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.
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