Clinics in Dermatology (2014) 32, 7379

Photodermatoses, including phototoxic and photoallergic

reactions (internal and external)
Zekayi Kutlubay, MD , Ayegl Sevim, MD, Burhan Engin, MD, Yaln Tzn, MD
.
.
Cerrahpaa Medical Faculty, Department of Dermatology, Istanbul University, Fatih, Istanbul, 34098 Turkey

Abstract Photodermatoses are caused by an abnormal reaction mainly to the ultraviolet component of
sunlight. Photodermatoses can be broadly classified into four groups: immunologically mediated
photodermatoses, chemical- and drug-induced photosensitivity, photoaggravated dermatoses, and DNA
repair-deficiency photodermatoses. In this review, we focus mainly on chemical- and drug-induced
photosensitivity, namely, phototoxicity and photoallergy.
2014 Published by Elsevier Inc.

Photosensitivity can be caused by many different topical

or systemic exogenous agents. These agents are usually
compounds with unsaturated double bonds, which absorb
ultraviolet A wavelength energy. Drugs and chemicals that
are most frequently responsible for phototoxic and photoallergic reactions will be discussed briefly. Pathophysiology,
clinical manifestations, and histopathologic investigations of
both phototoxicity and photoallergy are summarized separately. The main differences between these two entities,
including clinical appearance, pathophysiologic mechanisms, and time of onset, will be emphasized.
Photosensitivity is a challenging area of dermatology,
with a wide range of morbidities, both for the physician
and the patient. For the exact diagnosis and precise control
of photosensitivity, a systematic approach is vital.
Avoidance of direct sunlight and sun-tanning facilities, as
well as photosensitizing agents, usage of clothing with
ultraviolet filters, and appropriate sunscreen can all
minimize the risk for photosensitivity effects. A combination of measures, including phototherapy in different
modalities and topical and systemic drugs, can be
beneficial in the management of photodermatoses.
Corresponding author. Tel.: 00902124143000-21546.
E-mail address: zekayikutlubay@hotmail.com (Z. Kutlubay).
0738-081X/$ see front matter 2014 Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.clindermatol.2013.05.027

Introduction
Photodermatoses can be broadly classified into four
groups: immunologically mediated photodermatoses, chemical- and drug-induced photosensitivity, photoaggravated
dermatoses, and inherited disorders with defective DNA
repair or with chromosomal instability.1 Immunologically
mediated photodermatoses are solar urticaria, polymorphous
light eruption, hydroa vacciniforme, actinic prurigo, and
chronic actinic dermatitis.2 This large group of diseases is
also called primary idiopathic photodermatoses, because
these diseases consist of ultraviolet (UV)-induced cutaneous
lesions with an unknown cause. Chemical- and drug-induced
photosensitivity can be caused by topical or systemic
exogenous agents, as is the case in phototoxicity and
photoallergy; these reactions can also be caused by
endogenous agents like in cutaneous porphyrias and
pellagra.1 Photoaggravated dermatoses, or so-called secondary photodermatoses, are the result of increased sensitivity to
UV radiation caused by the underlying disease. Acne
vulgaris, atopic dermatitis, bullous pemphigoid, carcinoid
syndrome, cutaneous T-cell lymphoma, Darier disease,
dermatomyositis, disseminated superficial actinic porokeratosis, erythema multiforme, Grover disease, lichen planus,
lupus erythematosus, pemphigus, pityriasis rubra pilaris,

74

Z. Kutlubay et al.

psoriasis, reticular erythematous mucinosis, rosacea, seborrheic dermatitis, and viral infections are examples of
photoaggravated dermatoses.1,2
Inherited disorders with defective DNA repair mechanisms or with chromosomal instability can be listed as ataxiatelangiectasia, Bloom syndrome, Cockayne syndrome,
Hailey-Hailey disease, Hartnup disease, Kindler syndrome,
Rothmund-Thomson syndrome, trichothiodystrophy, and
xeroderma pigmentosum.3
Photosensitivity is the reaction of skin to exogenous or
endogenous agents.4 These agents are usually compounds with
unsaturated double bonds, which absorb ultraviolet A (UVA)
wavelength energy. Exogenous agents can be used systemically or topically, and cutaneous porphyrias are examples of
photosensitivity induced by endogenous agents.5
Photosensitivity induced by exogenous agents is classified into two groups: phototoxicity and photoallergy
(Table 1). Phototoxicity is a direct tissue injury, caused by
phototoxic agent and radiation, which can be seen in every
individual. In contrast, photoallergy is a delayed-type
hypersensitivity reaction. It is caused by chemicals that are
modified by absorbing photon energy. It does not occur
during the first exposure and has a sensitization phase.
The incidence of photosensitivity is rather low, and
phototoxic reactions are far more common than photoallergic
reactions.2 The prevalence of exogenous drug-induced
photosensitivity is not known, but data from photodermatology referral centers show 7% to 15% for phototoxicity and
4% to 8% for photoallergy.6 In studies performed in the
United States and Europe, the incidence rate of photoallergic
contact dermatitis in patients who are photopatch-tested is
between 1.4% to 12.0%.
Age distribution is rather homogeneous, but for
drug-induced photosensitivity, the elderly population is
more susceptible.6
More than 300 types of medications are responsible for
photosensitivity.7 Among topical phototoxic agents, the
most commonly used ones are fluorescein, fluorouracil,
furocoumarins, retinoids, rose bengal, and tar. For systemic
phototoxic agents, the list is much longer. Many antifungals
Table 1

such as griseofulvin; antimalarials such as chloroquine and

quinine; antimicrobials such as sulfonamides, tetracyclines,
trimethoprim, quinolones, amiodarone, and quinidine; and
diuretics such as furosemide, thiazides, psoralens, and
sulfonylureas can cause phototoxic reactions. The photoallergic chemicals can also be classified into topical and
systemic agents. Topical agents refer mostly to sunscreen
ingredients, such as benzophenones, para-aminobenzoic
acid (PABA) derivatives, cinnamates, and fragrance
chemicals (methyl coumarins, musk ambrette, and sandalwood oil). Surface disinfectants, skin cleansers such as
chlorhexidine, hexachlorophene, pesticides, and topical
nonsteroidal anti-inflammatory agents are also topical
agents. Systemic photoallergens can be listed as griseofulvin, quinolone, quinine, ketoprofen, and pyridoxine.8

Phototoxicity
Pathophysiology
More than one mechanism is usually involved in the
pathophysiology of phototoxicity. A photosensitizer chemical absorbs UVA radiation energy. Before this absorption,
the substance being at its ground state rises to an excited state
molecule, with the effect of UV energy. This excited state
chemical is involved in oxygen-dependent reactions, and at
the end of these reactions cytotoxic injury is observed. These
pathways of reactions can be studied in two major classes:
type 1 and 2 reactions.7
During type 1 reactions, an electron is transferred to the
excited state photo sensitizer, and this reaction results in free
radical formation. These free radicals are involved in
oxidation-reduction reactions and occurring peroxides
cause cell damage.9
Type 2 reactions are, in contrast, energy transfer
processes. Here again, transfer of energy to ground state
oxygen causes oxygen radical formation. These radicals
interact with unsaturated fatty acids, and in the end,

Differences and similarities between phototoxicity and photoallergy

Clinical presentation
Pathophysiology
Histology

Onset and occurrence

Dose
Cross-reactivity
Diagnosis

Phototoxicity

Photoallergy

Sunburnlike reaction, erythema,

edema with vesicles and bullae
Direct tissue injury
Epidermal necrosis, dermal edema
with eosinophilic keratinocytes,
dermal infiltrate of lymphocytes,
macrophages, and neutrophiles
Occurs after first exposure and
starts minutes to hours after exposure
Large doses needed
None
Clinical and phototests

Pruritic eczematous lesions

Type IV delayed hypersensitivity
Spongiotic dermatitis, dermal
lymphohistiocytic infiltrate

No reaction after first exposure,

starts 24-48 hours after exposure
Small doses are enough
Common
Clinical and photopatch tests

Photodermatoses

75

hydroperoxides are formed. These substances eventually

lead to oxidation of lipids and proteins. All these
photodynamic processes are seen in cases of porphyrin-,
quinolone-, nonsteroidal anti-inflammatory drug-, tetracycline-, amitriptyline-, imipramine-, sulfonylurea-, hydrochlorothiazide-, chlorpromazine-, and furosemide-induced
phototoxicities.8
Apart from those chemicals, irradiation of phenothiazines, chlorpromazine, tetracyclines, and quinolones produces stable photoproducts, which are again responsible for
tissue damage.
In one other mechanism, a photosensitizer binds to its
biological substrate with the help of radiation. During this
reaction, an excited state molecule bonds covalently to a
ground state molecule. 8-Methoxypsoralen bonds to the
pyrimidine bases of DNA molecules forming cross-links
between DNA strands.
Biologically active products of complement activation,
mast-cellderived mediators, eicosanoids, proteases, and
polymorphonuclear leukocytes may also take part in
the process of phototoxicity. It is usually the case with
porphyrins, chlorpromazine, and demeclocycline, where
inflammation and inflammatory cells participate in
tissue injury.
Photosensitizer plus electromagnetic radiation also induce
apoptosis, together with cytotoxicity, and this property of the
process is used in clinics to treat premalignant and malignant
skin conditions.

Clinical manifestations
Phototoxicity usually shows its effects minutes to hours
after exposure to the phototoxic agent, UV radiation. The
only exception is psoralen-induced phototoxicity. In that
case, acute response first appears after 24 hours and peaks at
48 to 72 hours. All the symptoms are dose dependent,
meaning they depend on both the dose of the drug that is
used and the dose of the UV radiation to which the individual
is exposed. The clinical picture may vary from a mild or even
asymptomatic phase to a severe sunburn.10 The patient may
report a burning and stinging sensation, especially on areas
of the body that have been exposed to sun, such as the
forehead, nose, V area of the neck, ears, and dorsa of the
hands. Erythema and edema are the characteristic findings.
Pruritus usually accompanies, and in severe reactions even
vesicles and bullae may be seen. In differential diagnosis,
one may easily notice the sparing of areas where UV
radiation has not reached, such as the postauricular areas, the
submental area, the nasolabial folds, and under clothing.
Skin lesions may resolve with different degrees of
hyperpigmentation (Figure 1).4
Pseudoporphyria is a clinical form of phototoxicity. The
most common drug causing this is naproxen. The skin
findings in this phenomenon are similar to those in

Fig. 1 This patient illustrates photodermatitis on the face, neck,

and chest.

porphyria cutanea tarda. It is usually evidence of a severe

phototoxic reaction, with erythema, edema, vesicles, and
subepidermal blisters. Histologic findings and immunofluorescence findings are also indistinguishable from porphyria cutanea tarda. The diagnosis is made considering the
history of sun exposure and chemical use, and most
importantly the normal porphyrin profile, in the case of
pseudoporphyria. Apart from naproxen, other drugs such as
amiodarone, celecoxib, beta-lactam antibiotics, cyclosporine, ciprofloxacin, furosemide, imatinib, oral contraceptives, nalidixic acid, oxaprozin, ketoprofen, mefenamic
acid, tetracyclines, and voriconazole can also induce this
type of reaction.
In the case of voriconazole, especially in immunesuppressed patients and for the usage duration longer than
12 weeks, accelerated photo-induced changes can be seen.
These changes include pseudoporphyria, photoaging,
lentigines, premature dermatoheliosis, and even squamous
cell carcinoma and melanoma in cases of use longer than
12 months.11
Photo-onycholysis can also be observed as a manifestation of acute phototoxicity. Fluoroquinolones, tetracyclines,

76
and psoralens are among the medicines that are reported to be
responsible for this damage. It is the painful separation of the
distal nail from the nail bed, whereas the nail plate focuses
UV energy on the nail bed.8
Blue-gray pigmentation is another clinical form of
phototoxicity. It is usually seen in sun-exposed areas
presumably and is associated with many different drugs
and chemicals.10 Amiodarone, chlorpromazine, clozapine,
imipramine, and less commonly desipramine among tricyclic
antidepressants may cause this type of phototoxicity.
Minocycline, for instance, may result in blue-gray pigmentation of the face, mostly on acne scars, and less commonly
on shins and forearms. In the pathophysiology of this type of
pigmentation, a drug metabolitemelanin complex plays an
important role. In case of argyria exposure, a slate-gray
pigmentation is observed, which involves the nail lunulae,
mucous membranes, and sclerae. In this case, silver granules
produced during a photochemical reaction are deposited in
the dermis.
Telangiectasia on sun-exposed areas can occur as a result,
especially when using calcium channel blockers such as
nifedipine, amlodipine, felodipine, and diltiazem, antibiotics
such as cefotaxime, and the antidepressant venlafaxine.
Phytophotodermatitis (grass dermatitis) is also a particular form of phototoxicity, induced by plant extracts,
especially seen in gardeners or after being in close contact
with plants.12 Striped, sharply delineated erythema corresponding to the trails of grass brushing on the skin is typical
for this type of reaction.2
The course of phototoxicity in most patients is usually
self-limited. The symptoms reduce after discontinuation of
the responsible agent. In some cases, even after the patient
stops taking the drug, the symptoms persist, even for years.
In those cases, chronic actinic dermatitis may develop on the
areas of phototoxicity. The clinical findings can be listed as
primarily pruritus and lichenification, together with secondary excoriation on sun-exposed regions. This type of reaction
is more commonly seen with thiazides, quinidine, amiodarone, and quinine.
With chronic exposure to both chemical agents and UV
radiation, as seen in patients who have received long-term
psoralen + ultraviolet A (PUVA) photochemotherapy, longterm cutaneous effects are seen. Phototoxicity in chronic
exposure is known to affect DNA, which, in turn, causes
premature aging of the skin, lentigines, squamous cell
carcinoma, and melanoma.

Phototoxic agents
Agents, drugs, or chemicals that cause phototoxicity can
either be used topically or systemically. Among topical
agents, fluorouracil and retinoids cause serious UVinduced hypersensitivity because of their irritant effect on
the skin.

Z. Kutlubay et al.
Furocoumarins are also a common causative agent for
phototoxic reactions, especially among those with certain
occupations such as bartenders, chefs, and gardeners, as well
as patients receiving topical photochemotherapy with
psoralens.7 In addition, occupational and medical exposure
to coal tar not only causes phototoxic reactions, but also
increases the risk for nonmelanoma skin cancers.
Most systemic agents produce a sunburnlike reaction,
as well as an eczematous photoallergic response. In almost
all of the agents, the action spectra are in the UVA range.
For porphyrins and fluorescein, the spectra of action are
visible light.
Eculizumab, a humanized immunoglobulin G monoclonal antibody that binds to and inhibits complement protein
C5 and is approved for paroxysmal nocturnal hemoglobinuria, was also reported to cause phototoxic reactions.13

Histopathology
In classic, nonchronic phototoxic reactions, necrotic
keratinocytes, epidermal spongiosis, and dermal edema are
seen. In severe cases, epidermal necrosis is also observed.
A mild inflammatory infiltrate, consisting of neutrophiles,
lymphocytes, and macrophages, is almost always found in
the specimen. In the case of slate-gray pigmentation,
increased dermal melanin together with dermal deposits of
the drug and its metabolite are found. In pseudoporphyria,
dermal-epidermal separation at the lamina lucida level, the
same as porphyria cutanea tarda, is detected. Also at the
dermal-epidermal junction and around the nearby blood
vessels, immunoglobulin deposits can easily be seen. In
the case of lichenoid eruption, findings are similar to those
of lichen planus. Spongiosis, dermal eosinophils, plasma
cell infiltrates, and an increased number of necrotic
keratinocytes and cytoid bodies may help in distinguishing
the two entities.

Photoallergy
Pathophysiology
Photoallergy is a delayed-type hypersensitivity reaction,
occurring in the presence of a photoallergic substance and
UV radiation. The wavelength of the radiation is an
important factor, and for most of the substances, UVA
radiation is necessary.
The photoallergen absorbs UVA radiation, enters an
excited state, and afterward releases energy to the surroundings. During this process, the molecule bonds with a carrier
protein and forms a complete antigen. Halogenated salicylanilides, chlorpromazine, and para-aminobenzoic acid are
thought to be the causes of photoallergy by means of this

Photodermatoses
mechanism. Sulfanilamide and chlorpromazine also form a
stable product after being exposed to UVA radiation, and
then together with a carrier protein form a complete antigen.
After this complete antigen is composed, the mechanism
is similar to contact allergy. Langerhans cells take up the
antigen and process it, and afterward migrate to regional
lymph nodes to present the antigen to T lymphocytes. Then
these activated T lymphocytes start to circulate around the
exposed site and start an inflammatory response, only after
which cutaneous lesions develop.

77

Management of phototoxicity and photoallergy

Symptoms usually occur within 24 to 48 hours after

exposure to the photoallergen and UV radiation. The
symptoms are more prominent in sensitized individuals.
The clinical morphology is identical to that of allergic
contact dermatitis; however, the distribution of the skin
lesions can help in differential diagnoses. In photoallergic
dermatitis, mostly body parts that are prone to sun exposure
are affected. In severe cases, the lesions may also be seen in
covered areas of the body, as well as in sun-exposed areas.
The clinical manifestations usually disappear without any
significant postinflammatory hyperpigmentation.
The most common cause of photoallergy, especially in the
United States and Europe, is sunscreen products. UV filters,
especially benzophenone-3, are the leading cause of
photoallergic dermatitis.14 Also, antimicrobial agents are a
rather common cause. For the topical causative agents,
nonsteroidal anti-inflammatory agents are the leading drugs
responsible for photoallergy. Long-term exposure to chlorpromazine, dioxopromethazine, ketoprofen, musk ambrette,
halogenated salicylanilides, and quinidine, together with
chronic UV radiation, may also cause chronic actinic
dermatitis, as in the case of phototoxicity.

The best set of actions should be identified first to avoid

the causative phototoxic or photoallergic agent; furthermore,
avoiding UV radiation is essential, and sunscreens with
efficient UVA filters should be used regularly.
For symptomatic treatment of acute reactions, topical
corticosteroids are the drug of choice. Antihistamines may
also be helpful. In the case of severe reactions, systemic
corticosteroids can also be used. Short-term usage (prednisone 1 mg/kg) from 1 to 2 weeks can be initiated for acute
and severe exacerbations.15
For patients with slate-gray pigmentation, lichenoid
eruption, pseudoporphyria, and photodistributed telangiectasia, only symptomatic therapy is given. In those cases, it
can take a few months for the condition to be resolved.
After resolution of the acute event, if there is marked
hyperpigmentation, depigmentation methods can be used.
A combination of 0.1% retinoic acid, 5.0% hydroquinone,
and 1% hydrocortisone, or laser therapy can be attempted.2
While handling most photodermatoses, preventive UV
phototherapy or psoralen plus UVA, or both, can be used.
The hardening phenomenon is one of the basic features
of prophylactic phototherapy in photosensitive individuals.
Its mechanism is thought to be about increased melanization, stratum corneum thickening, and depletion of
hypothetical antigens.
In the case of persistence of significant photosensitivity,
low-dose broadband or narrowband ultraviolet B (UVB) or
PUVA therapy two to three times a week may be the
treatment of choice, especially in acquired idiopathic
photodermatoses. The treatment is usually initiated during
spring, and an average of 15 sessions is usually enough to
induce hardening. To maintain this hardening state, patients
are told to expose themselves to midday sunlight for 15 to 20
minutes without sunscreen weekly.

Photoallergens

Sunscreen usage

In case of photoallergy, topical agents are usually the most

common cause of the skin lesions. Sunscreen products, topical
antimicrobials, and topical nonsteroidal anti-inflammatory
drugs are most frequently used in everyday practice.7 Systemic
agents, in contrast, are much less frequent.

On a summers day, the UV energy received (daily dose)

is composed of approximately 3.5% UVB and 96.5%
UVA.11 While choosing the most effective sunscreen for
each patient, identification of the photon wavelength
responsible for inducing the sensitivity reaction is important.
This can often be done by the determination of a minimal
erythema dose (MED) to UVA and UVB radiation.16
UVB and UVA filters are categorized into organic and
inorganic filters. There are many efficient UVB filters, but
only a limited number of organic UVA filters are available,
such as the benzophenones (oxybenzone, dioxybenzone, and
sulisobenzone), butyl methoxydibenzoylmethane (commonly
known as avobenzone), and methyl anthranilate.17 All except
avobenzone are primarily protective only against UVA-2
(320-340 nm), whereas the absorption of avobenzone

Clinical manifestations

Histopathology
Histopathologic findings related to photoallergy are
similar to those of allergic contact dermatitis, as is the
morphologic appearance. Epidermal spongiosis together
with dermal mononuclear cell infiltrates are the typical
histologic features.

78
extends into UVA-1 (340-400 nm). Because avobenzone is
photolabile, degradation occurs rapidly on exposure to
sunlight, and by combining it with photostable UV filters,
such as octocrylene, salicylates, or oxybenzone, it can be
photostabilized. Inorganic sunscreens or physical blockers
are titanium dioxide and zinc oxide, which offer protection
from UVB to visible ranges.18
Sunscreen efficacy is measured first by its sun protection
factor, which is a globally accepted index of protection from
erythema after a single exposure to solar-simulated radiation,
primarily the effect from UVB exposure, and to a lesser
extent from UVA-2.

Differential diagnosis of phototoxicity

and photoallergy
All types of nonspecific dermatitis can be included in
differential diagnosis of photosensitivity. Allergic contact
dermatitis caused by inhaled allergens particularly affects
skin folds such as nasolabial folds and eyelids. These areas
receive very small amounts of UV irradiation; thus, they are
not expected to be involved in photo-induced reactions.
Allergic contact dermatitis can also be seen in the
postauricular region and under the chin, where sun exposure
is unlikely. Both allergic contact dermatitis and irritant
contact dermatitis are observed mainly at sites where direct
contact of the inhalant or contact allergen takes place, either
sun-exposed or sun-protected areas.
Other photodermatoses are also included in differential
diagnoses. In the case of polymorphous light eruption,
symptoms appear a few hours after the sun exposure, and
pruritic papules, plaques, and rare vesicles can be seen. The
lesions usually tend to be observed at sun-exposed sites and
are resolved in a few days.
Lesions of solar urticaria are also found in sun-exposed
areas, typically occurring minutes after sun exposure,
morphologically similar to pruritic urticarial plaques, and
in the end are resolved within a few hours.

Approaching patients with phototoxicity

and photoallergy
While evaluating patients with photosensitivity, a
detailed history including the relationship between eruption
and sun exposure, duration of lesions, effect of windowglass-filtered sunlight, exposure to photosensitizing agents,
family history, age of onset, seasonal variation, and systemic
symptoms is crucial.
A physical examination into the morphology and
distributionspecifically presence of symptoms on the
head, face, neck, arms, legs, and torso, and absence
underneath the chin, lips, nasolabial folds, and postauricular

Z. Kutlubay et al.
areacan provide further diagnostic clues. Advanced tests,
such as antinuclear antibody titers, skin biopsies, phototesting, photopatch testing, and porphyrin levels can also help
in diagnosis.
A history of exposure to known photosensitizers is a risk
factor for identifying the cause. For sun exposure, patients
should be questioned extensively about window-glassfiltered sunlight. UVB radiation is filtered out by window
glass, and phototoxic and photoallergic reactions are
prominently caused by UVA radiation. In addition, examining the distribution of the cutaneous lesions will help both
to distinguish the reaction from other types of dermatitis and
to identify the type of photosensitizer responsible. In the case
of systemic photosensitizers, widespread eruption is usually
observed. With topical photosensitizers, however, lesions are
found in regions that are exposed to both the photosensitizer
chemical and the UV radiation. If there are vesicular and
bullous lesions with severe symptoms and complaints of a
burning sensation, the incidence is probably associated with
phototoxicity, whereas eczematous eruptions with pruritus
usually suggest photoallergy.
In some rare cases, a skin biopsy may be needed for
differentiating the two conditions. Necrotic keratinocytes is a
characteristic feature of phototoxicity, whereas spongiotic
dermatitis is associated with photoallergy.
Phototests and photopatch tests also play an important
role in the evaluation and diagnosis of patients with known
photosensitivity, especially in cases for whom physical
examination and history are not sufficient for making a
decision or for determining the causative agent.15
During phototesting and photopatch testing, the MED
should first be determined. Duplicate sets of photoallergens
are applied symmetrically on the body surface, preferably on
the back, and then covered by an opaque tape.19 Then UVA
radiation is applied, in increasing dosages, and MEDs are
added. The MED for UVA and UVB is defined as the lowest
dose of radiation that produces perceptible erythema
covering the entire irradiated area.1 The MED for UVA
radiation is lower than the normal population in the case of
phototoxicity and photoallergy.15
Phototesting is an important step in the evaluation of the
photosensitive patient. A template with several exposable
windows is used, and the patients back, abdomen, or inner
forearms, where there is no lesion, is exposed to different
doses of UVA, UVB, and visible monochromatic or broadspectrum radiation. Systemic immunosuppressants and
topical agents should be discontinued 2 weeks before
phototesting. The cutaneous response is assessed by
observing immediate urticarial lesions, as in the case of
solar urticaria, and also the MED. Photoprovocation testing
is performed to induce lesions 3 to 4 consecutive days with
exposure to the same site, and within 24 hours, lesions
usually develop.15 Phototesting is the most beneficial in the
diagnosis of idiopathic or immunologically mediated photodermatoses, whereas in porphyrias and genodermatoses, the
test is not as beneficial.

Photodermatoses
Photopatch testing, in contrast, is performed when
photoallergic contact dermatitis is suspected. Two sets of
photoallergen panels are placed on uninvolved sites of the
skin, preferably on the upper back. Because it is a known
fact that photoallergens can also cause contact hypersensitivity, photopatch tests are done in duplicates. One set is
removed after 24 hours and irradiated with UVA of 5 to 10 J
cm. After 48 and 72 hours, both the irradiated and
unirradiated sides are evaluated for a positive reaction,
meaning the presence of erythema, edema, and/or vesiculation. If there is a positive reaction at both sites, it indicates
allergic contact dermatitis, whereas a positive reaction at the
unirradiated site with a stronger reaction at the irradiated site
is interpreted as both allergic contact dermatitis and
photoallergic contact dermatitis. In the case of irritant
dermatitis, an erythema appears with well-defined borders,
and this erythema disappears rapidly.
Photopatch testing is contraindicated in cases of
suspected phototoxicity. Nevertheless, only 10% of patients
undergoing photopatch testing have clinically relevant
positive results.20 Photopatch tests are often negative for
photoallergy with medications delivered by enteral or
parenteral routes, because a specific metabolite is actually
responsible for the occurrence of the cutaneous lesions, not
the medication itself.2
The list of agents used for photopatch tests varies
greatly among countries, but the substances commonly
used can be listed as follows6: tetrachlorosalicylanilide
0.1%, 5-bromo-4-chlorosalicylanilide 1.0%, hexachlorophene 1.0%, bithionol 1.0%, sulfanilamide 5.0%, promethazine hydrochloride 0.1%, chinoidine sulfate 1.0%,
musk ambrette 5.0%, fragrance mix 8.0%, 4-aminobenzoic
acid 10.0%, 2-ethylhexyl-4-dimethylaminobenzoate 10.0%,
1-(4-isopropylphenyl)-3-phenyl-1,3-propandion 10.0%,
4-tert butyl-4-methoxy dibenzoylmethane 10.0%, isoamyl4 methoxycinnamate 10.0%, 2-ethylhexyl-4-methoxycinnamate 10.0%, 3-(4 methylbenzylidene) camphor 10.0%, 2phenyl-5-benzimidazole sulfonic acid 10.0%, oxybenzone
10.0%, and sulisobenzone 10.0%.

Conclusions
Photosensitivity is a challenging area for both the physician
and the patient. For the exact diagnosis and precise control of
the photosensitivity, a systematic approach is vital. Avoidance
of direct sunlight, sun-tanning facilities, and photosensitizing
agents, and the usage of clothing with UV filters and
appropriate sunscreen can all minimize the risk for photosensitivity effects. A combination of measures, including

79
phototherapy in different modalities and topical and systemic
drugs, can be beneficial in managing photodermatoses.

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