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Narrowband UV-B Phototherapy vs Photochemotherapy in the Treatment of Chronic Plaque-Type Psoriasis

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To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. Open, nonrandomized, intraindividually controlled paired comparison study. Phototherapeutic unit in a university hospital. Twenty-five patients with chronic plaque-type psoriasis. Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.
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Narrowband UV-B Phototherapy vs
Photochemotherapy in the Treatment
of Chronic Plaque-Type Psoriasis
A Paired Comparison Study
Adrian Tanew, MD; Sonja Radakovic-Fijan, MD; Michael Schemper, PhD; Herbert Ho¨nigsmann, MD
Objective: To compare the therapeutic efficacy of nar-
rowband (TL-01) UV-B phototherapy vs photochemo-
therapy (psoralen–UV-A [PUVA]) in patients with chronic
plaque-type psoriasis.
Design: Open, nonrandomized, intraindividually con-
trolled paired comparison study.
Setting: Phototherapeutic unit in a university hospital.
Patients: Twenty-five patients with chronic plaque-
type psoriasis.
Interventions: Paired irradiations with threshold ery-
themogenic doses of narrowband UV-B and PUVA were
given to the patients’ dorsal aspect including the arms
and legs. Treatment was performed 3 times weekly until
complete or almost complete clearing with one or both
regimens or over a maximum period of 18 exposures.
Main Outcome Measures: Assessment of the Psoriasis
Area and Severity Index (PASI) in each half of the patient’s
dorsal aspect before and after treatment with the 2 regimens.
Results: The median pretreatment PASI score of 16
(range, 6.2-23.4) was reduced by 84% to 2.5 (range,
0-12.6) by the narrowband UV-B treatment and by 89%
to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical
analysis of these data showed a tendency for PUVA
being superior to narrowband UV-B although the differ-
ence remained below the level of significance (P= .17).
However, a clear effect of the pretreatment PASI score
on the therapeutic outcome was found. Patients with
higher baseline PASI scores responded significantly bet-
ter to PUVA than to narrowband UV-B (P= .03).
Conclusions: Our data demonstrate that in many pa-
tients with plaque-type psoriasis, narrowband UV-B is
comparably as effective as PUVA and, given the lack of
photosensitizer-related adverse reactions and the possi-
bly lower long-term cancer risk, can be considered as first-
line treatment. Treatment with PUVA, on the other hand,
remains the mainstay for patients with high PASI scores
who do not respond or whose psoriasis cannot be con-
trolled adequately by narrowband UV-B.
Arch Dermatol. 1999;135:519-524
therapy with broadband
UV-B and photochemo-
therapy (psoralen–UV-A
[PUVA]) are very effi-
cient and widely used treatment modali-
ties for psoriasis. The choice of treatment
depends on the type and severity of pso-
riasis, the patient’s age and general health,
and the consideration of treatment-
associated long-term risks. Comparative
studies have shown that PUVA is thera-
peutically more effective than broadband
UV-B radiation.1-4 Conversely, treatment
with UV-B is much easier to perform, re-
quires less precautions to prevent acute ad-
verse reactions, and seems to harbor a con-
siderably lower carcinogenic potential than
PUVA.5-7 Based on these differences, broad-
band UV-B phototherapy is primarily in-
dicated in patients with mild to moderate
psoriasis, whereas for severe forms of
PUVA is indicated.
This rough distinction between the
use of phototherapy and PUVA for pso-
riasis had to be reevaluated when in the
early 1980s a fluorescent lamp emitting
narrowband UV-B between 311 and 313
nm (referred to as the TL-01 lamp) was
developed by Philips to improve the effi-
cacy of phototherapy.8,9 The rationale for
manufacturing such a lamp was derived
from action spectra studies for the pho-
totherapy of psoriasis in which longer
wavelengths in the UV-B region were in-
dicated to have the best ratio of antipso-
For editorial comment
see page 589
From the Divison of Special and
Environmental Dermatology,
Department of Dermatology
(Drs Tanew, Radakovic-Fijan,
and Ho¨ nigsmann), Section of
Clinical Biometrics,
Department of Medical
Computer Sciences
(Dr Schemper), University of
Vienna Medical School, Vienna,
©1999 American Medical Association. All rights reserved.
by KennethOif, on February 14, 2008 www.archdermatol.comDownloaded from
riatic to erythemogenic activity.10,11 Several authors sub-
sequently investigated the therapeutic effectiveness of
narrowband UV-B by either comparing the treatment re-
sults for the new lamp with those from previous trials
using broadband UV-B12 or by means of bilateral com-
parison studies.13-19 These investigations confirmed the
efficacy of narrowband UV-B treatment and showed that
it provides for faster clearing, less burning reactions, and
longer periods of remission12 than conventional broad-
band UV-B phototherapy. The relative efficacy of nar-
rowband UV-B in comparison to PUVA was investi-
gated by van Weelden et al20 in a pilot study of 10 patients
with widespread psoriasis vulgaris.On average the same
results were found with both treatments. Green et al21
treated 3 groups of 15 patients each with either narrow-
band UV-B or etretinate plus narrowband UV-B or etreti-
Twenty-five patients with skin type II or III who con-
sented to participate after having received full informa-
tion on the setup and the purpose of the trial were con-
secutively enrolled in this open paired-comparison study.
All of these patients had generalized, chronic plaque-type
psoriasis in a largely symmetrical distribution and had not
received any specific antipsoriatic treatment within the last
4 weeks prior to the study. At the beginning and at the end
of the study the Psorias Area and Severity Index (PASI)
score22 was determined separately for each half of the pa-
tient’s dorsal aspect (hereafter, half-side).
The PUVA treatment was performed with a liquid prepa-
ration of 8-methoxypsoralen (methoxsalen) (Oxsoralen;
Gerot Pharmazeutika, Vienna, Austria) at a dosage of 0.6
mg/kg. Prior to the initiation of the half-side comparison
first the minimal erythema dose of narrowband UV-B
(MEDTL-01) and subsequently the minimal phototoxic dose
(MPD)23 were determined in each patient. Treatment was
given 3 times weekly on Monday, Wednesday, and Friday
in an irradiation unit for supine therapy. No additional spe-
cific systemic or local antipsoriatic therapy was given; how-
ever, the patients were allowed to apply emollients after
the treatments.
To reduce the patient’s additional expenditure on time,
the half-side comparison was performed only on the dor-
sal side of the whole body that included the dorsal aspect
of the arms and legs. On each treatment day the patient first
received the narrowband UV-B irradiation on the right side
of the dorsal aspect. During the irradiation the rest of the
body was covered by 4 layers of white, tightly woven cot-
ton that completely prevented the transmission of UV light.
Immediately after the UV-B exposure, the patients in-
gested the psoralen capsules. One hour later, the left side
of the patient’s dorsal aspect and subsequently the whole
ventral aspect were exposed to UV-A, while the body area
previously treated with narrowband UV-B was shielded from
receiving additional UV-A radiation. The initial irradia-
tion dose was 1 MEDTL-01 and 1 MPD. Patients with a nega-
tive MPD test were treated with a skin type–based initial
UV-A dose of 1 J/cm2for skin type II and 2 J/cm2for skin
type III. Subsequent dose adjustments were based on the
patient’s history and the clinical examination and aimed
at eliciting or maintaining a slight erythematous reaction
with both treatments. The irradiation dose was unaltered
when the patients reported or still had erythema and was
increased by 20% in skin type III and by 10% in skin type
II patients, respectively, in the absence of an erythema-
tous response. Owing to the different time courses of
erythema formation, the narrowband UV-B dose was in-
creased, when required, at each visit, whereas the PUVA
dose was adjusted not earlier than 72 hours after the last
The half-side treatment was performed until com-
plete or almost complete (minimally infiltrated, nonscal-
ing residual plaques) clearing occurred in the narrow-
band UV-B– and/or PUVA-treated skin areas or over a
maximum period of 18 exposures. Patients who at the end
of the study had not achieved complete or almost com-
plete clearing with one or both treatments were either con-
tinued on the more effective regimen, or, when both treat-
ments had given an equal result, on the subjectively preferred
regimen until complete clearing occurred. No mainte-
nance treatment was added.
Phototesting and treatment with narrowband UV-B was done
with a Waldmann UV 3003 lay down irradiation unit (Wald-
mann; Werk fu¨ r Lichttechnik, Schwenningen, Germany)
equipped with 15 Philips TL 100W / 01 fluorescent tubes.
The MEDTL-01 was determined by exposing the patient’s but-
tocks to a geometrical dose range between 141 and 566 mJ/
cm2. The irradiance at skin level was, on average, 3.85 mW/
cm2and measured with an IL 1700 research radiometer
(International Light, Newburyport, Mass) and NS 313–
filtered SD 240 probe with a spectral response from 308 to
318 nm (half-power points) and a peak sensitivity at 313
Subsequent to the the MEDTL-01 testing, the MPD was
assessed with a Waldmann PUVA 500 irradiation unit
equipped with 10 Philips TLK 40W / 09N UV-A lamps. The
irradiance at skin level was 10.5 mW/cm2as measured with
a Waldmann UV meter whose spectral sensitivity corre-
sponds to the spectral emission of the UV-A lamps. The
UV-A dose range was 0.5 to 5 J/cm2for skin types I or II
and 1.5 to 9 J/cm2for skin types III or IV.
A Waldmann PUVA 4000 lay down unit equipped
with 40 Sylvania FR 90 T 12 / PUVA fluorescent tubes
was used for the therapeutic irradiations. The irradiance
was on average 12.6 mW/cm2as measured by an inte-
grated radiometer.
Within the framework of a hierarchical model an analysis
of covariance was performed using the GLM program of
SAS. Thus, the possible effect of the baseline PASI score,
the treatment, and the interaction between the baseline PASI
score and treatment were analyzed taking into account the
block structure of the study (each patient receiving both
©1999 American Medical Association. All rights reserved.
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nate plus PUVA. They observed a 100% sucess rate in
the etretinate-PUVA group as opposed to a 93% success
rate in the etretinate-narrowband UV-B group and an 80%
success rate in the narrowband UV-B monotherapy group.
A direct comparison between narrowband UV-B and
PUVA was not included in that study.
The present investigation was undertaken to evalu-
ate on a larger scale the therapeutic potential of narrow-
band UV-B phototherapy in relation to PUVA and to de-
termine whether in patients with moderate to severe
chronic plaque-type psoriasis, narrowband UV-B pho-
totherapy may serve as an effective therapeutic alterna-
tive to PUVA.
All patients completed the study. Of these, 21 patients
consistently had a comparable number of erythemo-
genic events with both treatments during the study
period, whereas in 4 patients the PUVA-induced ery-
thema occurred only after 8 to 13 exposures and on
fewer occasions than with narrowband UV-B. Since it
was the aim of the study to compare the therapeutic
efficacy of equierythemogenic dosages, these latter 4
patients were excluded from evaluation. The remaining
21 patients were of skin types II (7 patients) or III (14
patients), with a median duration of psoriasis of 17
years (range, 1-46 years). In all these patients, the
MEDTL-01 was within the range of test doses with a
median of 400 mJ/cm2(range, 141-566 mJ/cm2). The
MPD test gave a negative result in 3 of the 21 patients.
The median MPD of the remaining 18 patients was 1.5
J/cm2(range, 0.5-5 J/cm2).
The treatment results summarized in Figure 1
show the PASI score of each patient at baseline and
after treatment with PUVA and narrowband UV-B,
respectively. The overall response to PUVA was slightly
superior to narrowband UV-B phototherapy. After a
median of 15 exposures (range, 6-18 exposures) and 38
days (range, 18-53 days), the median baseline PASI
score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5
(range, 0-12.6) by the narrowband UV-B treatment and
by 89% to 1.8 (range, 0-8.2) by the PUVA treatment
(Table). The median cumulative doses of narrowband
UV-B and UV-A were 12.7 J/cm2(range, 1.8-22.3 J/cm2)
and 40.1 J/cm2(range, 6.9-87.5 J/cm2), respectively. By
analysis of covariance, no significant difference was
found in the overall efficacy of the 2 regimens (P= 017).
Psoriasis Area Severity Index Score
Narrowband UV-B
Figure 1.
The Psoriasis Area and Severity Index scores of all patients arranged in order of increasing magnitude before and after treatment with narrowband UV-B
and psoralen–UV-A. There was a significantly better response to psoralen–UV-A than to narrowband UV-B with increasing baseline score (
= .03 by covariance
Treatment Results*
Initial UV
Dose, J/cm2
Final UV
Dose, J/cm2
Total UV
Dose, J/cm2
No. of
Duration, d
PASI† Score
Baseline Final
Narrowband UV-B 0.4 (0.14-0.57) 1.42 (0.48-2.45) 12.7 (1.8-22.3) 15 (6-18) 38 (18-53) 16.0 (6.2-23.4) 2.5 (0-12.6)
Psoralen–UV-A 1.5 (0.5-5.0) 3.1 (0.9-8.6) 40.1 (6.9-87.5) 15 (6-18) 38 (18-53) 16.0 (6.2-23.4) 1.8 (0-8.2)‡
Values are medians (ranges).
PASI indicates Psoriasis Area and Severity Index.
= .17 by analysis of covariance.
©1999 American Medical Association. All rights reserved.
by KennethOif, on February 14, 2008 www.archdermatol.comDownloaded from
However, when the patients were stratified according to
their pretreatment PASI score the correlation to treat-
ment response was significant. With increasing PASI
scores the patients’ psoriasis cleared better with PUVA
than with narrowband UV-B phototherapy (P= .03)
(Figure 1).
In the direct left to right comparison, 4 patients
showed a better response to narrowband UV-B, 6 re-
sponded equally to both treatments (Figure 2), and 11
had a greater degree of clearing with PUVA (Figure 3).
The half-side differences were, however, slight in most
patients. Complete or almost complete clearing was in-
duced on the dorsal half-side by PUVA in 9 patients and
by narrowband UV-B in 7, respectively (2-tailed p = 0.75
by Fisher exact test).
Irrespective of the treatment modality, a higher re-
duction of the PASI score (P,.001) and a higher prob-
ability to clear completely within the study period (P= .03)
was found for patients with lower pretreatment PASI scores.
Only few and minor side effects occurred during the
study period. In the initial phase of treatment, 3 pa-
tients experienced moderate nausea after the ingestion
of the psoralen capsules which, however, did not neces-
sitate any specific antiemetic treatment and subsided spon-
taneously during the later course of treatment. One pa-
tient reported itching in both the narrowband UV-B– and
PUVA-treated skin areas. Another patient developed le-
sional blistering24 on the right side of her back after 14
irradiations with narrowband UV-B.
The development of the TL-01 lamp with a higher
therapeutic potential than conventional broadband
UV-B sources as well as the increasing awareness of
the carcinogenic risk associated with long-term
PUVA6,7 have led to a continuously growing use of
narrowband UV-B phototherapy in psoriasis. With
regard to the relative therapeutic effectiveness of nar-
rowband UV-B and PUVA, however, only sparse data
are available.20,21 Such information is particularly
important for patients with moderate to severe chronic
plaque-type psoriasis as, besides the palmoplantar and
the rare erythrodermic and pustular forms of psoriasis,
it is this type of psoriasis where PUVA is primarily
The only half-side comparison study on narrow-
band UV-B vs PUVA conducted so far was published by
van Weelden et al20 in 1990. They treated 10 patients
with widespread psoriasis vulgaris twice weekly with
slightly erythemogenic dosages over a maximum period
of 4 weeks. Within the relatively short study period “on
average no significant difference was found between the
overall therapeutic effectiveness of narrowband UV-B
and PUVA.” However, the therapeutic result differed
depending on the body site. Whereas the lesions on the
trunk responded better to narrowband UV-B the
oppposite was true for the psoriatic plaques on the arms
Figure 2.
Left, A patient before treatment. Right, The same patient after 14 treatments and a treatment duration of 35 days. Almost complete clearing with
psoralen–UV-A (left side) and narrowband UV-B (right side). The total UV doses were 87.5 J/cm
and 10.6 J/cm
, respectively.
Figure 3.
Left, A patient before treatment. Right, The same patient after 18 treatments and a treatment duration of 44 days. Notable improvement with
psoralen–UV-A (left side) moderate improvement with narrowband UV-B (right side). The total UV doses were 48.5 J/cm
and 16.9 J/cm
, respectively.
©1999 American Medical Association. All rights reserved.
by KennethOif, on February 14, 2008 www.archdermatol.comDownloaded from
and legs. These findings indicated that PUVA might be
more effective for lesions that are more recalcitrant to
In our study treatment was given thrice weekly over
a maximum period of 18 exposures. To apply bioequiva-
lent doses of both irradiations, we followed a slightly ery-
themogenic dosimetry as was done in the trial by van
Weelden et al.20 The overall improvement, ie, the reduc-
tion of the median pretreatment PASI score, did not dif-
fer significantly between the 2 regimens. However, a posi-
tive correlation between the magnitude of the baseline
PASI score and the probability to clear better with PUVA
treatment was found indicating that in patients with high
PASI scores, PUVA is more likely to induce complete or
almost complete remission.
Taken together, our data demonstrate that in many
patients, in particular those with moderate or moderate
to severe psoriasis, narrowband UV-B is comparably as
effective as PUVA whereas in the more severely af-
fected, PUVA is superior. This is in agreement with pre-
vious studies that by retrospective or direct comparison
found a similar efficacy of narrowband UV-B relative to
PUVA in psoriasis19,20 but also revealed that in a subset
of patients treatment with PUVA is required to achieve
a satisfactory response.25
The use of narrowband UV-B offers some major
advantages owing to the fact that it does not depend
on the concomitant administration of a photosensi-
tizer. In oral PUVA psoralen intolerance reactions, the
variability of the psoralen levels, hepatic diseases, and
drug interactions have to be taken into account. In
addition, the systemic photosensitization necessitates
adequate eye protection and prolonged sun avoidance.
With bath PUVA many of these disadvantages are
obviated; however, the requirement of the bathing
procedure limits the broader use of this treatment
Controversial data are found in the literature on the
incidence and severity of burning reactions under nar-
rowband UV-B treatment. Compared with broadband
UV-B, both a lower12,17 as well as a higher fequency26 of
burning episodes or more intense erythematous reac-
tions19 were reported. Differences in the irradiation pro-
tocol and the patient’s skin type seem to be important in
this regard. In our study, none of the patients experi-
enced a severe burning episode with either one of the 2
The consideration of treatment-associated long-
term risks, in particular the carcinogenic potential, is a
central issue in the choice of treatment for patients with
psoriasis. The assessment of cancer risk resulting from
the clinical use of narrowband UV-B is based on retro-
spective studies on broadband UV-B–treated pa-
tients6,7,27,28 and on mouse studies comparing the carci-
nogenicity of broadband vs narrowband UV-B.13,29-31 These
data suggest that the cancer risk of equitherapeutic doses
of narrowband UV-B is not greater than that of broad-
band UV-B and substantially lower than that of PUVA.32,33
This assumption has recently gained further support from
an in vitro study indicating that phototherapy with nar-
rowband UV-B does not produce more DNA damage than
treatment with broadband UV-B.34
Considering the good therapeutic efficacy and the
low profile of acute and possibly also long-term side ef-
fects, we consider narrowband UV-B as first-line treat-
ment for patients with moderate to severe plaque-type
psoriasis. Psoralen–UV-A on the other hand, remains the
mainstay for patients with severe psoriasis whose con-
ditions do not respond or cannot be controlled ad-
equately by narrowband UV-B. The optimum treatment
protocol for narrowband UV-B and, in particular, the av-
erage duration of remission are yet to be determined in
larger patient cohorts.35 In addition, prospective fol-
low-up studies are required to assess the long-term risks
in humans associated with therapeutic exposures to nar-
rowband UV-B radiation.
Accepted for publication November 23, 1998.
Corresponding author: Adrian Tanew, MD, Division
of Special and Environmental Dermatology, Department of
Dermatology, University of Vienna Medical School, Wa¨hr-
inger Gu¨rtel 18 - 20, A - 1090 Vienna, Austria (e-mail:
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... There was no significant difference in the number of days to clear, and NB-UVB phototherapy was as effective as 8-MOP-PUVA. [8] Our study is also in concert with the study by Tanew et al., [9] who corroborated that both treatments were equally effective but opined that oral 8-MOP-PUVA was superior for patients with severe plaque psoriasis, which could not be demonstrated in our study. ...
... In the present study bergapten (5-methoxypsoralen), a structural analog of xanthotoxin was used. Bergapten was isolated from plants belonging to the Apiaceae family and is a well-known photosensitizing agent used in photochemotherapy (Tanew et al., 1999). It also shows anticancer (Panno et al., 2012), antioxidative (Liu et al., 2012), and anti-inflammatory properties (Bose et al., 2011). ...
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Bergapten is a furanocoumarin naturally occurring in the Apiaceae family and it is a well-known photosensitizing agent used in photochemotherapy. In this study, we investigated the influence of bergapten on cognitive function and mechanism underlying these effects in scopolamine-induced memory impairment in male Swiss mice. The passive avoidance test was used to evaluate the efficiency of memory acquisition and consolidation. The results demonstrated that both single and repeated administration of bergapten improved not only the acquisition but also consolidation of memory. The behavioral tests showed that bergapten prevented memory impairment induced by administration of scopolamine. Observed effects may result from the inhibition of acetylcholinesterase activity in the hippocampus and prefrontal cortex. Also, bergapten caused significant anti-oxidative effects. These new findings provide pharmacological and biochemical support for the development of the coumarin’s potential in cognitive deficits.
... [14][15][16] Some studies, however, showed even higher PASI index reduction. 11,17 According to Hönigsmann et al. phototherapy can achieve a PASI score reduction by 75% on average in 75% of patients after 6 weeks. 18 The diversity of published results could be explained with the heterogeneity of the treated patients (sex, age, phototype, clinical variants of psoriasis, pre-treatment disease severity) and the differences in treatment protocol (number and frequency of exposures, dose enhancement). ...
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Introduction: Treatment with ultraviolet light is a well-established and effective treatment option for mild to moderate psoriasis. The aims of the study were to measure the psoriasis area and severity index (PASI) reduction after narrow-band ultraviolet B (NB UVB) therapy, to evaluate the quality of life before and after treatment using the dermatology life quality index (DLQI), and to compare the clinical effectiveness with quality of life improvement. Material and methods: Twenty two patients (13 male and 9 female patients), aged between 21 to 70 years (mean age 40±14.65 years) were enrolled in the study. NB UVB treatment was performed with 10 to 25 (mean 18.5; SD 3.39) procedures with cumulative doses of 5 to 19.4 J/cm2. The baseline median PASI score was 20.027 which decreased after therapy to 11.11. More than PASI 50% reduction was achieved in 40.91% of the patients after at least 6 weeks of treatment and the results are highly statistically significant. Quality of life (QoL) assessed using DLQI was found moderately affected by disease pretreatment. NB UVB therapy significantly increased DLQI score in spectrum of ‘symptoms and feelings’ and ‘treatment’. Discussion: The PASI score reduction that we observed after NB-UVB therapy is consistent with the results reported by other authors. Baseline DLQI scores were indicative of moderate QoL impairments associated with disease. At the same time, the reduction of the DLQI index corresponding to improved QoL correlated with the objective clinical symptom assessment. Conclusion: Our data suggest that DLQI and PASI indexes are important complementary methods for comprehensive health assessment of patients with psoriasis.
... Nowadays, targeted therapy, in particular with antibodies against IL-17 or IL-23, permits complete clinical clearance of skin lesions in a high percentage of cases, at rates similar to those observed after PUVA treatment [31][32][33][34][35] but with an apparently more favorable risk profile. Severity of psoriasis is assessed with tools such as the psoriasis area and severity index (PASI), which scores both involved body area and clinical appearance of psoriatic lesions. ...
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Psoriasis is a chronic inflammatory skin disease that involves numerous types of immune cells and cytokines resulting in an inflammatory feedback loop and hyperproliferation of the epidermis. A more detailed understanding of the underlying pathophysiology has revolutionized anti-psoriatic treatment and led to the development of various new drugs targeting key inflammatory cytokines such as IL-17A and IL-23. Successfully treated psoriatic lesions often resolve completely, leaving nothing visible to the naked eye. However, such lesions tend to recur within months at the exact same body sites. What is left behind at the cellular and molecular levels that potentially reinitiates psoriasis? Here, we elucidate the cellular and molecular “scar” and its imprints left after clinical resolution of psoriasis treated with anti-TNFα, anti-IL-17, or anti-IL-23 antibodies or phototherapy. Hidden cytokine stores and remaining tissue-resident memory T cells (TRMs) might hold the clue for disease recurrence.
Background: In human medicine, narrow-band ultraviolet B (NB-UVB) phototherapy has been used to treat various T-cell-mediated skin diseases. However, the effect of NB-UVB on inflamed canine skin remains uncertain. Objectives: To investigate the effect of NB-UVB phototherapy on the skin of dogs with hapten-induced contact dermatitis. Animals: Seven healthy beagles without skin problems. Methods and materials: Dogs were irradiated with varying doses of NB-UVB to determine the minimal erythema dose (MED). After determining the MEDs of six dogs (excluding one of the seven whose skin did not show a visible reaction), we investigated the effect of NB-UVB on their inflamed skin by topically applying 2,4-dinitrochlorobenzene (DNCB), which causes type 1 helper T cell (Th1)- and cytotoxic T-cell (Tc)1-induced skin inflammation. We then irradiated the skin with NB-UVB. We analysed the treated skin samples via histopathological and immunohistochemical methods, and TdT-mediated dUTP nick-end labelling (TUNEL) to demonstrate apoptotic cells. We also analysed the cytokine gene transcription via real-time quantitative reverse transcription PCR. Results: The NB-UVB MEDs caused mild inflammatory changes yet no severe epidermal exfoliations in the irradiated skin. In DNCB-treated skin irradiated by the NB-UVB MEDs, TUNEL-positive dermal apoptotic cells were increased significantly compared with those of DNCB-treated, nonirradiated skin. INF-γ and TNF-α transcription levels in DNCB-treated, irradiated skin were significantly lower than those in the DNCB-treated, nonirradiated skin. Conclusion and clinical relevance: Phototherapy using NB-UVB MEDs attenuated cutaneous Th1 and Tc1 cytokine responses with minimal skin damage in a canine model of hapten-induced contact dermatitis.
UV-based phototherapy (including psoralen plus UVA (PUVA), UVB and UVA1) has a long, successful history in the management of numerous cutaneous disorders. Photoresponsive diseases are etiologically diverse, but most involve disturbances in local (and occasionally systemic) inflammatory cells or abnormalities in keratinocytes that trigger inflammation. UV-based phototherapy works by regulating the inflammatory component and inducing apoptosis of pathogenic cells. This results in a fascinating and complex network of simultaneous events–immediate transcriptional changes in keratinocytes, immune cells, and pigment cells; the emergence of apoptotic bodies; and the trafficking of antigen-presenting cells in skin—that quickly transform the microenvironment of UV-exposed skin. Molecular elements in this system of UV recognition and response include chromophores, metabolic byproducts, innate immune receptors, neurotransmitters and mediators such as chemokines and cytokines, antimicrobial peptides, and platelet activating factor (PAF) and PAF-like molecules that simultaneously shape the immunomodulatory effects of UV and their interplay with the microbiota of the skin and beyond. Phototherapy's key effects—proapoptotic, immunomodulatory, antipruritic, antifibrotic, propigmentary, and pro-prebiotic—promote clinical improvement in various skin diseases such as psoriasis, atopic dermatitis (AD), graft-versus-host disease (GvHD), vitiligo, scleroderma, and polymorphic light eruption (PLE) as well as cutaneous T-cell lymphoma (CTCL). As understanding of phototherapy improves, new therapies (UV- and non-UV-based) are being developed that will utilize agonists and antagonists as well as antibodies targeting soluble molecules such as cytokines and chemokines, transcription factors, and a variety of membrane-associated receptors.
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• One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light (PUVA). Patients treated with PUVA, in the initial and maintenance period, achieved in general a higher therapeutic score (95% to 100% clearance) than those receiving UV-B therapy. However, taking 80% to 100% improvement as criterion, no difference was found between initial UV-B and PUVA therapy, if less than 50% of the skin surface was affected by psoriasis. If more than 50% of the skin was involved, PUVA was better than UV-B therapy. The maintenance treatment frequency for the UV-B—treated patients for more than a year seemed to be higher than for PUVA-treated patients. A positive correlation was found between response to sunbathing (questionnaire survey) and the response to UV-B phototherapy. An extra UV-B treatment to the leg lesions appeared useless. (Arch Dermatol 1984;120:52-57)
Objective: To compare the therapeutic effectiveness of daily exposure to narrowband (NB) UV-B vs broadband (BB) UV-B with and without tar.Design: Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study. Narrowband UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet. Narrowband UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar (Goeckerman treatment) below the waist.Setting: General clinical research center of a university hospital inpatient unit.Patients: Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study.Main Outcome Measures: Clinical efficacy was measured weekly using psoriasis severity scoring. Therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression).Results: Clinical resolution of psoriasis was achieved on 86% of paired sites treated with NB UV-B vs 73% treated with BB UV-B. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88% of lesions treated with NB UV-B vs 59% treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment. Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment.Conclusions: Narrowband UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis, with faster clearing and more complete disease resolution. The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0— minimum erythema dose exposure. Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases.Arch Dermatol. 1997;133:1514-1522
Forty-five patients with extensive chronic plaque or guttate psoriasis were treated with either narrowband (TL-01) phototherapy, etretinate TL-01 combination therapy (re-TL-01) or etretinate and PUVA (re-PUVA) (15 patients in each group). Re-PUVA was the most effective therapy with 100% satisfactory clearance rate. TL-01 monotherapy had an 80% success rate; the relapse rate compared favourably with re-PUVA (50% in remission after 6 months). In the etretinate-TL-01 group, there was a 93% success rate and a one-third reduction in the total irradiation dose (8.0 J/cm2 vs, 12.7 J/cm2) but the relapse rate was higher, only 33% remaining in remission after 6 months.
Background: Common treatments used for severe psoriasis include psoralen and ultraviolet A radiation (PUVA), methotrexate, ultraviolet B (UVB), and tar. These therapies are often used for prolonged periods and may be carcinogenic. Methods: For more than 13 years, the authors have prospectively determined the incidence of skin cancer and use of treatments for psoriasis in a 1380 patient cohort originally enrolled in a therapeutic trial of PUVA at 16 university centers. Results: Squamous cell carcinoma (SCC) developed in more than one fourth of patients exposed to high doses of PUVA. In this group, the standard morbidity ratio for these tumors was 83 (95% confidence interval [CI], 72-96) compared with the expected number of these tumors in the general population. High-level exposure to methotrexate is a significant independent risk factor for developing SCC (relative risk, 2.1 for high versus low or no exposure; 95% CI, 1.4-2.8). Metastatic disease developed in seven patients with SCC. No significant increase in the risk of SCC was associated with long term exposure to UVB or topical tar, and no substantial increase in the risk of basal cell carcinoma was noted in association with prolonged use of any of these treatments. Conclusions: Long term exposure to PUVA and methotrexate significantly increases the risk of SCC in patients with psoriasis. This risk should be considered in selection of treatment. The ultimate morbidity of these tumors is undetermined.
Fifty two psoriatic patients were treated with a new experimental fluorescent lamp (Philips TL-01) emitting a narrow band at 311 ± 2 nm (UVB) which had the advantage of a reduction in burning and carcinogenic wavelengths when compared with conventional broad band UVB therapy. Results of the ‘311’ treated group when compared with broad band UVB therapy revealed a similar percentage of patients achieving a satisfactory response with fewer burning episodes and an increase in duration of remission.
The therapeutic effectiveness of radiation from a 311 nm ultraviolet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 (P = 0.003), 8.2 vs. 12.0 at week 2 (P = 0.004), and 6.6 vs. 15.6 at week 3 (P = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 (P = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm2 (P = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.
The dramatic effectiveness of this treatment, both in clearing psoriatic lesions and maintaining patients in a state of remission, has been demonstrated in several studies. The rationale of PUVA therapy is to bring psoriasis into remission by repeated, controlled photosensitization reactions which are monitored to remain within a therapeutically desired range. Since phototoxic erythema is a limiting factor, careful attention to dosimetry is essential and it is therefore the dosimetry system which is a key to both the effectiveness and safety of PUVA. This paper outlines and discusses criteria for dosimetry that have proved useful in 230 patients with severe, generalized psoriasis.