Ultraviolet A phototherapy for sclerotic skin diseases:
A systematic review
Elisabeth B. M. Kroft, MD, Nadine J. G. Berkhof, MD, Peter C. M. van de Kerkhof, MD, PhD,
Rianne M. J. P. Gerritsen, MD, PhD, and Elke M. G. J. de Jong, MD, PhD
Nijmegen, The Netherlands
Background: Ultraviolet (UV) A-1 phototherapy is now available for a variety of skin diseases.
Increasingly since 1995, there have been investigations of the efficacy of UVA-1 (340-400 nm) therapy
for sclerotic skin diseases. Most studies undertaken treated patients who had localized scleroderma, but
UVA-1 phototherapy is currently also used for other sclerotic skin conditions.
Objective: We sought to assess the efficacy, biological effects, and side effects of UVA-1 in a variety of
sclerotic skin diseases (localized scleroderma, eosinophilic fasciitis, chronic graft-versus-host disease,
lichen sclerosus et atrophicus, scleredema adultorum, necrobiosis lipoidica, POEMS disease, pansclerotic
porphyria cutanea tarda, and drug-induced scleroderma-like disorders).
Methods: The authors searched for publications dated between January 1996 and November 2007 in the
computerized bibliographic database, PubMed. PubMed was searched using medical subject heading terms
and open searches to retrieve the latest reports.
1 on these skin diseases is still growing, and appears promising. Up until now, good results are shown for all
different doses (low, medium, and high) UVA-1 and UVA. There are insufficient data regarding use of high-
medium-, or high-dose UVA-1 therapy. Although UVA-1 has various effects on, for instance, fibroblasts and
inflammatory cells, the precise mode of action remains obscure. The main short-term side effects of UVA-
1 therapy are erythema, pruritus, xerosis cutis, tanning, and recrudescence of herpes simplex infection. More
studies are warranted to investigate the potential long-term risk of photoaging and skin cancer. Currently,
UVA-1 is considered to be less carcinogenic than psoralen plus UVA (PUVA).
Limitations: Because of the limited availability of randomized controlled trials and large cohort studies, it
is difficult to draw firm conclusions on the long-term efficacy, optimum dose, and best treatment regimens
for UVA-1 when administered to patients with sclerosing skin disorders.
Conclusions: Full-spectrum UVA and UVA-1 phototherapy seem effective in the treatment of sclerotic skin
scleroderma and pseudoscleroderma and prevent further disease progression, including contractures.
Further investigations will be needed to determineany additional biological effects of UVA-1. Although long-
term side effects are not yet known, UVA-1 might develop into a promising beneficial and well-tolerated
treatment in the therapeutic armamentarium for sclerotic skin diseases. Long-term studies in large groups
of patients are clearly needed. ( J Am Acad Dermatol 2008;59:1017-30.)
described by Mutzhas et al1in 1981. Longer wave-
lengths in the UVA region have the capacity to reach
the deeper layers of the dermis and possibly the
subcutis. Currently, there are two main UVA-1 sour-
ces, namely fluorescent lamp and metal halide. The
fluorescent lamp cubicles only allow low dose (LD)
(10-30 J/cm2) or moderate/medium dose (MD)
ltraviolet (UV) A-1 is that part of the UV
spectrum that emits photons with a wave-
length of 340 to 400 nm and was first
From the Department of Dermatology, Radboud University
Nijmegen Medical Center.
Funding sources: None.
Conflicts of interest: None declared.
Reprint requests: Elisabeth B. M. Kroft, MD, Radboud University
Nijmegen Medical Center, PO Box 9101, NL-6500 HB Nijmegen,
The Netherlands. E-mail: firstname.lastname@example.org.
Published online October 3, 2008.
ª 2008 by the American Academy of Dermatology, Inc.
GVHD: graft-versus-host disease
LD: low dose
LS: localized scleroderma
MD: medium dose
PUVA: psoralen plus ultraviolet A
TGF: transforming growth factor
(40-70 J/cm2). The high output, high-dose (HD)
metal halide sources allow up to 130 J/cm2.2
Another classification is based on the administered
cumulative dose. HD is then defined as a cumulative
dose of 975 to 1840 J/cm2, MD as a cumulative dose
of 300 to 975 J/cm2, and, finally, LD as a cumulative
dose of 300 J/cm2or lower.
Different types of UVA-1 phototherapy were in-
troduced as innovative and promising therapeutic
options for inflammatory diseases such as atopic
dermatitis.3Since then, it has shown promising
results for a variety of indications.
Encouraged by the clinical success and the diver-
sity of immunomodulatory effects achieved by the
use of UVA-1 therapeutic regimens in a wide variety
of indications, further studies focused on the efficacy
of UVA-1 phototherapy in the treatment of sclerosing
skin diseases. The first report describing the use of
UVA-1 irradiation to treat localized scleroderma (LS)
was published by Kerscher et al4in 1995 and has
since then been followed by case reports and studies
indicating effective treatment of sclerosing skin dis-
eases using UVA-1.
The scleroderma skin disorders comprise a het-
erogeneous group of conditions linked by the pres-
ence of thickened, sclerotic skin lesions. It can
manifest itself as a small indurated plaque to condi-
tions that may cause significant functional and cos-
metic deformity, with a variety of extracutaneous
features.5LS is a primary cutaneous sclerosis.
or deep morphea.6Scleroderma-like disorders, also
called secondary cutaneous sclerosis, are disparate
conditions mimicking cutaneous localized sclerosis,
forexample, chronic graft-versus-host
(GVHD) and drug-induced scleroderma-like disor-
ders such as scleredema of Buschke/adultorum and
Therapeutic options for sclerotic skin diseases
include topical treatments such as topical steroids8or
icillin G,16,17extracorporeal photopheresis,18metho-
trexate,19,20interferon gamma,21antimalarial drugs,22
sulfasalazine,23and psoralen plus UVA (PUVA).24
This review describes the biological effects, side
effects, and therapeutic use of UVA-1 in LS, eosino-
philic fasciitis, and pseudoscleroderma.
Our focus was the use of UVA-1 (340-400 nm)
phototherapy in patients with sclerotic skin diseases.
Moreover, the use of broadband UVA (320-400 nm)
in LS was also evaluated.
The use of PUVA (with 320- to 400-nm UVA) is not
included in this review and neither is systemic
sclerosis or scleroderma (diffuse or limited).
The authors searched for publications dated be-
tween January 1996 and November 2007 in the
computerized bibliographic database PubMed.
Reference lists of these articles were further
retrieved from relevant English, Dutch, or German
original articles, case reports, studies, reviews, let-
ters, or articles in books. The key terms used were:
ultraviolet phototherapy, phototherapy, long wave
therapy, UVA, UV-A, UVA phototherapy, UVA-1,
UVA1, UV-A1, Ultraviolet A1, Ultraviolet A, sclerotic,
sclerosis, sclerosus, sclerodermic,
localized scleroderma, scleroderma, morphea, mor-
phoea, pseudosclerosis,sclerodermalike, secondary
sclerosis, scleredema diabeticorum, scleredema of
Buschke, scleredema adultorum, Graft versus Host,
GVHD, lichen sclerosis, lichen sclerosus, eosino-
philic fasciitis, Shulman
POEMS, medication induced scleroderma, and mu-
cinosis. The PubMed was searched using medical
subject heading terms and open searches to retrieve
the latest reports.
In this review the classification LD, MD, or HD is
1 is defined as a single dose of 10 to 30 J/cm2per
session; MD as a single dose of 40 to 70 J/cm2; and,
finally, HD UVA-1 as a single dose of 70 to 130 J/cm2.
UVA-1 in LS
The classification of LS according to Peterson
et al6is based on 5 general types: plaque morphea,
generalized morphea, bullous morphea, linear mor-
phea, and deep morphea. In addition, eosinophilic
fasciitis can be separately distinguished. Table I
shows, per study, the form of UVA-1, number of
patients, dose, cumulative dose, number of treat-
ments, and evaluation of outcomes.
J AM ACAD DERMATOL
1018 Kroft et al
Table I. UVA-1 phototherapy in localized scleroderma
of outcomes ResultsStudy
MD UVA-1 vs LD UVA-1
C, VAS, H, U Skin status significantly improved in all patients, resulting
in significant reduction in clinical score. MD UVA-1 was
significantly more effective than NB-UVB. No signifi-
cant difference between MD and LD UVA-1. VAS score
for tightness and itching significantly decreased in MD
UVA-1, whereas VAS score for tightness decreased in
LD UVA-1 and NB-UVB. Histologic score (decreased
thickness, decreased elastic fibers, decreased infiltrate)
was only significant for NB-UVB. U revealed that
corium thickness was significantly decreased after MD
After 24 treatments, [80% of lesions were completely
cleared, U and H revealed nearly normal skin thickness.
After 24 sessions [80% of lesions were completely
cleared (clinical improvement). U revealed normal skin
thickness. H revealed structure of dermal collagen
returned to normal human dermis.
Intraindividual control study. In all patients, remarkable
softening of sclerosis. Significant reduction of mean
concentrate of collagen/surface area in exposed
plaques were detected, also thickness of dermis was
reduced. Covered plaques showed no significant
reduction of concentration of collagen/surface area.
All 3 groups showed remarkably softening of lesions. No
significant difference in session number of first seen
improvement or degree of softening. Late, fibrotic
white plaques showed fair to poor responses, whereas
early indurated lesions responded well. Collagen bun-
dles appeared thinner in 10- and 20-J/cm2groups, but
no significant difference could be found among 3
groups in this point.
In 3/5 patients, complete clearance after UVA-1. 2/5
Patients noticed softening of sclerotic plaques. In all
patients, increased expression of collagenase in
fibroblasts after irradiation was found with nearly
normal dermal collagen thickness.
Kreuter et al,25
LD UVA-11020 480 24C, H, U Kerscher et al,4
Kerscher et al,29
LD UVA-120 20600 30 C, H, U
UVA 1220400 20C, H
El-Mofty et al,33
El-Mofty et al,35
LD UVA-15 20 480 24 C, H, ISH, IHC
Gruss et al,28
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VOLUME 59, NUMBER 6
Kroft et al
Table I. Cont’d
C, PCRIn 18/20 patients, remarkable softening of lesions was
observed. Significant decrease in H sections of
collagen I, III, and TGF-b, and increase in collagenase
and IFN-g (significantly higher in group receiving
20 J/cm2). Relative increase was greatest in
collagenase, IFN-g, and TGF-b. No significant
difference between two groups in clinical response.
All 7 patients noticed decrease of induration and 1/7
patients noticed increased mobility of elbow.
Significant increase of CD341cells was found. Atrophic
lesions remained unchanged.
Intraindividual control study. All patients showed
softening of affected areas and improved elasticity of
skin measured by cutometer. After 12 wk, 7 wk after
therapy, improved elasticity did not last and skin was
same as before therapy. FFT technique did not reveal
change in bundle orientation ratio or bundle spacing.
El-Mofty et al,34
MD UVA-17 30900 30C, H
Camacho et al,30
MD UVA-18 4896020 C, E, FFT
De Rie et al,31
HD UVA-1 vs
C, U, PCR
5/10 Patients, intraindividual control. HD UVA-1: all
patients showed softening of lesions, 4/10 patients
showed complete clearance and one patient revealed
joint mobility, skin thickness, and skin elasticity sig-
nificantly improved. These changes could not be
detected in unirradiated control plaques. LD UVA-1:
2/7 patients showed reduction and softening of le-
sions, no patient showed complete clearance. HD UVA-
1 was superior to LD UVA-1 for all factors examined.
LD UVA-1 and calcipotriol ointment. All patients showed
softening and repigmentation of sclerotic lesions, U
showed decreased dermal thickness. UVA-1 therapy
increased collagenase expression about 20-fold. No
control group of UVA-1 only.
Morphea of eyelid lesion softened, eyelid retraction
Stege et al,27
LD UVA-1 19 Children 2080040C, U (Just
Kreuter et al,32
LD UVA-11 20 60030C Steger and
Gruss et al,28
LD UVA-11 20 64032 C, H, U Resolution of lesions, healing of limb ulcer, and
improvement of joint mobility. Overall thickness of
dermis was significantly less than before treatment.
J AM ACAD DERMATOL
1020 Kroft et al
Randomized controlled trials. One open ran-
domized controlled trial was performed by Kreuter
et al25in 2006. A total of 64 patients with LS were
randomly allocated to 3 groups receiving LD/MD
UVA-1 or narrowband (NB) UVB phototherapy. Skin
status (according to the modified skin score of
Zachariae et al26) significantly improved in all 3
groups, although MD UVA-1 seemed to be more
effective than NB-UVB. There were no significant
differences between LD
Furthermore, there was no significant difference
between LD UVA-1 and NB-UVB. The authors
suggested that the study size (LD UVA-1 n = 27, MD
UVA-1 n = 18, NB-UVB n = 19) was too small to imply
significance on this point. The reduction of the
clinical score was accompanied by an improvement
of the visual analog scale score for itching and
tightness, histologic score, and skin thickness mea-
sured by 20-MHz ultrasound. Only MD UVA-
1 showed a significant decrease of the visual analog
scale score for tightness and itching, whereas LD
UVA-1 and NB-UVB only showed a significant de-
crease of tightness of the sclerotic skin.
Open studies. Most studies performed were
open nonrandomized clinical trials. Stege et al27
found that HD UVA-1 therapy was superior to LD
UVA-1 therapy in patients with LS in decreasing
thickness of the sclerotic skin, softening of the
Several other studies showed that using LD UVA-
1 in different treatment regimens was able to pro-
duce a remarkably good clinical response in patients
with LS.4,25,27-29Several open studies showed a
decrease of clinical assessment of induration30,31
and a significant improvement of elasticity after MD
UVA-1 irradiation.31So far, LD, MD, and HD UVA-
1 phototherapy seem to be effective in the treatment
1 and calcipotriol ointment. All patients showed
softening of the sclerosis and ultrasound showed a
decreased dermal thickness. El-Mofty et al33per-
formed an open study in 2000, whereby 12 patients
All patients showed significant softening of the
sclerosis in this intraindividual controlled study.
The covered plaques showed no significant reduc-
tion of the concentrate collagen per surface area,
measured by an image analyzer. Two more studies
performed by El-Mofty et al34,35showed a remark-
able softening of the sclerosis using 320- to 400-nm
UVA in different treatment regimens.
Case reports. Four patients with morphea were
treated with broadband UVA (320- to 400-nm UVA).
In 3 patients, the skin thickness of the sclerotic
lesions improved, whereas in the other patients no
and MD UVA-1.
All patients showed complete clearance, one of whom
had nonactive lesions. Dermal thickness was
Gruss et al,372001
Patient with overlying LSA, complete clearance after
therapy, H changes of sclerosis disappeared.
Softening of skin and repigmentation.
Yildirim et al,39
Dermal thickness decreased from 1.9 to 1.1 mm and skin
became thinner and softer.
Dermal thickness decreased from 1.8 to 1.4 mm.
Dermal thickness decreased from 1.7 to 1.4 mm.
C, Clinical criteria; E, elastometry/cutometry; FFT, fast Fourier transform; H, histopathology; HD, high dose; IFN, interferon; IHC, immunochemistry; ISH, in situ hybridization; LD, low dose; LSA, lichen
sclerosis et atrophicus; MD, medium dose; NB, narrowband; PCR, polymerase chain reaction; TGF, transforming growth factor; U, ultrasound; UV, ultraviolet; VAS, visual analog score.
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