. targeted UVBphototherapy favored topical PUVA (Fig. 2). Fixed effectsmodels showed significantly better patient outcome usingPUVA compared with targeted UVB. However, CochraneQ statistics (6.244, df = 2) showed significant heterogene-ity between studies (P = 0.044) and I2 was almost closer to70%. Therefore, our conclusion was based on the randomeffects model, which indicated that PUVA had a statisti-cally nonsignificant (P = 0.183) advantage over targetedUVB. The pooled OR based on the random effects modelwas 3.48 [95% confidence interval (CI) 0.56–22.84].

Targeted UVB phototherapy

There were 15 studies meeting the inclusion criteria thatevaluated excimer (308-nm) laser, excimer (308-nm) light,and NB-UVB (311–313-nm) light for the treatment of

Studies excluded (n = 719)- Review (n = 197)

- Studies not involvingtargeted phototherapy andrepeated studies (n = 522)

Studies identified by literature search(n = 765)

Studies reviewed for more details(n = 46)

Included studies (n = 23)- Studies evaluating targeted UVB (n = 13)- Studies evaluating topical PUVA (n = 4)

- Studies comparing targeted UVB vs.topical PUVA (n = 3)

- Studies evaluating PDT (n = 3)

Studies excluded (n = 23)- Studies not including the

primary outcome (n = 19)- Studies with less than 10

patients (n = 3)- Studies not having clear

treatment protocol (n = 1)

Fig. 1. Flow chart. UVB, ultraviolet B; PUVA, psoralen plusultraviolet A; PDT, photodynamic therapy.

Efficacy of localized phototherapy for psoriasis


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plaque psoriasis (7–19, 24, 26). The pooled weighted esti-mate of the percentage of patients achieving 75% reduc-tion in their severity score from these studies was 61%(95% CI 50–71%) (Fig. 3). The main side effects, which arepainful erythema and blistering, ranged from 0% to 92%.This large difference was attributable to the different treat-ment protocols used in these studies. The pooled weightedestimate for painful erythema and blistering was 16%(95% CI 4–31%).

By comparing the pooled weighted estimate, the efficacywas higher in studies with higher treatment frequency, twoto three treatments per week (66%) than studies withlower treatment frequency, once every 7–14 days (54%)(Fig. 4). The starting dose for targeted UVB studies waseither based on minimal erythema dose (MED), or using afixed dose or skin phototype. There were no large differ-ences between the efficacies in studies using MED as start-ing dose (63%) (95% CI 50–75%) vs. studies using startingdoses based on skin phototype/fixed dose (57%) (95% CI

37–77%) (Fig. 5). The efficacy of different forms of tar-geted UVB was as follows: 70% for excimer (308-nm) laser,59% for excimer (308-nm) light, and 49% for localizedNB-UVB (311–313-nm) light (Fig. 6).

Topical PUVA

Six studies evaluating topical PUVA met the inclusion cri-teria (20–24, 26). The pooled weighted estimate of theefficacy from these studies was 77% (95% CI 62–89%)(Fig. 7). The percentage of patients who developed painfulerythema or blisters ranged from 0% to 27% with anaverage of 5%.

By comparison of the pooled effect estimate, studies withthree to four treatments per week showed higher efficacythan studies with one to two treatments per week (87% vs.50%) (Fig. 8). The starting dose was either based onminimal phototoxic dose (MPD) or a fixed dose. Similar totargeted UVB studies, there were no obvious differences in

Study name Statistics for each study MH odds ratio and 95% CI

MH odds Lower Upper ratio limit limit Z Value P Value

Sezer 2007

Neumann 2006

0.00125.186 3.529 179.728 3.218Aswanonda 2007 9.648 0.780 0.4351.907 0.377

1.041 0.178 6.076 0.045 0.9643.484 0.556 21.840 1.333 0.183

0.01 0.1 1 10 100

Favours A Favours B

Meta Analysis

Meta Analysis

Fig. 2. Comparison of the efficacyof topical psoralen plus ultravioletA vs. non-laser targeted ultravioletB phototherapy in psoriasis. (A:targeted ultraviolet B; B: topicalpsoralen plus ultraviolet A). CI,confidence interval.

StudyNistico 2006Nistico 2009

Mavilia 2005 AMavilia 2005 BLapidoth 2007

Aswanonda 2008Kaur 2006

Amompinyokeit 2006 ASezer 2007

Feldman 2002Gattu 2009

Taibjee 2005Gerber 2003 AGerber 2003 B

Bonis 1997Goldinger 2006

Trehan 2002

OverallQ = 132.91, P = 0.00, I2 = 88%

Prev (95% Cl)0.796 (0.677, 0.894)0.566 (0.486, 0.644)0.667 (0.550, 0.774)0.319 (0.214, 0.434)0.643 (0.455, 0.812)0.417 (0.150, 0.709)0.600 (0.277, 0.885)0.333 (0.091, 0.628)0.400 (0.215, 0.600)0.839 (0.768, 0.899)0.538 (0.261, 0.804)0.409 (0.211, 0.623)0.850 (0.780, 0.909)0.814 (0.682, 0.918)1.000 (0.834, 1.000)0.313 (0.105, 0.564)0.550 (0.327, 0.764)

0.612 (0.505, 0.714)

6.5707.0286.7176.7176.0134.9004.6104.9005.8906.9675.0235.7426.9576.4064.6105.3265.624

100.000

% Weight

0.2 0.4 0.6 0.8 1

Fig. 3. The efficacy of targetedultraviolet B phototherapy inpsoriasis. CI, confidence interval.

Almutawa et al.


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the efficacy of topical PUVA between studies using MPD asa guide for the starting dose (71%) vs. studies using a fixedstarting dose (79%) (Fig. 9).

Danno et al. investigated the incubation period oftopical psoralen and found no difference in the efficacybetween 5-min and 2-h incubation periods. However, the2-h group had a higher percentage of painful erythema andblistering (27%) compared with the 5-min group (0%).The incubation periods of the other studies were between15–30 min.

PDT

Three studies that investigated aminolevulinic acid (ALA)-PDT met the inclusion criteria (27–29). The pooled effi-cacy estimate from these studies was 22% (95% CI10–37%) (Fig. 10). The main side effect was pain thatoccurred in 80–100% of the patients, and in 30–38% ofthem, it was described as intolerable. From these studies,

groups treated with high doses (10–30 J/cm2) (27, 28)achieved higher efficacy (33–50%) as compared withgroups treated with low doses (5–10 J/cm2) (10–21%)(28, 29).

DISCUSSION

The aim of this systematic review was to determine theefficacy and the short-term safety of targeted UVBphototherapy, topical PUVA, and PDT in the treatmentof localized plaque psoriasis, including palmoplantarpsoriasis.

Topical PUVA was three times more effective than non-laser targeted UVB phototherapy, as shown by our meta-analysis of three studies comparing these two treatments.However, this was not statistically significant (Fig. 2) (24–26). An average of 61% of patients who were treated bytargeted UVB phototherapy achieved more than 75%reduction in their severity score (Fig. 3). Subgroup analysis

Study

Study

(a)

(b)

Lapidoth 2007

Nistico 2006

Nistico 2009

Mavilia 2005 A

Mavilia 2005 B

Aswanonda 2008

Amornpinyokeit 2006 A

Kaur 2006

Sezer 2007

Feldman 2002

Gattu 2009

Taibjee 2005

Gerber 2003 A

Gerber 2003 B

Bonis 1997

Goldinger 2006

Trehan 2002

Overall

Overall

Q = 65.82, P = 0.00, I2 = 85%

Q = 36.57, P = 0.00, I2 = 86%

Prev (95% Cl)pooled estimate

pooled estimate

0.64 (0.45, 0.81) 9.53

0.80 (0.68, 0.89) 18.09

0.57 (0.49, 0.64) 19.84

0.67 (0.55, 0.77) 18.65

0.32 (0.21, 0.43) 18.65

0.42 (0.15, 0.71) 12.39

0.33 (0.09, 0.63) 12.39

0.54 (0.38, 0.69) 100.00

0.60 (0.28, 0.89) 7.25

0.40 (0.21, 0.60) 9.33

0.66 (0.53, 0.78) 100.00

0.84 (0.77, 0.90) 11.09

0.54 (0.26, 0.80) 7.92

0.41 (0.21, 0.62) 9.08

0.85 (0.78, 0.91) 11.08

0.81 (0.68, 0.92) 10.17

1.00 (0.83, 1.00) 7.25

0.31 (0.11, 0.56) 8.41

0.55 (0.33, 0.76) 8.89

% Weight

Prev (95% Cl) % Weight

0.2 0.4 0.6 0.8 1

0.2 0.4 0.6 0.8

Fig. 4. The efficacy of targetedultraviolet B phototherapyaccording to the frequency oftreatments: (a) 2–3/week vs. (b)every 7–14 days. CI, confidenceinterval.



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of the three modalities of targeted UVB phototherapyshowed excimer (308-nm) laser to be more effective (70%)than excimer (308-nm) light (59%) and NB-UVB (311–313-nm) light (49%) (Fig. 6). An average of 16% of thetreated patients developed painful erythema or blisters.With regard to topical PUVA, 77% of the patients achieved75% reduction in their severity score (Fig. 7).

Different variables in the treatment protocols wereevaluated in our analysis to find the most effective proto-col. When starting doses of the targeted UVB studies werecompared, no noticeable differences were noted in the effi-cacy between studies using MED vs. studies using fixeddose or skin phototype (Fig. 5). Through comparison oftwo to three treatments per week vs. one treatment every7–14 days, we found that the higher frequency treatmentswere more effective (Fig. 4).

A similar evaluation of topical PUVA studies was per-formed, yielding similar results. There were no noticeable

differences in the efficacies of studies using MPD vs.studies using fixed doses (Fig. 9). Furthermore, studieswith higher frequencies (three to four treatments perweek) were more effective than studies with lower frequen-cies (one to two treatments per week) (Fig. 8). However,this conclusion should be interpreted with caution, as thestudies analyzed had variable increment regimens as wellas different total numbers of treatments. Both of thesevariables, which we were unable to control, could have hadan effect on overall efficacy.

A recent systematic review evaluating the efficacy of totalbody PUVA vs. NB-UVB in psoriasis found that startingdoses had no effect on the efficacy of treatments (30). Thiswas consistent with our data involving targeted UVBtherapy. In contrast to our analysis, the review found thatthe frequency of treatments had no effect on efficacy (30).However, when the treatment frequencies of totalbody NB-UVB individual studies were analyzed (while

Study

Study

Nistico 2006

Nistico 2009

Sezer 2007

Gattu 2009

Bonis 1997

Goldinger 2006

(a)

(b)

Lapidoth 2007

Mavilia 2005 A

Mavilia 2005 B

Aswanonda 2008


Kaur 2006

Feldman 2002

Taibjee 2005

Gerber 2003 A

Gerber 2003 B

Trehan 2002

Overall

Overall

Q = 97.27, P = 0.00, I2 = 89%

Q = 20.10, P = 0.00, I2 = 80%

pooled estimate

pooled estimate

0.80 (0.68, 0.89) 9.09

0.67 (0.55, 0.77) 9.28

0.33 (0.09, 0.63) 6.84

0.32 (0.21, 0.43) 9.28

0.64 (0.45, 0.81) 8.34

0.42 (0.15, 0.71) 6.84

0.60 (0.28, 0.89) 6.45

0.84 (0.77, 0.90) 9.62

0.41 (0.21, 0.62) 7.98

0.85 (0.78, 0.91) 9.60

0.81 (0.68, 0.92) 8.87

0.55 (0.33, 0.76) 7.82

0.63 (0.50, 0.75) 100.00

0.57 (0.37, 0.77) 100.00

0.57 (0.49, 0.64) 25.55

0.40 (0.21, 0.60) 21.17

0.54 (0.26, 0.80) 17.89

0.31 (0.11, 0.56) 19.03

1.00 (0.83, 1.00) 16.36



0.2 0.4 0.6 0.8 1

0.2 0.4 0.6 0.8

Fig. 5. The efficacy of targetedultraviolet B phototherapyaccording to the starting dose:(a) minimal erythema dose vs. (b)non- minimal erythema dose(fixed dose or skin phototype).CI, confidence interval.

Almutawa et al.


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controlling other variables), it was found that the threetreatments per week were more effective than the two treat-ments per week. Five treatments per week achieved slightlyfaster remissions when compared with three treatments perweek. However, higher frequency treatment was associatedwith an increased incidence of side effects (31, 32).

Overall, PDT in our review showed low efficacy and ahigh percentage of pain (that was intolerable in one thirdof the patients). This result was supported by the British

Association of Dermatologists guidelines, which did notsupport the use of ALA-PDT in the treatment of psoriasis(33). The included PDT studies examined various ALAconcentrations, radiation doses, and light sources in anattempt to increase the efficacy and reduce pain. It is pos-sible that photosensitizers other than ALA might play arole in the treatment of psoriasis in the future. Forexample, a study by Salah et al. used methylene blue(0.1%) with light-emitting diode light (570 nm,

Study

Study

Nistico 2006

Nistico 2009

Gattu 2009

Bonis 1997

Goldinger 2006

(a)

(b)

(c)

Mavilia 2005 A

Mavilia 2005 B

Feldman 2002

Taibjee 2005

Gerber 2003 A

Gerber 2003 B

Trehan 2002

Overall

Q = 48.22, P = 0.00, I2 = 85%

Study

Overall

Q = 32.98, P = 0.00, I2 = 91%

Overall

Q = 5.06, P = 0.28, I2 = 21%

pooled estimate

pooled estimate

pooled estimate

0.84 (0.77, 0.90) 15.17

0.80 (0.68, 0.89) 24.11

0.57 (0.49, 0.64) 26.29

0.67 (0.55, 0.77) 24.80

0.32 (0.21, 0.43) 24.80

0.54 (0.26, 0.80) 10.62

0.41 (0.21, 0.62) 12.27

0.85 (0.78, 0.91) 15.14

0.81 (0.68, 0.92) 13.82

1.00 (0.83, 1.00) 9.69

0.31 (0.11, 0.56) 11.31

0.55 (0.33, 0.76) 11.99

0.70 (0.55, 0.83) 100.00

0.59 (0.40, 0.77) 100.00

0.49 (0.37, 0.61) 100.00

0.40 (0.21, 0.60) 26.87

0.33 (0.09, 0.63) 15.40

0.60 (0.28, 0.89) 13.28

0.42 (0.15, 0.71) 15.40

0.64 (0.45, 0.81) 29.06




0.2 0.4 0.6 0.8 1

0.2 0.4 0.6 0.8

0.2 0.4 0.6 0.8

Lapidoth 2007

Sezer 2007

Aswanonda 2008


Kaur 2006

Fig. 6. The efficacy of (a) excimerlaser, (b) excimer light, and (c)targeted narrowband-ultraviolet Blight in psoriasis. CI, confidenceinterval.



7

565 mW/cm2, 5 J/cm2) resulted in 68% of the patientsachieving ≥ 75% reduction in their severity score after amean of nine treatments (34).

There were limitations to our analyses. Despite theincreasing use of targeted phototherapy for psoriasis,there were a limited number of randomized controlledstudies that assessed efficacy and safety. Moreover, this

handful of studies recruited only a small number ofpatients with the largest trial including only 163 patients(11). The heterogeneity of the treatment protocols inregard to the starting dose, increment, treatment fre-quency, and the use of different severity scores to assessefficacy was another limitation. It should also be clearthat the end points in the included studies did not use the

Study

Overall

Q = 18.17, P = 0.01, I2 = 61%

pooled estimate

1.00 (0.83, 1.00) 11.84

0.57 (0.19, 0.92) 10.09

0.43 (0.08, 0.81) 10.09

0.80 (0.49, 0.99) 11.84

0.87 (0.64, 1.00) 13.76

0.80 (0.55, 0.97) 13.76

0.92 (0.77, 1.00) 15.89

0.50 (0.22, 0.78) 12.72

0.77 (0.62, 0.89) 100.00

1


Sezer 2007

Danno 1983 B

Danno 1983 A

Behrens 1999

De Rie 1995 A

Grundmann-Kollmann 2004

De Rie 1995 B

Aswanonda 2008

Fig. 7. The efficacy of topicalpsoralen plus ultraviolet A inpsoriasis. CI, confidence interval.

(a)

(b)

pooled estimate

pooled estimate

1.00 (0.83, 1.00) 13.55

0.80 (0.49, 0.99) 13.55

0.87 (0.64, 1.00) 20.00

0.80 (0.55, 0.97) 20.00

0.92 (0.77, 1.00) 32.90

0.87 (0.79, 0.94) 100.00

0.50 (0.22, 0.78) 45.45

0.43 (0.08, 0.81) 27.27

0.57 (0.19, 0.92) 27.27

0.50 (0.31, 0.69) 100.00



0.2 0.4 0.6 0.8

0.6 0.8 1

Aswanonda 2008

De Rie 1995 B

De Rie 1995 A

Study

Study

Overall

Q = 3.86, P = 0.43, I2 = 0%

Overall

Q = 0.24, P = 0.89, I2 = 0%

Sezer 2007

Danno 1983 B

Danno 1983 A

Behrens 1999


Fig. 8. The efficacy of topicalpsoralen plus ultraviolet Aaccording to the frequency oftreatments: (a) 3–4/week vs. (b)1–2/week. CI, confidence interval.

Almutawa et al.


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scoring system such as psoriasis area severity index andpsoriasis severity index in the same manner that it is usedin the evaluation of systemic therapy.

We suggest that future studies on localized photo-therapy should use a randomized controlled designwith appropriate blinding; an appropriate and con-sistent scoring system should be developed and used toassess therapeutic response on these localized areas.

Studies should also use clearly described protocols inregard to starting doses, increments, frequencies, totalcumulative doses, and total number of treatments toreach the end points. Studies comparing different treat-ment protocols such as starting dose, treatment fre-quency, and increment regimen would help to developthe optimal protocol with the highest possible efficacyand safety.

pooled estimate

pooled estimate

1.00 (0.83, 1.00) 34.76

0.80 (0.49, 0.99) 16.23

0.87 (0.64, 1.00) 20.22

0.80 (0.55, 0.97) 20.22

0.92 (0.77, 1.00) 25.34

0.50 (0.22, 0.78) 17.99

0.71 (0.25, 1.00) 100.00

0.79 (0.65, 0.91) 100.00

0.57 (0.19, 0.92) 32.62

0.43 (0.08, 0.81) 32.62



0.2 0.4 1

1

0.6 0.8

Study(a)

(b)Study

Overall

Overall

Q = 10.12, P = 0.01, I2 = 80%

Q = 7.75, P = 0.10, I2 = 48%

Sezer 2007

Danno 1983 B

Danno 1983 A

Behrens 1999

De Rie 1995 A


De Rie 1995 B

Aswanonda 2008

Fig. 9. The efficacy of topicalpsoralen plus ultraviolet Aaccording to the starting dose: (a)minimal pigment dose vs. (b) fixeddose. CI, confidence interval.

pooled estimate

0.50 (0.22, 0.78) 16.45

0.20 (0.01, 0.51) 15.06

0.14 (0.03, 0.29) 22.83

0.07 (0.00, 0.20) 22.83

0.31 (0.15, 0.49) 22.83

0.22 (0.10, 0.37) 100.00


0.20 0.4 0.6 0.8

Study

Fransson 2005

Radakovic-Fijan A 2005

Radakovic-Fijan B 2005

Radakovic-Fijan C 2005

Robinson 1999

Overall

Q = 11.30, P = 0.02, I2 = 65% Fig. 10. The efficacy ofphotodynamic therapy in psoriasis.CI, confidence interval.



9

CONCLUSIONS

Despite the limitations of this systematic review, it can beconcluded that topical PUVA and targeted UVBphototherapy are very effective in the treatment of local-ized psoriasis. Both should be considered if topical treat-ments fail prior to progressing to systemic treatments or

biologics. Topical PUVA therapy appears to be moreeffective than non-laser targeted UVB phototherapy.However, some studies showed that the efficacy ofexcimer (308-nm) laser approximates that of topicalPUVA. PDT with ALA showed low efficacy and highincidence of side effects when used to treat localizedpsoriasis.

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Efficacy of localized phototherapy and photodynamic therapy for psoriasis: a systematic review and meta-analysis