photosensitivity in lupus erythematosus
TRANSCRIPT
School in photodermatologySection Editor: Rik Roelandts
Photosensitivity in lupus erythematosus
Noah Scheinfeld, Vincent A Deleo
St-Lukes Roosevelt Hospital Center, New York, NY, USA
Background: Lupus erythematosus is a systemic
disease process that may manifest with a variety of
internal and cutaneous findings. Photosensitivity is one
the most common manifestations of lupus erythema-
tosus. In patients with lupus erythematosus, there is a
relationship between exposure to ultraviolet light,
autoantibodies, genetics and other factors in the
development of photosensitivity.
Methods: Literature was reviewed on the topics of
lupus erythematosus and photosensitivity discussed
together and separately. The suggested mechanisms
for their relationship were reviewed and analyzed.
Results: Photosensitivity’s relationship to and influ-
ence on the systemic manifestations of lupus remain to
be defined. Mechanisms for photosensitivity might
include: modulation of autoantibody location, cyto-
toxic effects, apoptosis induction with autoantigens in
apoptotic blebs, upregulation of adhesion molecules
and cytokines, induction of nitric oxide sythase
expression and ultraviolet-generated antigenic DNA.
Tumor necrosis factor a also seems to play a role in
the development of photosensitivity.
Conclusion: The basis for photosensitivity in lupus has
yet to be fully defined. It is more commonly associated
with subacute and tumid lupus erythematosus than
with other variants. Anti-Ro antibodies appear to
relate to photosensitivity. Tumor necrosis factor apolymorphisms appear to be important in some
variants of lupus with photosensitivity. There is no
sin que non antibody or mutation of photosensitivity in
lupus. In patients with lupus, more work needs to be
done to define the mechanisms of photosensitivity.
Key words: anti-Ro antibody; photosensitivity; sub-
actute lupus erythematosus; systemic lupus erythema-
tosus; ultraviolet light.
Lupus erythematosus (LE) is a systemic disease
process that may involve a variety of internal
and cutaneous manifestations. Photosensitivity is one
of the most commonly expressed of these criteria.
There are several variants of LE. They include:
systemic lupus erythematosus (SLE) discoid lupus
erythematosus (DLE), medication induced lupus,
neonatal lupus, tumid lupus (marked by indurated
erythematous plaques) and sub-acute cutaneous lupus
erythematosus (SCLE). A diagnosis of systemic lupus
erythematosus (SLE) is made based on identifying in
a patient manifestations of at least four of 11 criteria
(Table 1).
The science of photosensitivity began to be defined
in the 1960s and early 1970s. An understanding of
lupus and photosensitivity benefited initially from the
work of Baer and Harber (1) and Everett and Olson
(2). Tan (3) was the first to detect ultraviolet (UV)-
altered DNA. Cripps and Rankin (4) helped to define
the action spectra of LE and its immunofluorescence.
Freeman et al. (5) investigated the induction by mono-
chromatic light of cutaneous lesion of LE. The contri-
butions of these researchers has been built upon in the
last four decades although many questions remain.
What are the cutaneous manifestations oflupus?In SLE, primary lesions include confluent erythema,
edema and erythematous macules and papules espe-
cially on the malar eminences and the nasal bridge.
Bullae can be present as well as morbilliform macules
and papules in a generalized photo-distributed pattern.
In DLE, the primary lesion is an erythematous-brown
papule or plaque with slight-to-moderate scaling,
dilation of follicular openings with keratinous plugs
(termed follicular plugging) and various degrees of
atrophy. In the DLE lesion hypo-, de- and hyper-
pigmentation may be present. The primary lesions of
SCLE are minimally scaly erythematous papules,
Photodermatol Photoimmunol Photomed 2004; 20: 272–279Blackwell Munksgaard
CopyrightrBlackwellMunksgaard 2004
272
which may expand and merge to form either plaques
with scaling in the papulosquamous variant or
annular and/or polycyclic lesions in the annular
variant. Neonatal lupus typically manifests with an
erythematous rash over the face with exaggeration
around the eyes, which is sometimes called ‘owl eyes.’
Any of the skin lesions described above may occur in
LE confined to the skin or may be a part of the multi-
system disease seen in SLE.
What is photosensitivity?Different definitions of photosensitivity in lupus exist.
Millard et al. (6) defines it as an abnormal cutaneous
response to UV radiation. The American College of
Rheumatology explains that photosensitivity is a ‘skin
rash as a result of unusual reaction to sunlight, by
patient history or physician observation.’ It may mean
a sunburn occurring with lower than expected doses
of sun exposure (a decreased minimal erythema dose),
a sensation in the skin of burning, worsening of LE
internal manifestation, or provocation of the skin
manifestations of LE listed above. A patient might
informally define it as some reaction to sunlight,
which they perceive as out of the ordinary. Patients
who have LE sometimes complain that their skin
burns in sunlight with an unusual time course, either
earlier during exposure or in a delayed manner.
The differential diagnosis of photosensitivity is
large and includes genetic and metabolic diseases,
photochemical sensitivity, idiopathic photosensitivity
and other systemic and cutaneous diseases where
photosensitivity is a part of a larger symptom complex
as in LE.
The most common genetic-metabolic disease involv-
ing photosensitivity in the United States is porphyria
cutania tarda. Other conditions include Bloom’s
syndrome, Cockayne’s syndrome, Hartnup disease,
Rothmund–Thomson syndrome, trichothiodystrophy
and xeroderma pigmentosum. Interestingly, some
genetic complement deficiency syndromes mimic
lupus and can manifest with lupus-like symptoms
including photosensitivity. Chemically induced photo-
sentivity includes photo-drug reactions and photo-
irritation and photo-allergic contact dermatitis. The
idiopathic photosensitivities include the most com-
mon of all photosensitivity eruptions, polymorphous
light eruption (PMLE) known by lay-persons as ‘sun
poisoning.’ In fact, the cutaneous reaction of that
condition can be mistaken for LE and many studies
trying to link this common reaction pattern with SLE
have been undertaken with little success. Other rarer
forms of idiopathic photosensitivity include hydroa
vacciforme, actinic prurigo, chronic actinic dermatitis
and solar urticaria. These conditions can be distin-
guished from lupus by clinical history, morphology,
laboratory testing and photo-biologic testing.
What kind of UV light engendersphotosensitivity?The radiation from the sun or artificial sources that is
capable of inducing the skin lesions and systemic
effects in LE is referred to as the ‘action spectrum’ of
the disease. Photobiologists endeavor to determine the
action spectrum for various skin lesions so as to learn
more about the mechanism of the reaction and also so
that strategies can be offered to patients to protect
them against the relevant radiation.
Light or non-ionizing radiation which is produced
by the sun and by artificial sources like indoor lighting
and sun-tan parlor radiation is generally divided into
spectra defined by the wavelength of the radiation.
This includes UV, visible, and infrared radiation
(Table 2).
Most photosensitivity in human skin is caused by
UV radiation and in some rare instances like the
porphyrias, by visible radiation (400–800 nm). UV
Table 1. Criteria for diagnosis of lupus (50)
Malar rash Erythermatous rash on cheeks covering the bridge of the nose
Discoid rash Red or brown plaques sometime with follicular plugging
Photosensitivity Pain or exanthem to exposure with ultraviolet light
Oral ulcers Small erosions on in the nose or mouth
Arthritis Pain in the joints of the hands, arms, shoulders, feet, legs, hips, or jaws. This can be migratory and
accompanied by heat, redness and swelling
Serositis Pleurisy – chest pain or abnormal sounds heard by physician Inflammation of the lining of the heart.
There can be abnormal EKG findings or heart sounds
Renal (kidney) Excessive protein and/or cellular casts in the urine
Neurologic Seizures and/or psychosis
Hematologic (blood) Decrease in red and white blood cells or platelets
Immunologic Immunologic positive anti-DNA test, Ro, La antibody test
Antinuclear antibody (ANA) ANA positive
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Photosensitivity in lupus erythematosus
radiation is classically divided into short-wave UVC
radiation, mid-wave UVB radiation and long-wave
UVA radiation. UVC radiation is made up of
radiation with wavelengths of less than 290 nm. Such
radiation is absorbed by the ozone layer and no UVC
reaches the surface of the earth. UVB radiation, 290–
320 nm, is also called ‘sun-burn’ radiation since it is
the principle cause of inflammation in the skin of
normal persons induced by excessive sun exposure
and is also most responsible for photo-ageing and skin
carcinogenicity. UVA radiation, 320–400 nm, unlike
UVB radiation, penetrates window glass so that
human skin is exposed to this radiation indoors and
while individuals are traveling in automobiles. UVA
radiation is commonly sub-divided into UVA1 340–
400 nm and UVA2 320–340 nm.
One phototesting study noted that skin lesions of
various form of LE could be reproduced experimen-
tally and that the action spectrum of the induced
lesions was within the UVB range in 33% of patients,
in the UVA range in 14%, and in both the UVB and
UVA ranges in 53% (7).
Research in vivo and in vitro has buttressed the role
of UVA and UVB in evoking LE. Cultures of cells
taken from SLE patients showed a decrease of their
unscheduled DNA repair capacity following UVB
irradiation, whereas most controls did not (8). UVA
was involved in the development of lupus in a Swedish
study (9). One report has noted a woman with SLE
who worked as a photocopy technician who deve-
loped cutaneous LE of the hands, neck, face, and
chest. Her skin lesions improved when she discon-
tinued her employment. Testing of several photocopy
devices showed emission of small quantities of UVA,
but not UVB (10). Fluorescent lighting emitting UVB
can also evoke lupus (11). A practical consequence of
UVA sensitivity is that patients with LE are not
adequately protected by glass covers or by conven-
tional sunscreens, which mostly absorb UVB radia-
tion. Moreover, high-intensity UVA sources in
tanning salons might be dangerous for these patients.
Film to cover windows, which absorb or reflect UVB
and UVA radiation can aid LE patients (12).
Unlike the effect of UVB radiation in LE, which is
always believed to be detrimental, the role of UVA in
lupus is complex and may in rare circumstances be
beneficial. McGrath has reported that UVA1 (340–
400 nm) (13) improved lupus disease activity, de-
creased sDNA titers and reduced medication use in 3
weeks. Therapy with visible light had no effect in these
patients (14). In a related study, six patients got long-
term relief with UVA1 used one, two or three times a
week (15). The mechanism of this treatment is uncertain.
Photosensitivity and lupusPhotosensitivity’s relationship to and influence on the
systemic manifestation’s of LE is unclear. Some
patients have noted that sun exposure increases
disease symptoms (including weakness, fatigue and
joint pain). Fluctuation in an individual’s symptoma-
tology related to solar exposure using objective
variables has not been demonstrated in sizeable
cohort studies. Although cutaneous manifestations
of lupus are more common in the summer months,
systemic disease activity is increased in the 3–6
months following maximal potential sun exposure,
suggesting that summer UV light exposure may lead
to systemic flares several months later (16, 17).
SCLEOf particular interest in understanding the relation-
ship of photosensitivity and LE is SCLE. This LE
variant routinely manifests with photosensitivity and
serologically most affected individuals have Ro
antibodies, thought to be a marker for photosensitiv-
ity. SCLE has certain diagnostic criteria (Table 3).
Clinical features most characteristic of SCLE rather
than DLE are superficial, non-indurated, non-scarring
papules, macules and plaques, and a close associa-
tion with sun exposure. Histologic examination
of involved skin demonstrates a sparse, superficial
Table 3. Diagnostic criteria for subacute cutaneous lupus erythema-
tosus (51)
1 Characteristic lesions (scaly papules) in women, typical distri-
bution on sun-exposed areas, facial sparing
2 Extreme photosensitivity, frequent disease exacerbations in
spring and summer
3 Possible induction by drugs (thiazides, terbinafine, piroxicam,
penicillamine, glibenclamide, glyburide)
4 Anti-Ro/SSA antibodies (60 kDa peptide)
5 ‘Dust-like particles’ of IgG deposition in the epidermis
6 Strong association with the A1, B8, DR3 haplotype
7 Mild systemic involvement (especially kidney and CNS involve-
ment)
Table 2. Non-ionizing radiation spectra (nm)
UVC o290
UVB 290–320
UVA 320–400
UVA2 320–340
UVA1 340–400
Visible 400–760
Infrared 4760
274
Scheinfeld & Deleo
infiltrate in SCLE as compared with a denser, deeper
infiltrate in DLE. Direct immunofluorescence shows
particulate epidermal IgG deposition (18). Photore-
production (appearance of LE lesion in irradiated
skin) is significantly more frequent in patients with
SCLE then with SLE (19). Early lesions of SCLE may
be difficult to distinguish from polymorphous light
eruption (PMLE).
SCLE is intimately involved with antibodies to the
Ro antigen (SS-A). They are found in annular SCLE
(90%), papulosquamous SCLE (80–85%), SCLE with
vasculitis, Sjogren syndrome, or C2d deficiency
(495%) and mothers of newborns with neonatal
LE (490%) (20).
It is important to understand Ro/SS-A and La/SS-B,
when studying SCLE and photosensitivity. Ro-SSA is
actually a complex of three proteins referred to as Ro-
60, Ro-52 and calreticulin with respective molecular
weights (kDa) of 60, 52 and 46. Expression of
antibodies against Ro/SS-A is associated with SCLE,
Sjorgen’s syndrome and systemic sclerosis. Ro-60 and
Ro-52 represent the most antigenic polypeptides of
Ro/SS-A. La/SS-B is a protein of approximately
50 kDa. The presence of antibodies against La/SS-B is
frequently associated with neonatal Lupus and SCLE.
The mechanism for the development of antibodies to
multiple antigens in affected individuals is usually
thought to be due to ‘epitope spread’ and the physical
association and similarity of these antigens. Ro itself
is found in the skin of patients with SCLE.
Anti-Ro, however, is not a sin qua non of
photosensitivity. Anti-Ro is not commonly found in
association with DLE. However, photosensitivity can
be found in patients with DLE, especially if general-
ized. Other cases of lupus can manifest with photo-
sensitivity without anti-Ro antibodies. Finally, a
lupus-like syndrome has been reported developing in
mice lacking the Ro 60-kDa protein (21).
Epidemiology of photosensitivity and lupusThe prevalence of photosensitivity in LE is not
uniform worldwide. It appears most commonly in
oriental countries such as China and less commonly in
black African countries (Table 4). Studies have shown
that in most cases the lighter the skin type, the greater
the prevalence of photosensitivity. Interestingly,
blacks have fewer cutaneous manifestations of lupus
and different antibody profiles than whites. In a series
of South African black patients, only 68% had
cutaneous findings (22). Interestingly, photosensitivity
in black Jamaican patients with SLE is not associated
with antinuclear–antibody specificity (23).
What is the mechanism for photosensitivity?A number of theories have been adduced as reasons
for the induction of lupus activity by UV radiation.
They include (1) modulation of autoantigen location,
(2) cytotoxic effects related to autoantigens, (3)
apoptosis induction with autoantigens in apoptotic
blebs, (4) upregulation of adhesion molecules and
expression of pro-inflammatory cytokines, (5) induc-
tion of nitric oxide synthase expression and (6) UV-
generated antigenic DNA.
Modulation of autoantigen location
Evidence exists for the promotion by UV light of the
migration of autoantigens to the cell surface. The
basis and significance of this process is unclear. UVB
but not UVA can induce the expression of Ro/SSA
antigen on keratinocyte surfaces in vitro (24). Golan
et al. (25) found enhanced binding of IgG autoanti-
bodies to the cell surface membrane, RNP, SSA/Ro,
SSB/La and Sm after UVB exposure of cultured
keratinocytes from patients with SLE. Kawashima et
al. (26) found that cellular and cell surface expression
of 46 kDa SSA/Ro (calreticulin) was increased in
response to exposure to UVB. Photosensitivity and
the presence and titers of circulating anti-SS-A/Ro
and anti-SS-B/La antibodies are both directly corre-
lated with the expression of accessible and immuno-
reactive SS-A/Ro and SS-B/La antigens in the skin
specimens of patients with LE (27). How these
antibodies act is uncertain. SSA/Ro, a ribonucleo-
protein antigen expressed on UVB irradiated kerati-
nocytes, may be recognized and presented to immune
cells by a direct cell-cell contact rather than circulated
in extracellular fluids (28).
Cytotoxic effects
Once autoantigens are located on the cell surface, they
can lead to cytotoxic attacks on expressing cells. The
Table 4. Worldwide epidemiological prevelence of photosensitivity
and malar rash in lupus
Photosensitivity
(%)
Malar
rash (%)
Taiwan (52) 90.9 86.1
Puerto Rico (53) 76.9 71.9
Kuwait (54) 48.8.8
United Arab Emirates (55) 40.5 35.75
Tunisa (56) 41 71
Greece (57) 50 37
Pakistan (58) 60
Singapore (59) 30
US, North Carolina – Whites (60) 53 44
US, North Carolina – Blacks 30 35
South African Blacks (61) 19
275
Photosensitivity in lupus erythematosus
subclass bound in the skin in SCLE is IgG1, a
subclass capable of mediating tissue injury via
complement or cellular effectors (29). The comple-
ment membrane attack complex (C5b-9) has been
identified in lesional but not in uninvolved skin of
patients with SLE or SCLE. These findings are
suggestive that the interaction between Ro and
UVB-irradiated keratinocytes can provoke the photo-
senstivitity and cutaneous eruptions in SLE and
SCLE through a cytotoxic mechanism.
Apoptosis induction with autoantigens in apoptotic
blebs
In vitro, UVB-irradiated keratinocytes from normal
individuals actively cleave their DNA and undergo
apoptosis (30) . Cells concentrate autoantigens such as
Ro, during apoptosis, the antigens recognized by
autoantibodies such as Ro/SSA and calreticulin are
concentrated in structures termed blebs or apoptotic
bodies found at the cell surface. Larger blebs arise
from the nucleus and contain Ro/SSA, La/SSB and a
variety of nuclear antigens. It has been suggested that
the bleb-associated antigens may then be phagocy-
tosed, packaged and presented to lymphocytes, there-
by facilitating immunological activation (31).
Apoptosis itself leads to the production of antigens
that autoantibodies target and the large volume of
such antigens might effect the immune system’s self
tolerance. Proteins phosphorylated during apoptosis
may be preferred targets for autoantibody production
in patients with SLE (32). Most autoantigens targeted
across the spectrum of human systemic autoimmune
diseases are efficiently cleaved by granzyme B in vitro
and during cytotoxic lymphocyte granule-induced
death, generating unique fragments not observed
during any other form of apoptosis (33). Recognition
of apoptotically and oxidatively modified forms of the
U1-70-kd autoantigen are associated with distinct
clinical rheumatic disease manifestations (34).
Upregulation of adhesion molecules and cytokines
UV light has manifold effects on adhesion molecule
and cytokine expression and function. ICAM-1, an
adhesion molecule, has increased expression in
keratinocytes exposed to UV light and TNF-a (35).
In SCLE, there is diffuse epidermal ICAM-1 expres-
sion, with occasional accentuation on the cell surface
of basal cells, a pattern induced by UV light, which is
consonant with the release of TNF-a. In vivo, in LE
patients, increased keratinocyte ICAM-1 expression
was found 1 week after UV provocation in biopsies in
cutaneous reactions that eventually developed into
long-standing LE lesions. It is possible that these early
changes reflect an underlying defect in the mechan-
isms that regulate adhesion molecule expression in
LE (36). Aberrant expression of heat shock protein
70 (HSP70) in skin lesions of SLE might contribute
to both skin lesions and antibody formation in SLE
(37). UV light induces the release of pro-inflamma-
tory epidermal and dermal mediators such as IL-1
and TNF-a that are thought to be involved in the
promotion of lupus as well.
Induction of nitric oxide synthase expression
Aberrant regulation of cytokine-inducible nitric oxide
synthase (iNOS) expression has also been noted in
photo-induced lesions of cutaneous lupus (38).
Healthy controls were shown to have short-term
expression of iNOS after either UVA or UVB
irradiation. The kinetics of iNOS induction as well
as the time span of local iNOS expression may be
critical to the development of cutaneous LE lesions.
Patients with cutaneous LE are noted to have
significantly delayed but prolonged expression of
iNOS. Both IL-1 and TNF-a promote the expression
of iNOS (39) and this abnormal expression in
cutaneous LE could be secondary to a genetic
dysregulation of these cytokines.
UV-generated antigenic DNA
UV light can generate reactive oxygen species in
human tissue. Mammalian experiments demonstrate
that DNA damaged by reactive oxygen species (ROS-
DNA) can be immunogenic. That is, ROS-DNA
inducing antibodies are produced that recognize both
native and ROS-DNA. For example, hydroxyl
radical, generated by UV irradiation of hydrogen
peroxide caused damage to native calf thymus DNA
leading to strand breaks, base modification and
decrease in melting temperature, and such ROS-
DNA was highly immunogenic in goats (40). UV-
altered DNA has also been found in LE patients. The
presence of UV DNA antibodies correlated well with
the presence of native DNA antibodies (41).
TNF-a, SCLE and photosensitivityTNF-a appears to play a key role in the pathogenesis
of SCLE and its concomitant photosensitivity. SCLE
is associated with polymorphism in the TNF allele
(42). Researchers have found an association of the
promoter polymorphism 308A of tumor necrosis
factor a with subacute cutaneous lupus erythematosus
and distinct photoregulation of transcription (43).
Compared with healthy controls, there was a sub-
stantially increased prevalence of 308A polymorphism
276
Scheinfeld & Deleo
in SCLE, an extremely photosensitive form of
cutaneous lupus erythematosus, but not in DLE. Ro
antibodies and nephritis have been associated with
TNF polymorphism (44).
Assessing photosensitivity in lupusPhototesting is a method for assessing the response
of skin to visible and UV light in patients suspected
of having photosensitivity. The skin is exposed to
defined wavelengths of light from various artificial
sources. In most studies of individuals with LE, it
has been necessary to treat the skin with multiples
of the MED (minimal erythema dose) and to do so
repeatedly. This is termed a photoprovocation test.
Test sites are evaluated 24, 48, 72 h and up to
4 weeks after the last irradiation. A follow up of less
than 3 weeks can miss positive results in some
patients. There can be a persistence of hyperpigmen-
tation and hypopigmentation for several months after
irradiation.
Phototesting can reproduce lesions in SLE (25–
85%), SCLE (50–100%), tumid Lupus (70–81%) and
DLE (10–64%). The more widespread the DLE, the
higher the rate the positive phototesting. The high
incidence of positive phototest reactions in correlation
with the clinical findings, history of photosensitivity
and antinuclear antibodies enable the classification of
erythematosus tumidus as the most photosensitive
type of LE (45).
However, phototesting is rarely necessary to make a
diagnosis of photosensitivity associated with the
various forms of LE. Clinical history, physical
examination, skin biopsy for routine histology and
direct immuno-fluorescence and serologic studies are
the standard for diagnosis.
Patient reports of photosensitivity correlate poorly
with results of phototesting using standardized pro-
tocols (46). There is a poor correlation between
personal history of photosensitivity and a decreased
MED. Interestingly, phototesting usually elicits a
papule rather than erythema with a frequency and
nature not unlike PMLE. The incidence of positive
phototest reactions in Oriental patients with LE seems
to be similar to or a little lower than in Caucasians
(47). There was no correlation between a positive
history for UV sensitivity and phototest reactions
(48). Nevertheless, phototesting can be useful to assess
photosensitivity in lupus patients (49). Since it is
possible that photoprovocation testing in individuals
with LE can induce long-standing skin lesions and
may theoretically at least worsen systemic symptoms,
such testing should be undertaken with care.
Millard has noted that the indications for photo-
testing for patients with lupus include:
(1) The objective demonstration of photosensitivity
where there is doubt from the history and where
such a demonstration would support a diagnosis
of lupus where the clinical picture is otherwise
equivocal.
(2) Phototesting can be used to exclude other causes
of photosensitivity in lupus patients, e.g. chronic
actinic dermatitis, solar urticaria and drug-in-
duced phototoxicity. Those conditions tend to
show characteristic phototesting results.
(3) Photo-provocation tests can be a useful research
tool with which to study the immunology of
evolving lesions of lupus-specific skin disease.
Future considerationsThe basis for photosensitivity in lupus has yet to be
fully defined. It is more commonly associated with
SCLE and tumid lupus than with other variants. In
this regard Ro antibodies appear to be important. The
complex effects that UV engenders in the skin
underlie the pathophysiology of photosensitivity of
lupus. TNF-a polymorphism appears to be important
in some forms of LE with photosensitivity. Photo-
sensitivity occurs worldwide but is less common in
those of African decent. A diagnosis of photosensi-
tivity is made based on clinical and physical examina-
tions. Phototesting is an interesting and sometime
helpful modality in assessing photosensitivity and
lupus. Explicating why phototesting fails to replicate
actual photosensitivity will be an important question
to answer. Improved animal models for photosensi-
tivity will help researchers improve our understanding
of photosensitivity. In sum, our understanding of
photosensitivity has increased but many important
questions remain.
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Accepted for publication 11 February 2004
Corresponding author:
Noah Scheinfeld, MD
St-Lukes Roosevelt Hospital Center
1090 Amsterdam Avenue Suite 11D
New York, NY 10025
USA
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