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Over many centuries, treatment with sunlight or "heliotherapy" was used in the treatment of skin diseases. More than 3500 years ago, ancient Egyptian and Indian healers used the ingestion of plant extracts or seeds in addition to sunlight for treating "leucoderma". Modern phototherapy began with Nobel Prize winner Niels Finsen who developed a "chemical rays" lamp with which he treated patients with skin tuberculosis. However, it took several decades until phototherapy was introduced anew into the dermatological armamentarium. It was the development of photochemotherapy (PUVA) in 1974 that marked the beginning of a huge upsurge in photodermatology. The subsequent development of high intensity UV sources with defined spectra facilitated an optimized therapy for psoriasis and led to an expansion of indications for photo(chemo)therapy also in combination with topical and systemic agents. The introduction of extracorporeal photopheresis in 1987 for cutaneous T-cell lymphoma and of topical photodynamic therapy widely expanded the therapeutic possibilities in dermato-oncology.
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Photochemical &
Photobiological Sciences
PERSPECTIVE
Cite this: Photochem. Photobiol. Sci., 2013,
12,16
Received 25th April 2012,
Accepted 24th May 2012
DOI: 10.1039/c2pp25120e
www.rsc.org/pps
History of phototherapy in dermatology
Herbert Hönigsmann
Over many centuries, treatment with sunlight or heliotherapy was used in the treatment of skin
diseases. More than 3500 years ago, ancient Egyptian and Indian healers used the ingestion of plant
extracts or seeds in addition to sunlight for treating leucoderma. Modern phototherapy began with
Nobel Prize winner Niels Finsen who developed a chemical rays lamp with which he treated patients
with skin tuberculosis. However, it took several decades until phototherapy was introduced anew into
the dermatological armamentarium. It was the development of photochemotherapy (PUVA) in 1974 that
marked the beginning of a huge upsurge in photodermatology. The subsequent development of high
intensity UV sources with dened spectra facilitated an optimized therapy for psoriasis and led to an
expansion of indications for photo(chemo)therapy also in combination with topical and systemic agents.
The introduction of extracorporeal photopheresis in 1987 for cutaneous T-cell lymphoma and of topical
photodynamic therapy widely expanded the therapeutic possibilities in dermato-oncology.
Ancient history
Over many centuries, treatment with sunlight or heliotherapy
was used in the treatment of skin diseases. One form, more
than 3500 years ago, consisted of ingestion of a boiled extract
derived from a weed growing in the Nile Delta, Ammi majus
L. followed by exposure to the Egyptian sun for the treatment
of vitiligo (mentioned in the Papyrus Ebers), which was mista-
kenly thought to be leprosy. Independent of the Egyptian
invention, the Atharva-Veda in India reported about healers
who used a treatment consisting of ingestion of seeds of the
Bavachee plant (Psoralea corylifolia) and sunlight for treating
leucoderma. Around 1100 AD the Arab physician Ibn al-Bitar
in his book Mofradat El-Adwiya mentioned a remedy for
vitiligo with oral extracts from Ammi majus and sunlight. These
crude treatments were the very earliest form of what is now
called PUVA photochemotherapy, a treatment for psoriasis,
vitiligo and other diseases and that uses the same chemical,
psoralen, derived from the same plant source, Ammi majus
L. and followed by exposure to specially designed computer-
ized UVA units. Herodotus in 525 BC reporting on heliotherapy
correlated the strength of the human skull to the degree of
sun exposure (Herodotus, The Histories: I noticed that the
skulls of the Persians are so thin that the merest touch with a
pebble will pierce them, but those of the Egyptians on the other
hand [are] so tough that it is hardly possible to break them with a
stone. I was toldthat the reason was that the Egyptians shave
their heads from childhood, so that the bone of the skull is indu-
rated by the sun.) In the Middle Ages followed the dark
period of phototherapy.
1
Modern phototherapy
In the 19th century, observations were made that sunlight may
be beneficial for medical purposes. In 1877 Downes and Blunt
showed that sunlight exerts a bactericidal action and could kill
anthrax bacilli.
2
In 1890 Palm from Edinburgh suggested that
the sun could play a therapeutic role in rickets.
3
However, real modern phototherapy began with Niels
Ryberg Finsen, the father of ultraviolet therapy. In 1896,
Finsen, aware of the bacteria-destroying eects of sunlight,
developed a chemical rays lamp with which he treated a
friend who had lupus vulgaris; within a few months the
lesions were completely resolved
4,5
(Fig. 1). Finsen then
assembled a focusable carbon-arc torch. With this Finsen
Lamp he treated over 800 patients with lupus vulgaris in his
Phototherapy Institute in Copenhagen (Fig. 2). In total, 80%
were cured.
6
At a time when no antibiotics or anti-inflamma-
tory drugs were available, Finsens phototherapy was a major
breakthrough. In 1903, Finsen was awarded the Nobel Prize in
medicine in recognition of treatment of lupus vulgaris, with
concentrated light rays. So far, the only Nobel Prize ever
awarded for dermatology or photomedicine.
7
Unfortunately,
he was too ill to travel to Stockholm to receive this Prize.
Treatment of lupus vulgaris was not the only example of the
use of phototherapy in dermatology. In 1923, William Henry
Goeckerman introduced his regime (artificial broadband UVB
This article is published as part of a themed issue on current topics in
photodermatology.
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Tel: +43-1-40400-7702; Fax: +43-1-40400-7699;
E-mail: herbert.hoenigsmann@meduniwien.ac.at
16 | Photochem. Photobiol. Sci., 2013, 12,1621 This journal is © The Royal Society of Chemistry and Owner Societies 2013
from a high pressure mercury lamp plus topical coal tar) for
psoriasis. In 1925 he published his first results
8
(Fig. 3). This
treatment became very popular, particularly in the U.S.A, and
was used for decades to treat psoriasis. In 1953, John Ingram,
in the United Kingdom, combined this treatment with anthra-
lin.
9
Surprisingly, Goeckermans or Ingrams regimens have
never been popular in central Europe.
Subsequently, it was found that broadband UVB on its own,
given in slightly erythematous doses, could clear mild forms of
psoriasis, mainly seborrheic and guttate psoriasis (see below).
By the beginning of the 1960s, Wiskemann in Hamburg,
Germany, had constructed a phototherapy system with Osram
Ultravitalux lamps and another with fluorescent UVB tubes.
10
Photochemotherapy and phototherapy
The revival of photochemotherapy started in 1947 when the
active ingredients of Ammi majus, 8-methoxypsoralen (8-MOP)
and 5-methoxypsoralen (5-MOP) were isolated
11,12
(Fig. 4), and
the first trials with 8-MOP and sun exposure were performed
in vitiligo patients by El-Mofty in Egypt.
13
Later studies used
topical 8-MOP in combination with UV irradiation to treat
psoriasis.
14
The first oral use of 8-MOP to treat psoriasis was
reported in 1967.
15
In 1972 Mortazawi used so-called black-
light UVA tubes in a total-body-irradiation unit with topical
8-MOP to treat psoriasis.
16
However, the UVA output of these
tubes was insucient when 8-MOP was administered orally.
In the 1970s, lighting engineers, photophysicists, and
dermatologists worked together to develop ultraviolet irradia-
tors emitting high intensity UVA. These UVA irradiators were
designed for oral psoralen photochemotherapy to deliver
uniform high dose UVA irradiation. The seminal publication of
Parrish, Fitzpatrick, Tanenbaum, and Pathak reported the use
of this new type of UVA tube in combination with oral 8-MOP
in the treatment of psoriasis.
17
This approach was much more
eective than the blacklight method and represented the real
start of PUVA therapy. The term PUVA was coined by Fitzpatrick
as an acronym for psoralen and UVA (Fig. 5). The eectiveness
of PUVA was confirmed by well controlled clinical trials in
thousands of patients, both in the USA and in European
countries
18
(Fig. 6). Combination therapy with oral retinoids
and PUVA contributed to greater eectiveness and long-term
safety of psoralen photochemotherapy.
19
The use of psoralen
baths and subsequent UVA exposure (bath PUVA) originated in
Fig. 1 Nils Ryberg Finsen (18601904) (Courtesy of the Clendening History of
Medicine Library, University of Kansas Medical Center.
Fig. 2 Lupus vulgaris treatment at the Finsen Institute in Copenhagen
(Courtesy of Prof. Hans Christian Wulf, Copenhagen).
Fig. 3 William H. Goeckerman (18841954) from: www.psoriasiscouncil.org/
publications/slide_library/66.
Photochemical & Photobiological Sciences Perspective
This journal is © The Royal Society of Chemistry and Owner Societies 2013 Photochem. Photobiol. Sci., 2013, 12,1621 | 17
Scandinavia and is still in use as it avoids 8-MOP side eects
such as nausea and dizziness.
20
PUVA revolutionized dermatological therapy and it became
a standard treatment for many skin diseases. PUVA in fact was
the driving force in the mid-70s that sparked a whole new
series of discoveries during the next two decades i.e. newly
created high intensity ultraviolet sources such as narrowband
UVB, and later UVA1 (340400 nm).
As mentioned above, it was the development of PUVA that
led to the discovery of narrowband UVB (311313 nm)
irradiation, which replaced broadband UVB, as the first line
therapy for psoriasis due to being more ecacious. In 1976,
Parrish & Jaenicke defined the action spectrum for psoriasis
with a peak at 313 nm
21
(Fig. 7). However, it took almost a
decade for commercially produced artificial lamps at this wave-
length to be available as narrowband UVB. Van Weelden, Baart
de la Faille, Young and van der Leun in 1984
22
demonstrated
the clinical ecacy of narrowband UVB (Fig. 8) which was con-
firmed a few months later by Green et al.
23
Since then, it has
Fig. 4 Ammi Majus (Deutschlands Flora in Abbildungen (1796). From: www.
BioLib.de.
Fig. 5 Thomas B. Fitzpatrick, Edward Wigglesworth Professor of Dermatology,
(19192003) (Courtesy of Klaus Wol MD).
Fig. 6 First PUVA unit in Vienna 1975 (Courtesy of Herbert Hönigsmann MD).
Fig. 7 John A. Parrish, Professor of Dermatology emeritus (Courtesy of Herbert
Hönigsmann MD).
Perspective Photochemical & Photobiological Sciences
18 | Photochem. Photobiol. Sci., 2013, 12,1621 This journal is © The Royal Society of Chemistry and Owner Societies 2013
proven to be more eective than broadband UVB and is
increasingly used in various parts of the world. It is also ben-
eficial for a variety of other dermatoses that were previously
treated with PUVA. The use of PUVA nowadays has declined
with the emergence of narrowband UVB because of its easier
handling. Another reason may be the increased risk of skin
carcinoma after excessive exposures. Exposure to more than
350 PUVA treatments greatly increases the risk of squamous
cell carcinoma (SCC), whereas exposure to fewer than 150
PUVA treatments has, at most, modest eects on SCC risk.
24
So
far this risk has not been shown with narrowband UVB.
25
PUVA, however, still remained the gold standard for comparing
with other phototherapeutic modalities and serves an impor-
tant therapeutic role in cases of dermatoses recalcitrant to con-
ventional phototherapy and in dermatoses that penetrate
deeper into the skin such as plaque stage mycosis fungoides.
These eective therapiesPUVA and narrowband UVBfor
psoriasis have been a boon for the patients with generalized
psoriasis, providing ecacious ambulatory treatments
and avoiding the systemic problems of methotrexate and
cyclosporine.
In 1992, UVA1 (340400 nm) was introduced first for the
treatment of atopic dermatitis. UVA1 penetrates deeper than
UVA2 (320340 nm) and thus is able to reach deep dermal
components of the skin.
26
A few studies with small numbers
of patients showed ecacy in some other dermatoses such
as localized scleroderma, urticaria pigmentosa and mycosis
fungoides. The published evidence on how best to use
UVA1 has still remained limited and of variable quality. UVA1
is eective in various diseases, but appears to be the first-line
phototherapy only for some types of sclerosing diseases such
as morphea.
27
In the early 1980s a new form of phototherapy, namely,
extracorporeal photochemotherapy (photopheresis, ECP) was
introduced for the palliative treatment of erythrodermic
cutaneous T-cell lymphoma (CTCL).
28
Its ecacy was con-
firmed later by several uncontrolled clinical trials and
approved as a device in 1988 by the FDA for the treatment of
this disease. In 1994, at the International Consensus Confer-
ence on Staging and Treatment Recommendations for CTCL,
ECP was recommended as the first-line of treatment for
patients with erythrodermic CTCL.
29
Meanwhile, besides CTCL, ECP also plays an important role
in the treatment of chronic GVHD after allogeneic bone
marrow transplantation with excellent response rates.
30
In
addition, positive results have also been published for acute
GVHD.
31
ECP has also been used in several other autoimmune
diseases including acute allograft rejection among cardiac,
lung and renal transplant recipients and Crohns disease, with
some success.
32
Photodynamic therapy
At the beginning of the 20th century, the first experiments
were performed with photosensitizers and visible light in the
treatment of skin cancer, which is now known as photo-
dynamic therapy (PDT). While studying the eects of acridine
on paramecia cultures, Oscar Raab, a student of Hermann von
Tappeiner in Munich observed a toxic eect. Fortuitously,
Raab also observed that light was required for the killing of
paramecia cultures to take place.
33
Subsequent work in the lab-
oratory of von Tappeiner showed that oxygen was essential for
the photodynamic action”—a term coined by von Tappeiner
34
(Fig. 9).
Fig. 8 Jan C. van der Leun (Photo taken at the Fifth Ministerial Conference on
Environment and Development in Asia and the Pacic, 24 March 2005).
Fig. 9 Hermann Tappeiner, Edler von Tappein (18471927). © Ludwig-Maximi-
lian University, Munich.
Photochemical & Photobiological Sciences Perspective
This journal is © The Royal Society of Chemistry and Owner Societies 2013 Photochem. Photobiol. Sci., 2013, 12,1621 | 19
With the discovery of photodynamic eects, von Tappeiner
and colleagues went on to perform the first PDT trial in
patients with skin cancer using the photosensitizers eosin
and Magdala-red solution. Out of 6 patients with a facial basal
cell carcinoma treated with the dyes and exposure either to
sunlight or to arc-lamp light, 4 patients showed total tumor
resolution and a relapse-free period of 12 months
35
(Fig. 10).
Although they reported this success, it would take most
of the 20th century to verify the utility of photodynamic
therapies until Thomas Dougherty and co-workers at Roswell
Park Cancer Institute, Bualo NY, clinically started PDT again.
In 1978, they published impressive results in which they
treated 113 cutaneous or subcutaneous malignant tumors and
observed a total or partial resolution of 111 tumors
36
(Fig. 11).
The photosensitizer used in the clinical PDT trials by
Dougherty was an agent called hematoporphyrin derivative
(HpD) which was applied intravenously. However, the problem
with this route of administration was that the whole skin
became photosensitized for up to 6 weeks.
The milestone for PDT in dermatology was the observation
of Kennedy, Pottier and Pross that topically applied 5-aminole-
vulinic acid would induce tissue accumulation of protopor-
phyrin IX (PPIX) in skin tumors. PPIX acted as an endogenous
photosensitizer and upon illumination with red light destroyed
tumor tissue.
37
The major advantage of this regimen was that
the patients skin was sensitized only in the desired area.
Besides 5-aminolevulinic acid, methyl-aminolevulinate
(MAL) produced commercially under the name Metvix® is now
quite commonly used with similar success. PDT has become a
routine treatment for widespread actinic keratosis, superficial
basal cell carcinoma and Bowens disease.
38
New sensitizers
are now tested for other dermatological conditions such as
psoriasis, however no major breakthrough has been reported
so far.
The successful use of the new ultraviolet and light tech-
niques for the treatment of disease was a stimulus for the
development of a new sub-specialty called photodermatology,
which encompasses all of the applications of the diagnosis
and treatment of light-induced disorders as well as the use of
the new modalities for therapy of diseases. There now exists
both national and international Photomedicine Societies as
well as specialized journals of photodermatology. According to
a quote by Kendric C. Smith,
39
one of the founding fathers of
the American Society for Photobiology, I would like to close:
PhotodermatologyThe Future is Bright.
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Photochemical & Photobiological Sciences Perspective
This journal is © The Royal Society of Chemistry and Owner Societies 2013 Photochem. Photobiol. Sci., 2013, 12,1621 | 21
... Heliotherapy has been a therapeutic method used in the treatment of various medical conditions for >3,500 years (1). At the beginning of the 20th century, this method was considered to be revolutionary in the treatment of pulmonary tuberculosis, arthritis and small pox, the first dermatological indication being lupus vulgaris (cutaneous tuberculosis) (1). ...
... Heliotherapy has been a therapeutic method used in the treatment of various medical conditions for >3,500 years (1). At the beginning of the 20th century, this method was considered to be revolutionary in the treatment of pulmonary tuberculosis, arthritis and small pox, the first dermatological indication being lupus vulgaris (cutaneous tuberculosis) (1). The evolution of modern phototherapy has led to an improved understanding of the ultraviolet (UV) radiation effects. ...
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Since the introduction of modern phototherapy in 1903 by Nobel Prize-winner Niels Ryberg Finsen, the usage of this therapy in the medical field has grown, techniques have been refined and developed, and it has gained widespread acceptance. Psoriasis vulgaris, parapsoriasis, lichen planus, atopic dermatitis, neonatal jaundice, urticaria, morphea, vitiligo, granuloma annulare and cutaneous T cell lymphoma are only a few dermatological indications that come along with satisfactory results. Most often, it is a 2nd or 3rd line therapy being an alternative in more severe or refractory diseases. Despite the side effects that may occur after phototherapy, which are often minor, the benefits can be significant. Unfortunately, the absolute contraindications limit the use of this type of treatment and implicitly the management of these patients. The current review aimed to combine the recommendations of phototherapy in dermatology, the types of phototherapy that can be suitable for certain dermatological diseases and to emphasize its importance in certain conditions that are associated with significant remission rates.
... The principle was applied to photoinduced tumor cell death by von Tappeiner shortly after [22]. Historical perspectives on antimicrobial PDI (sometimes also termed antimicrobial photodynamic therapy, aPDT) and the related photodynamic therapy of cancer (usually referred to as PDT) are available in the literature [23][24][25]. Although different acronyms are found in the literature, we will consistently use the term antimicrobial PDI in this review, when referring to the light induced photoinactivation of microorganisms treated with exogenous PS molecules. ...
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... The use of sunlight exposure to treat various diseases such as skin diseases, diabetic ulcers, and epithelioma has been traced back to 3000 B.C. [1,2]. The modern use of light in a medical treatment known as phototherapy is producing a successful result in cancer treatment. ...
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Phototherapy is the use of sun light or light from other sources for therapeutic purposes. It is conventionally used for treating several medical conditions like Psoriasis, Vitiligo, Atopic dermatitis, Lichen planus, Alopecia areata, Urticaria pigmentosa, Acne vulgaris and Neonatal jaundice etc. It involves the use of fluorescent light bulb, sunlight and light emitting diodes to treat above mentioned medical conditions. The phototherapy is being used since time unknown to treat different diseases but in modern era different techniques like PUVA, electric light bulb and electric generators and various other light sources are also being used. And it's gaining more importance in treating dermatologic disorders with non-infectious etiology. William Henry Goeckerman use phototherapy to treat Psoriasis in 1923. The phototherapy is not only suggested by modern physicians but also used by unani physicians for the purpose of treating different diseases. In this paper we are trying to explore some disease conditions in which phototherapy is being used for treatment purpose successfully.
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• Photochemotherapy denotes a therapeutic approach that is based on the interaction of light and a photoactive drug. This study describes the efficacy of photochemotherapy, using orally administered methoxsalen and long-wave ultraviolet light in 91 patients with severe, generalized psoriasis. Oral administration of methoxsalen was followed by exposure to a high-intensity long-wave ultraviolet light source, emitting a continuous spectrum between 320 and 390 nm (peak, 365 nm) and an energy of 5.6 to 7.5 mw/sq cm at 15 cm. There was complete clearing of 82 patients (90%), a 90% to 100% clearing in seven (8%), and a satisfactory improvement in two (2%). A paired comparison study in 54 patients showed photochemotherapy to be far more effective than ultraviolet light emitted by fluorescent bulbs or a xenon source. Eighty-five percent of the patients receiving outpatient maintenance treatment have remained in remission for periods up to 400 days. (Arch Dermatol 112:943-950, 1976)
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