Phototesting involves exposing an area of skin to a known dose of UV or visible light and then observing, recording, and interpreting the response (erythema, whealing, or pigmentary changes) at the irradiated site after a pre-established time (generally 24 hours).

The threshold above which different biologic responses are triggered is established by exposing the individual to incremental doses of light radiation. Measures include minimal erythema dose (MED), minimal urticaria dose (MUD), immediate pigment darkening, and minimal tanning dose. These last 2 measures are not widely used in clinical practice, but they do have experimental value and are also used to determine the sun protection factor of sunscreens.

Phototesting has a range of clinical applications.

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  Diagnosis. The phototest is used to confirm a diagnosis of solar urticaria, systemic phototoxicity, or photosensitivity (reduced sensitivity threshold to light) in certain idiopathic photodermatoses, such as chronic actinic dermatitis (CAD). It can also help to characterize certain secondary photodermatoses induced by endogenous agents, such as erythropoietic protoporphyria or photosensitive forms of lupus erythematosus (lupus tumidus and subacute cutaneous lupus erythematosus).

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  Therapy. The phototest is used to calculate the starting dose (30%-70% of MED) for desensitization therapy in photodermatoses.

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  Prognosis and response monitoring. The phototest can also be conducted at different points throughout the course of a disease to monitor response to treatment, for example, to assess changes in photosensitivity in patients with solar urticaria undergoing phototherapy or immunomodulator therapy.

Phototests should preferably be performed on parts of the body that are not usually exposed to the sun. The test site recommended by the Spanish Photobiology Group (GEF) is the lower back and buttock area, although some authors consider the abdomen or the inner aspect of the arm or forearm to be acceptable. Antihistamines and nonsteroidal anti-inflammatory drugs (NSAIDs) must be withdrawn at least 2 days before the test; corticosteroids, psoralens, chlorpromazine, and high-dose vitamins a week beforehand; and chloroquine and immunosuppressive medication at least a month beforehand.

The MED for a given wavelength in the UV spectrum is the minimum dose of radiation (J/cm2) needed to induce erythema (Fig. 1). Because UV-B radiation provokes erythema, the MED always refers to the erythemal response to UV-B unless otherwise specified. Clinical skin abnormalities induced by UV-A radiation are considered to be abnormal responses to UV-A light. Erythematous reactions are generally evaluated by the naked eye, but more objective methods, such as laser Doppler perfusion imaging, may be needed in lesions with diffuse or indistinct borders.1

Figure 1.

Phototest. Minimal erythema dose (MED) for UV-B radiation.

Erythematous response. MED determined using a fluorescent lamp with 5 test fields and a filter to determine the exposure dose according to skin contact time (Gigatest UVB, Medisun).

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Because practically 100% of effective erythema-producing radiation is UV-B radiation, broadband fluorescent UV-B lamps are generally used for phototesting. However, while these lamps offer stable output, are simple to use, and are relatively cheap, their spectral region is far from that of natural sunlight. Solar simulators offer the best spectral match in this respect because, when fitted with appropriate interference filters, they closely approximate natural light. The erythemogenic effect of solar UV-A radiation can also be measured with filters that block wavelengths under 315 to 320 nm. Fluorescent light kits that emit UV-A light do not generally produce sufficient radiation to provoke erythema, unless the patient has a considerably reduced threshold to this portion of the spectrum, as occurs in certain phototoxic reactions. It is therefore advisable to use a monochromator, if available, to test sensitivity to UV-A light. Note that any skin reaction to visible light from any source is abnormal.

The MUD is the minimum dose of radiation needed to produce a wheal located exclusively or predominantly in the irradiated field. It must be accompanied by a reference to the action spectrum: UV-B, UV-A, visible, or infrared light, or a combination of these (Fig. 2). Irradiation doses from visible or infrared light sources cannot be measured in J/cm2. Unlike MED responses, MUD-provoked reactions generally appear several minutes after exposure and last for between 30 and 90 minutes. Inhibition spectra can result in delayed reactions, with wheals sometimes appearing after several hours.

Figure 2.

Minimal urticaria dose (MUD) in a patient with solar urticaria.

Whealing response. MUD determined using a fluorescent lamp with 5 test fields and a filter to determine the exposure dose according to skin contact time (Gigatest UVB, Medisun). (Photograph courtesy of Dr Diego de Argila, Hospital La Princesa, Madrid, Spain).

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The phototest in patients with solar urticaria is in the strictest sense a photoprovocation test. Standardization is difficult because of the variability of individual factors (phototype, tanning ability, test site, or food-related factors such as colorants). To determine the action spectrum, the European Dermatology Forum recommends using a solar simulator or a monochromator to irradiate 3 different sites in the buttock area with 6J/cm2 of UV-A light, 60 mJ/cm2 of UV-B light, and visible light from a slide projector for 10 minutes. The reaction is scored on a 6-point scale, where 0 indicates no response; (+), just perceptible erythema (corresponding to the MUD); +, erythema in the irradiated area; ++, erythema outside the irradiated area; +++, wheal in part of the irradiated area; and ++++, wheal in the entire irradiated area. The MUD is determined by irradiation with incremental doses of radiation.

Photoprovocation consists of repeatedly exposing an area of skin to a pre-established dose of radiation of a shorter or longer wavelength with the aim of reproducing the clinical lesions being investigated. The test should be performed on a part of the body that is generally not exposed to sunlight. The test field should be larger than that used in phototesting, as photoprovocation sometimes induces separate papules and the response could be underestimated if smaller fields are used. The recommended size is 5×8cm.

The following photoprovocation protocol has been proposed for polymorphic light eruption (PLE): irradiation of a previously exposed area of skin measuring 5×8cm for 3 consecutive days with polychromatic UV-A light at a dose of 60 to 100J/cm2 (Fig. 3) and polychromatic UV-B light at a dose of 1.5 times the UV-B MED, with reading of results at 24 and 72 hours.2 Other authors have successfully provoked lesions on the arms of patients with PLE using lower UV-A doses (10-20J/cm2 for 4 days) and narrowband (NB) UV-B therapy (0.4 and 0.8J/cm2 for 2-4 days). They used fluorescent UV lamps fitted in a cylindrical device into which the patients’ arms were placed.3 It is important to distinguish between PLE lesions and erythema when using UV-B radiation. The best time of the year for photoprovocation in PLE is early spring, before patients are exposed to the intense summer sun.

Figure 3.

Photoprovocation.

Photoprovocation with repeated doses of UV-A radiation applied to the back of a patient with polymorphic light eruption. (Photograph courtesy of Dr. José Aguilera, Faculty of Medicine, Universidad de Málaga, Málaga, Spain).

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The recommended protocol for CAD is irradiation of an unexposed area of skin (5×8cm) for 3 consecutive days with UV-A light (doses of 0.5, 1, 5, 10, 20, and 30J/cm2) and UV-B light (doses of 0.5, 1, and 1.5 times the UV-B MED); results should be read at 24, 48, and 72 hours and after a week.2 Photoprovocation tests should preferably precede any photopatch tests. It should be noted, however, that photoprovocation is often not necessary in CAD, as phototests generally produce clear results: very low MEDs and abnormal UV-A responses.

Photoprovocation results vary greatly from one series to the next. This variability, combined with the fact that the test is laborious and time-consuming, means that photoprovocation is of limited clinical value. It can, however, be useful in cases of PLE with an unclear clinical history or in photosensitive forms of lupus erythematosus.4

Photopatch testing is performed when the patient's history and the physical examination suggest a photosensitivity disorder in which various exogenous chemical substances may be involved. This test is indicated in the diagnosis of photoallergic contact dermatitis and the evaluation of certain idiopathic photodermatoses (e.g., CAD) or photodermatoses that cannot be explained by the patient's history.

Photopatch tests are generally used in photobiology and contact dermatology units.5 The methods employed vary considerably between centers, with variations in allergens, vehicles, concentration, occlusion time, dose and type of radiation, time of readings, and interpretation of results. In 2002, a panel of European dermatologists and photobiologists met with the aim of standardizing most of these variables to facilitate the comparison of results between centers.5 However, the allergens and allergen concentrations used in different photopatch series vary with the geographical area and their inclusion depends on the frequency of sensitization in the population. Numerous photopatch studies have been undertaken in recent years to identify and determine the frequency of photoallergens.6–12 In a publication reporting the results of a photoallergen study in Spain, the Spanish Photobiology Group agreed to add most NSAIDs and UV filters marketed in Spain to the next baseline photopatch series.13 A subsequent European multicenter study confirmed that the European baseline photopatch series should also include UV filters and NSAIDs.14

Currently, the phototest technique consists of the occlusive application of duplicate sets of allergens on the patient's back (normally the upper back, next to the spine) for 2 days. The allergens can be attached using a range of patch devices. On day 2 (48hours), the patches are removed and any skin reactions observed are noted. One of the allergen sets is then covered with an occlusive dressing and the other is irradiated with 5J/cm2 of UV-A radiation, measured using a radiometer. In patients with CAD, it may be necessary to irradiate the area with a suberythemal UV-A dose to avoid confusion with abnormal reactions to UV-A radiation. The results are read for a second time on day 4 (2 days after irradiation) and scored using the International Contact Dermatitis Research Group scoring system (Table 1). If the results are unclear on day 4, another reading is made on day 7.15

Important factors in photopatch testing are irradiation dose, occlusion time, and type of lamp. This last factor has been shown to affect results.8 An ideal light source should have a continuous emission spectrum in the UV-A range (320-400nm) and sufficient irradiance to generate 5 to 10J/cm2 in a reasonable time (several minutes).16 One study that analyzed 3 light sources with different emission spectra used in photopatch testing showed that the broadband UV-A lamp had the highest sensitivity.17 A later study confirmed that UV-A irradiation results in more positive reactions.15

Photopatches have traditionally been irradiated 48 hours after occlusion in contact dermatitis units and 24 hours after occlusion in photobiology units. An occlusion time of 48 hours has been shown to be associated with a higher rate of detection of photoallergy cases.18

Most studies use an irradiation dose of between 1 and 10J/cm2, although some authors have recommended 5J/cm2 for photopatch testing.19,20 In 2004, following the recommendations of the European Task Force for Photopatch Testing, the Spanish Photobiology Unit established an irradiation dose of 5J/cm2.13 In a recent study, Kerr et al.14,59 obtained a much higher percentage of positive results with 5J/cm2 than with 2.5J/cm2. Accordingly, in the absence of contraindications, a dose of 5J/cm2 should be used.

The optimum concentration for UV filters in photopatch testing has been established in recent years. Most filters are tested at a concentration of 10% in petrolatum. Benzophenone-4 should not be used at a concentration of more than 2% in petrolatum because of the risk of false positives.21 However, studies of sunscreens have shown that most skin reactions are elicited by the irritant effects of filters and excipients.22,23

Table 2 shows the expected results of photobiologic tests for a range of idiopathic photodermatoses.

Phototoxic reactions can be diagnosed by phototesting both during and after the use of the causative agent. The normalization of a low MED on withdrawal of a suspected drug confirms a diagnosis of phototoxicity and enables identification of the cause in patients taking multiple drugs. The tests should be performed in a lesion-free (unexposed) area. Patients typically have very high sensitivity to UV-A radiation (and much less frequently to UV-B radiation) while taking the drug, but this normalizes several days after withdrawal.

Photopatch tests should be performed in patients with suspected phototoxic and photoallergic reactions (Fig. 4). The results should be interpreted as follows8,10:

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  Positive patch test on irradiated side and no reaction on nonirradiated side: contact photoallergy

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  Positive patch test on irradiated and nonirradiated sides: contact allergy

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  No reaction on either side: negative result

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  Stronger reaction on irradiated side than on nonirradiated side: photoaggravated contact allergy

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  Weaker reaction on nonirradiated side than on irradiated side: photoinhibited contact allergy

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  Reaction with a morphologic pattern and time course typically seen in skin irritation: irritant reaction

Figure 4.

Photopatch test.

Panel of UV filters and fragrance mix I components. Allergic contact photodermatitis due to nonsteroidal anti-inflammatory drug: positive photopatch test to ketoprofen. The reaction to octocrylene (UV filter series) in the nonirradiated patch set is probably an irritant reaction and the negative result in the irradiated patch set might be due to an inhibitory UV-A effect.

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One group of authors described 4 morphologic phototest patterns to aid in the distinction between photoallergic and phototoxic reactions. The patterns were a classic photoallergic crescendo pattern, an immediate reaction with a decrescendo pattern (phototoxicity), a plateau pattern, and a combined pattern with an immediate and delayed reaction of unknown origin.53

Finally, it is essential to determine the relevance of all positive photopatch test results within the context of the patient's history, the presence of the allergen, and the existence of a temporal relationship between UV exposure and onset of photosensitivity. The most common photoallergens identified in the 1960s and 1970s were halogenated salicylanilides and chlorinated phenols (fenticlor), used as antibacterial agents in soaps. Musk ambrette was withdrawn from the market several years ago, but this fragrance is still an ingredient in products imported from Asia54 and therefore might be relevant in cases of contact photoallergy.

The prevalence of positive photopatch test results is currently low.5,13,53 UV filters8 and NSAIDs9 are the most common allergens involved in photoallergic contact dermatitis, followed by fragrances,10 promethazine,11 and certain plants.48,55 Ketoprofen tops the list of photoallergens in Spain, followed at quite a distance by benzydamine and etofenamate.13 Fragrance mixes tend to cause contact rather than photoallergic reactions. Photoallergy to ketoprofen is also common in other countries, such as Belgium56 and Sweden57; the prevalence of this photoallergen has been attributed, at least in part, to prescribing habits and the drug's photosensitizing capacity.58 Ketoprofen cross-reacts with benzophenone-3, cinnamic aldehyde (fragrance mix component), and phenofibrate.56,57 According to a European multicenter study published in 2012, ketoprofen, etofenamate, octocrylene, and butyl methoxydibenzoylmethane were the most common chemical substances involved in contact photoallergy.14

Exposure to small doses of UV radiation induces a certain degree of natural sun protection. Photoadaptation, or UV hardening, is also used as prophylactic treatment in photodermatoses and photosensitivity. Its use in PLE and solar urticaria is well established.

The mechanism underlying UV hardening is unknown, but it is thought to possibly involve increased melanin synthesis, a thickening of the stratum corneum, a decrease in the hypothetical antigen, or a combination of these factors. However, immunologic mechanisms certainly also have a role. UV radiation has been shown to induce changes in Langerhans cells and other inflammatory skin cells such as lymphocytes, macrophages, and neutrophils.

In patients about to start UV hardening therapy, photobiologic studies are necessary in order to establish the starting dose and subsequent increments (by determining degree of photosensitivity).

The authors declare that the procedures followed complied with the ethical standards of the corresponding human experimentation committee and the World Medical Association and with the principles of the Declaration of Helsinki.

The authors declare that they have followed their hospital's protocol on the publication of data concerning patients and that all patients included in the study have received sufficient information and have given their written informed consent to participate in the study.

The authors obtained informed consent from the patients and/or subjects referred to in this article. This document is held by the corresponding author.